OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
FOREWORD INTRODUCTION
2-DIMETHYLAMINOETHYLMETHACRYLATE
CAS N? 2867-47-2
UNEP PUBLICATIONS
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
SIDS Initial Assessment Report
for
SIAM 14
(Paris, 26-28 March 2002)
Chemical Name: 2-Dimethylaminoethyl methacrylate
CAS No: 2867-47-2
Sponsor Country: Japan
National SIDS Contact Point in Sponsor Country:
Mr. Koji Tomita
Ministry of Foreign Affairs, Economic Affairs Bureau, Second International
Organizations Division.
Industry: Mr. Kazuhiro Sugamura
Mitsubishi Gas Chemical Company, Inc.
E-mail: ksugamura@mgc.co.jp
History: This substance was sponsored by Japan under the ICCA Initiative and was
submitted for first discussion at SIAM 14.
Peer Review Process:
The industry consortium collected new data and prepared the updated IUCLID,
and draft versions of the SIAR and SIAP. Japanese government peer-reviewed
the documents, audited selected studies.
Testing: No testing (X) Testing ( )
Comments: The industry contact point is Mr. Kazuhiro Sugamura, Mitsubishi Gas Chemical
Company, Inc. acting on behalf of MADAME (2-Dimethylaminoethyl
methacrylate) Consortium (Consortium members: Atofina, Ciba Specialty
Chemicals Inc., Degussa / Roehm GmbH & Co., Mitsubishi Rayon Co., Ltd.,
Mitsui Chemicals, Inc., Sanyo Chemical Industries, Ltd., SNF S.A.).
Deadline for circulation: 1 Feb. 2002
Date of circulation: 1 Feb. 2002
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
SIDS INITIAL ASSESSMENT PROFILE
2867-47-2
CAS No.
2-Dimethylaminoethyl methacrylate
Chemical Name
CH 3
CH2 = C- C- O- CH2- CH2- N- CH3
Structural Formula
O CH 3
RECOMMENDATIONS
The chemical is currently of low priority for further work.
SUMMARY CONCLUSIONS OF THE SIAR
Human Health
2-Dimethylaminoethyl methacrylate is supposedly metabolized to methacrylic acid and N,N-
dimethylaminoethanol. Then the methacrylic acid may form an acetyl-CoA derivative, which then enters
the normal lipid metabolism. The oral LD50 in rats is greater than 2000 mg/kg. This chemical is
considered to be severely irritating or corrosive to skin and eye. This chemical does not have a
sensitizing potential.
The OECD combined repeated dose and reproductive/developmental toxicity screening test [OECD TG
422] was conducted in rats at doses of 0, 40, 200 and 1000 mg/kg/day administered by gavage. For both
sexes, a clear systemic toxicity was demonstrated only at 1000 mg/kg/day. Late onset of twitching,
chronic convulsion and the suppression of body weight gain were observed. Three females out of 12
died. Histopathological examination revealed degeneration of nerve fibers in the brain and spinal cord,
and hyperplasia of the mucosa, edema and inflammatory cell infiltration in the forestomach in both sexes.
Increases in organ weights without histopathological changes were observed in the kidneys of both sexes,
the livers of males, and the adrenals of females in this group. For the males in this group, BUN was
slightly increased and anemic changes such as decreases in erythrocyte counts, hemoglobin concentration
and hematocrit value, associated with a significant increase in reticulocyte ratio were observed. In males
from the 200 mg/kg/day group, only slight anemic changes such as those observed at 1,000 mg/kg/day
were seen, but the severity was considered toxicologically insignificant. The NOAEL for the repeat dose
toxicity is considered to be 200 mg/kg/day.
A repeated inhalation study for 3 weeks revealed a NOEL of 100 ppm. Nose and eye irritation was
observed at 250 ppm (LOEL).
Two independent gene mutation tests in bacteria [OECD TG 471 & 472] resulted in negative results
except for a positive result in S. typhimurium TA 1537 at 2500 ug without metabolic activation in one
study. A HPRT study on Chinese h amster cultured cells [OECD TG 476] was negative. A chromosomal
aberration test in vitro [TG 473] and a human lymphocyte test were positive with and without metabolic
activation.
However two in vivo studies [micronucleus assay, OECD TG 474] by i.p. or gavage respectively, gave
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
negative results. Based on the weight of evidence, it is concluded that this chemical is not genotoxic in
vivo .
In the above-described OECD combined repeated dose and reproductive/developmental toxicity
screening test [OECD TG 422], there was no sign of reproductive toxicity up to 1000 mg/kg/day for
males. Three females in the 1,000 mg/kg/day group, however, lost all of their pups in the lactation
period. As to the developmental effect, the pups born from the females in the 1000 mg/kg/day group
showed a lower body weight although no external abnormalities were observed. The NOAEL of the
reproductive/developmental toxicity is considered to be 200 mg/kg/day for both parents and offspring.
Environment
Abiotically 2-dimethylaminoethyl methacrylate is hydrolyzed at pH7 and at pH 9 with a half-life of 4.54
days and 3.31 hours, respectively, whereas it is stable at pH 4. This chemical is readily biodegradable
([OECD TG 301E]; BOD: 95.3 % after 28 days), and has low bioaccumulation potential based on its log
Kow of 1.13.
This chemical has been tested in a limited number of aquatic species including algae, daphnids and fish.
The toxicity results (growth inhibition: [OECD TG 201]) for algae (Selenastrum capricornutum) were
41.6 mg/L (72 h-EC50) and 18 mg/L (72 h-NOEC). The acute (immobility: [OECD TG 202]) and chronic
(reproduction: [OECD TG 211]) toxicity results for daphnids are 33 mg/L (48h-EC50), 16.6 mg/L (21d-
LC50), 7.86 mg/L (21d-EC 50), and 4.35 mg/L (21d-NOEC), respectively. The acute LC50 (96 hr: [OECD
TG 203]) and prolonged LC50 (14 d: [OECD TG 204]) for fish (Medaka ; Oryzias latipes) were 19.1 mg/L
and 5.26 mg/L, respectively. Although 2-dimethylaminoethyl methacrylate can be hydrolyzed in these
test conditions to methacrylic acid and dimethylaminoethanol, these results are, however, consistent with
the aquatic toxicity of the metabolites reported in the respective SIARs issued in the past.
Exposure
The production volume of 2-dimethylaminoethyl methacrylate was estimated at approximately 8,000
t/year in Japan and 48,000 t/year world-wide in 2000. 2-Dimethylaminoethyl methacrylate is produced in
a fully-closed system. Most of 2-dimethylaminoethyl methacrylate is industrially converted to the
quaternary ammonium salt and polymerized for flocculant use in water treatment. This chemical is also
used as a component monomer of copolymers in the polymer industry, and the products are used for
paper agents, coatings and others. The workplace exposures during those application processes are
controlled. Fugacity modelng (Mackay level III) predicts that 2-dimethylaminoethyl methacrylate
i
released to water unlikely will migrate into other compartments. 2-Dimethylaminoethyl methacrylate is
readily biodegradable and not persistent in the water phase. When this chemical is released to air, 72 %
stays in air and 28 % is transported into water and soil.
During production and use of this substance occupational exposure is possible by inhalation of vapor.
Consumer exposure is controlled because it is limited to the non-dispersive use.
Migration of residual monomer from the polymer matrix is expected to be low. Nevertheless, the
possibility of exposure cannot be excluded.
NATURE OF FURTHER WORK RECOMMENDED
The chemical is not a candidate for further work considering the low bioaccumulation potential, ready
biodegradability and low aquatic toxicity.
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
FULL SIDS SUMMARY
CAS NO: 2867-47-2 SPECIES PROTOCOL RESULTS
PHYSICAL-CHEMICAL
2.1 Melting Point Unknown - 30 癈
2.2 Boiling Point Unknown 186 癈
0.934 g/cm3 at 20 癈
2.3 Density Unknown
2.4 Vapour Pressure Calculated 1.10 hPa at 25 癈
2.5 Partition Coefficient OECD TG 107 1.13 at 25 癈
(Log Pow)
2.6 A. Water Solubility Unknown 106.1 g/L at 25 癈
B. pH No data available
pKa OECD 112 8.44 at 25 癈
2.12 Oxidation: Reduction No data available
Potential
ENVIRONMENTAL FATE AND
PATHWAY
T 1/2 = 4 hrs
3.1.1 Photodegradation Calculated
3.1.2 Stability in Water OECD TG 111 Stable at pH4 at 50 癈
T 1/2 = 4.54 days at pH7 at 25 癈
T 1/2 = 3.31 hrs at pH9 at 25 癈
3.2 Monitoring Data No study
3.3 Transport and Distribution Calculated (Release 100% to air)
Air Water Soil Sediment
(Level III Fugacity
72.1% 13.6% 14.2% 0.0%
Model)
(Release 100% to water)
Air Water Soil Sediment
0.0% 99.7% 0.0% 0.2%
(Release 100% to soil)
Air Water Soil Sediment
0.1% 5.7% 94.2% 0.0%
3.5 Biodegradation Readily biodegradable
OECD 301E
BOD: 95.3% after 28days
3.7 Bioaccumulation No data available
ECOTOXICOLOGY
4.1 Acute/Prolonged Toxicity Oryzias latipes OECD TG 203 LC50(96hr) = 19.1 mg/L
to Fish
OECD TG 204 LC50(14d) =5.26 mg/L
LC0 (14d) = 1.36 mg/L
4.2 Acute Toxicity to Aquatic Daphnia magna OECD TG 202 EC50(48hr,Imm) = 33 mg/L
Invertebrates (Daphnia )
Selenastrum
4.3 Toxicity to Aquatic Plants OECD TG 201 EC50(72hr,Bms) = 41.6 mg/L
capricornutum
e.g. Algae NOEC(72hr,Bms) =18 mg/L
4.5.2 Chronic Toxicity to Daphnia magna OECD TG 211 EC50(21d,Rep)= 7.86 mg/L
Aquatic Invertebrates
NOEC(21d,Rep)= 4.35 mg/L
(Daphnia )
4.6.1 Toxicity to Soil Dwelling No data available
Organisms
No data available
4.6.2 Toxicity to Terrestrial
Plants
4.6.3 Toxicity to Other Non -
Mammalian Terrestrial
Species (Including Birds)
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
TOXICOLOGY
5.1.1 Acute Oral Toxicity Rat OECD TG 401 LD50 > 2000 mg/kg
5.1.2 Acute Inhalation Mouse Other LC50 (2 h) = 1.8 mg/L (280 ppm)
Toxicity Rat Other LC50 (4 h) = 0.62 mg/L
5.1.3 Acute Dermal Toxicity Rat Other LD50 > 2000 mg/kg
Rabbit LD50 > 3000 mg/kg
5.2.1 Skin Irritation Rabbit Other irritating
5.2.2 Eye Irritation Rabbit Other Corrosive
5.3 Skin Sensitisation Guinea pig OECD TG 406 Not sensitizing
5.4 Repeated Dose Rat OECD TG 422 NOAEL = 200 mg/kg/day (both sexes)
Toxicity
5.5 Genetic Toxicity in vitro
A. Bacterial Test S.typhimurium OECD TG 471 & Positive (for only TA 1537)
(Gene mutation) E. coli 472
S.typhimurium OECD TG 471 Negative
B. Non-Bacterial in vitro CHL cell OECD TG 473 Positive
Test (Chromosomal
aberrations)
Non-Bacterial in vitro Human Other Positive
Test (Chromosomal lympocytes
aberrations)
HPRT Assay V79 Chinese OECD TG 476 Negative
Hamster cell
5.6 Genetic Toxicity in Mouse (p.o) OECD TG 474 Negative
vivo (Micronucleus Mouse (i. p) OECD TG 474 Negative
Test)
5.7 Carcinogenicity No data available
5.8 Toxicity to Rat OECD TG 422 NOAEL Reproductive/Developmental=
Reproduction 200 mg/kg/day.
5.9 Developmental
Toxicity/ No teratogenicity
Teratogenicity
5.11 Experience with No data available
Human Exposure
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
SIDS INITIAL ASSESSMENT REPORT (SIAR)
1. IDENTITY
IUPAC name: 2-Dimethylaminoethyl methacrylate
CAS Number: 2867-47-2
Molecular Formula: C8H15 NO 2
Structural Formula:
CH3
CH2 = C- C- O- CH 2- CH2- N- CH3
O CH 3
Synonyms:
MADAME
DAM
2-(Dimethylamino) ethanolmethacrylate
2-(N, N-Dimethylamino) ethylmethacrylate
2-Dimethylaminoethyl methacrylate
2-Dimethylaminoethyl-2-methyl-propenoate
N, N-Dimethylaminoethyl methacrylate
beta- (N, N-Dimethylaminoethyl) methacrytlate
Dimethylaminoethyl methacrylate
DMAEMA
Ethanol, 2-(dimethylamino)-, methacrylate
Methacrylic acid, 2-(dimethylamino) ethyl ester
2-Propenoic acid, 2-methyl, 2-(dimethylamino)ethyl ester
Purity: > 99.0 %
Physical and chemical properties:
Melting Point -30 癈
Boiling Point 186 癈
0.934 g/cm3 (20 癈)
Density
Vapour Pressure 1.10 hPa (25 癈)
Partition Coefficient 1.13 (25 癈)
(Log Pow)
Water Solubility 106.1 g/L (25 癈)
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. GENERAL INFORMATION ON EXPOSURE
The production volume of MADAME was estimated as approximately 8,000 t/year in Japan and
48,000 t/year world-wide in 2000. Most of MADAME is industrially converted to the quaternary
ammonium salt and polymerized for flocculant use in water treatment. Also, this chemical is used
as a component monomer of copolymers in polymer industry, and t e products are used for paper
h
agents, coatings and others. Thus this chemical is not contained in consumer products in Japan.
From uses and properties of this substance, estimated exposures are considered for the following 3
scenarios.
(1) Occupational exposure scenario
(2) Consumer exposure scenario
(3) Environmental exposure scenario
Migration of residual monomer from the polymer matrix is expected to be low. Nevertheless, the
possibility of exposures cannot be excluded.
2.1 Environmental Fate
The Mackay level III fugacity model was employed to estimate the environmental distribution of
MADAME in air, water, soil and sediment. This was considered the key study and the results are
shown below.
Table 1. Estimated Distribution Under Three Emission Scenarios
Release: Release: Release:
100% to air 100% to water 100% to soil
Air 72.1 % 0.0 % 0.1 %
Water 13.6 % 99.7 % 5.7 %
Soil 14.2 % 0.0 % 94.2 %
Sediment 0.0 % 0.2 % 0.0 %
The results show that if MADAME is released into water, 99.7% stays in water, and it is unlikely to
migrate into other compartments. When MADAME is released to air, 72.1% stays in air and, 13.6
% is transported to water and 14.2 % is transported to soil. However the calculation may include
some uncertainty because of the weak dissociating property of the chemical.
Abiotically this chemical is stable to hydrolysis in water at pH 4 at 50 癈, whereas it is hydrolyzed
at pH 7 and pH 9 at 25 癈 with a half-life of 4.54 days and 3.31 hours, respectively [CERI Japan,
1997]. MADAME is hydrolysed to methacrylic acid (MAA) and 2-dimethylaminoethanol (DMAE).
MADAME is readily biodegradable (OECD 301E: BOD = 95.3% after 28days) [Roehm 1988a].
Both MAA and DMAE, produced by hydrolysis of MADAME, are also readily biodegradable.
(MAA; BOD = 89 ?94% after 14days [CERI Japan, 1993], DMAE; BOD = 60.5 % after 14 days
[CERI Japan, 1976])
MADAME is considered to have a low bioaccumulative potential based on its log Pow (1. 13 at 25
癈) [CERI Japan, 1997].
If this chemical is released to air, indirect photodegradation is predicted to occur. The half-life is
estimated to be 4 hours in the atmosphere.
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2.2 Human Exposure
2.2.1 Occupational Exposure
Occupational exposures at production sites may occur by the inhalation route and dermal route.
The atmospheric concentration was measured at one production site [Japan Industrial Safety and
Health Association (JISHA), 2000]. The monitored data are shown in Table 2.
Table 2: Workplace monitoring data for MADAME
Operation Monitoring Data Frequeny Working Maximum
time EHE
time/day mg/kg/day
hrs/time
1.70 x 10-3
0.19 mg/m3
Drum Filling work 1 0.50
(0.03 ppm)
1.70 x 10-4
0.19 mg/m3
Maintenance work 1 0.050
(0.03 ppm)
8.48 x 10-5
0.19 mg/m3
Sampling 1 0.025
(0.03 ppm)
Total 1.95 x 10-3 mg/kg/day
EHE: Estimated Human Exposure
[Monitoring method]
Air sample was suctioned at the breathing zone of the worker at a suction rate of 0.4 L/min. for 5
min. and adsorbed through a collection can and analyzed by GC.
As shown in Table 2, the monitored exposure concentrations were below 0.19 mg/m3 at the drum
filling work, the maintenance work and the sampling. The highest daily intake (respiratory
EHEinh) for a worker (body weight; 70 kg, respiratory volume; 1.25 m3/hr) assigned to the drum
filling work without protection is calculated as 1.70 x 10-3 mg/kg/day. The duration of dermal
exposure is assumed to be 0.50 hrs/day. EHEder for the worker who implement all daily operation
through hands is calculated as 7.50 x 10-2 mg/kg/day, assuming that the work is classified as non-
dispersive, direct handling, and contact level is incidental. Some production sites may have
batchwise operations and release patterns may differ from the above description.
2.2.1.1 Occupational exposure limit of MADAME
There is no available official recommendation.
2.2.2 Consumer Exposure
MADAME is not considered to be contained in consumer products in Japan, because most of
MADAME is industrially converted to the quaternary ammonium salt and polymerized to form
flocculant to be used in water treatment. This chemical is also used as a component monomer of
copolymers in polymer industry, and the products are used for paper agents, coatings and others.
Migration of residual monomer from the polymer matrix is expected to be low. Nevertheless, the
possibility of exposure cannot be excluded.
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2.2.3 Environmental Exposure
The production volume of MADAME was estimated as 8,000 t /year in Japan, and 48,000 t /year
world-wide in 2000.
According to the monitoring data of Mitsubishi Gas Chemical Co., Inc., 38.5 kg/year of MADAME
with 8.76 x 108 L of effluent is released yearly into seawater. Predicted local environmental
concentration (PEClocal ) is estimated as 4.39 x 10-5 mg/L, employing the following calculation model.
In this case, the dilution factor of 1000 is adopted since most of MADAME released to the
environment is discharged into sea.
Amount of release (3.85 x 10 7 mg/y)
Volume of effluent after treatment (8.76 x 108 L/y) x Dilution factor (1000)
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
3. HUMAN HEALTH HAZARDS
3.1 Effects on Human Health
3.1.1 Toxicokinetics and metabolism
The available data were limited. Two available studies were reviewed and described below.
Small quantities of methacrylates may readily be metabolized by saponification into the alcohol and
methacrylic acid. The latter may form an acetyl-CoA derivative, which then enters the normal lipid
metabolism [Clayton/Patty, 1993-1994]. The substance was rapidly hydrolysed to methacrylic acid
(MAA) and N,N-dimethylaminoethanol (DMAE) when incubated with simulated saliva or
simulated intestinal fluid in vitro . 90 % degradation was observed in simulated saliva after 4 hrs at
37 癈, 86 % degradation after incubation with simulated intestinal fluid for 4 hrs at 37 癈.
Degradation was below 8% after incubation with simulated gastric fluid for 4 hours at 37 癈
[Atochem, 1994]. However, no in vivo study is available.
3.1.2 Acute toxicity
There were various studies on the acute toxicity by different administration routes. Eleven reports
on the acute toxicity via oral, dermal, inhalation or other routes to rats, mice or rabbits were
reviewed and summarized in the table shown below. As for oral toxicity, the study by MHW
[MHW Japan,1998] was considered to be the most reliable and identified as the key study because
it was well conducted according to OECD TG 401 in compliance with GLP. The details of this
study were as follows.
SD rats (5/sex/dose) were administered doses of 0 (vehicle), 500, 1000, 2000 mg/kg/day by gavage.
Although raised patches and papillomatous hyperplasia in the forestomach were observed, no death
occurred in the 2000 mg/kg/day dose. The oral acute toxicity LD50 is considered to be greater than
2000 mg/kg bw. As for dermal toxicity, the study on rats by Atochem [Atochem, 1992a] was
conducted in accordance with OECD TG 402 in compliance with GLP and identified as the key
study. At 2000 mg/kg dose, no mortality was observed although the symptom of hypokinesia,
sedation dyspnea and skin irritation were observed. The dermal acute lethal dose is considered to
be greater than 2000 mg/kg bw. Regarding toxicity by inhalation, although inhalation is a key route
of exposure for this substance, only two values were reported [Izmerov, 1982] and these were not
reliable because no detailed data were available. As to the acute toxicity by intraperioneal
administration (i.p.), various values were reported in three tests on rats or mice. The severest value
was 25 mg/kg bw for mice [NTIS, 1986].
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
Table 3. Acute toxicity of MADAME in experimental animals.
Route Animals Values Type References Reliability
Oral Rat > 2,000 mg/kg bw LD50 MHW Japan, 1998 Reliable
Oral Rat = 1,751 mg/kg bw LD50 Izmerov, 1982 Not reliable
Oral Rat = 2,659 mg/kg bw LD50 Roehm, 1978 Reliable
Oral Rat = 1,550 mg/kg bw LD50 Kirk-Othmer, 1984 Not reliable
Dermal Rat > 2,000 mg/kg bw LD50 Atochem, 1992a Reliable
Dermal Rabbit > 3,000 mg/kg bw LD50 Kirk-Othmer, 1984 Not reliable
Inhalation/ Rat = 0.62 mg/L LC50 Izmerov, 1982 Not reliable
4hrs
Inhalation/ Mouse = 1.8 mg/L (280 ppm) LC50 Izmerov, 1982 Not reliable
2hrs
i.p. Rat = 97 mg/kg bw LD50 Kirk-Othmer, 1984 Not reliable
i.p. Rat = 310 mg/kg bw LD50 Paulet, G., 1975 Not reliable
i.p. Mouse = 25 mg/kg bw LD50 NTIS, 1986 Not reliable
Human data
There is no available information.
Conclusions:
(Oral toxicity) At the highest dose of 2000 mg/kg, no mortality occurred. The acute oral LD50 of
this chemical is considered greater than 2000 mg/kg bw. The acute toxicity of this substance can
thereby be considered to be low.
(Dermal toxicity) Although hypokinesia, sedation, dyspnea and skin irritation were observed, no
mortality occurred at 2000 mg/kg in rats. The acute dermal toxicity for rats is considered to be
greater than 2000 mg/kg bw.
3.1.3 Repeat dose toxicity
Four studies of varied validity have been located. Two of them were oral administration studies and
the other two were dermal and inhalation toxicity studies. One of the oral studies by MHW was
identified as the key study because it was conducted according to OECD TG 422 in compliance
with GLP [MHW Japan, 1998]. The other oral study was not reliable due to lack of data and was
omitted from this assessment. The dermal study [Manabe, 1990] seems not reliable because no
detailed data were available. The inhalation study [Gage, 1970] seems to be reliable and was
identified as a key study.
(Oral Gavage) According to the OECD test guidelines for combined repeat dose and
reproductive/developmental toxicity screening [OECD TG 422], SD (Crj: CD) rats was
administrated with gavage doses of 0 (vehicle ; corn oil), 40, 200, and 1000 mg/kg/day. The dosing
period for males was 43 days, and for females were 41 to 52 days, from 14 days before mating to
the day 3 of lactation. The results are summarized below.
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
Table 4. The result of the repeated oral dose test
Dose mg/kg/day Symptom
1000 Males : No death occurred.
The following adverse effects were observed.
*Late onset of twitching, chronic convulsion and the suppression
of body weight gain.
*By histopathological examination:
Degeneration of nerve fibers in the brain and spinal cord, and
hyperplasia of the mucosa, edema and inflammatory cell
infiltration in the forestomach. Increase in the weight of the
kidneys and livers without histopathological changes.
*By blood examination:
Slight increase in BUN and slight anemic changes such as
decreases in erythrocyte counts, hemoglobin concentration and
hematocrit value, associated with a significant increase in
reticulocyte ratio.
Females: 3 animals out of 12 died.
The following adverse effects were observed in the surviving
animals.
* Late onset of twitching, chronic convulsion, suppression of body
weight gain and decrease of food consumption during the
lactation period.
*By histopathological examination:
Degeneration of nerve fibers in the brain and spinal cord, and
hyperplasia of the mucosa in the gastric tract, edema and
inflammatory cell infiltration in the forestomach and atrophy of
the thymus. Increase in the weight of the kidneys and the
adrenals without histopathological changes.
200 Males : No adverse effects were observed except for slight anemic
changes such as decreases in hemoglobin concentration,
hematocrit value and increase in reticulocyte ratio.
Females: No effects were observed.
40 No effects for both sexes were observed.
Although slight anemic changes were observed in males of the 200 mg/kg/day group, the severity
was considered toxicologically insignificant [MHW Japan, 1998]. The NOAEL for the repeat dose
toxicity is considered to be 200 mg/kg/day for both sexes.
(Inhalation) Short-term vapor inhalation toxicity was studied in rats with a constant flow pump for 3
wks, 5 d/w, 6 h/d. At 250 ppm (1606 mg/m3), nose and eye irritation, labored breathing were
observed. The body weight gain was slow. There were no changes in the hematological
parameters. No pathological (macroscopical and microscopical) effect on organs was observed. At
100 ppm (643 mg/m3), no toxic effects were observed [Gage, 1970]. The NOAEL for repeated
inhalation toxicity is considered to be 100 ppm (643 mg/m3).
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Human data
There is no available information.
Conclusions:
(Oral) At 1000 mg/kg/day, three of twelve females died. For both sexes, the adverse effects shown
in the above table were observed. At 200 mg/kg/day, aalthough slight anemic changes such as
decreases in hemoglobin concentration, hematocrit value and increase in reticulocyte ratio were
observed in males, the severity was considered toxicologically insignificant. The NOAEL for
repeat dose oral toxicity is considered to be 200 mg/kg/day for both sexes.
(Inhalation) At 100 ppm (643 mg/m3), no toxic effects were observed. The NOAEL in the 3wks
repeated dose inhalation toxicity study is considered to be 100 ppm (643 mg/m3).
3.1.4 Genetic Toxicity
Genetic Toxicity
Seven reports were reviewed and summarized in the table shown below. These were two bacterial
in vitro test reports, three non-bacterial in vitro test reports and two genetoxic in vivo test reports.
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OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
Table 5. Summary of genetoxicity studies
Type of test Test system Dose Result Reference
Bacterial in vitro test
Reverse S. typhimurium Up to 5000 With MA*: MHW Japan,
mutation (strains TA100, ug/plate Negative for all 1998
TA1535, TA98, strains at all doses.
TG 471 & 472 TA1537)
E. coli WP2 uvr A
Up to 5000 Without MA:
ug/plate Positive only at
2500 and 3000
Toxicity was ug/plate for
observed at 3500 TA1537.
ug/plate and more. Negative for all
other strains at all
doses.
S. typhimurium Up to 5000 Negative Atochem, 1991a
(strains TA1535, ug/plate (+ & - MA)
TA1537, TA1538,
TA98 and TA100)
Non Bacterial in vitro test
Chromosomal CHL/IU cells Up to 1.6 Positive MHW Japan,
aberration test mg/mL (+ & - MA) 1998
TG 473 Human lympocytes Up to 1.57 Positive Atochem, 1991b
mg/mL (+ & - MA)
HPRT assay V79 Chinese hamster Up to 2.0 Negative Atochem, 1992b
TG 476 cells mg/mL with (+ & - MA)
S9 Mix.
Genetic in vivo test
Micronucleus Mice (i. p) 200 mg/kg bw Negative Atochem, 1993
Test Two
TG 474 administrations,
24 hrs interval.
Mice (p. o) Up to 1000 Negative Rohem, 1989
mg/kg bw
* MA: Metabolic activation
Bacterial tests
Two studies were reviewed. These two studies were conducted according to OECD TG 471 & TG
472 in compliance with GLP and were identified as the key studies [MHW Japan, 1998] [Atochem,
1991a].
1) MHW, Japan (1998): Screening Mutagenicity Testing of Chemicals
The test was conducted two times for all cells with and without S9 and the results were positive
without S9 at 2500 ug/plate and higher for TA 1537 and TA 98. Then the confirmation test was
conducted for S. typhimurium TA 1537 and TA 98 without S9. Toxic effects were observed at 3500
ug/plate and higher concentrations to TA 98 and TA 1537 without S9 mix.
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The result of the confirmation test was positive only for TA 1537 at 2500 and 3000 ug/plate. The
number of the induced revertant colonies per mg was calculated as 3.6.
2) Atochem (1991a):
Atochem reported that MADAME was negative in any of S. typhimurium TA 1535, TA 1537, TA
1538, TA 98 and TA 100 at doses of 10, 100, 1000, 2500, and 5000 ug/plate with and without S9.
Non-bacterial in vitro tests
Three studies were reviewed. Two studies were chromosomal aberration tests by OECD TG 473 on
cultured Chinese hamster lung cells [MHW Japan, 1998] and on human lymphocytes [Atochem,
1991b].
Another study was conducted according to OECD TG 476: HPRT/V 79 [Atochem, 1992b]. These
three tests were conducted in compliance with GLP and were identified as key studies. The three
studies are summarized below.
1) MHW, Japan (1998): Chromosomal aberrations assay on cultured Chinese hamster lung cells
After 24 hrs and 48 hrs continuous treatment without S9, structural chromosomal aberrations
(including gap) were induced at 625 ug/mL with 88.5% and 76.5% respectively. The number of
cells with aberrations excluding gaps were 86.5% and 74.0% respectively. Cytotoxicity was
observed at 625 ug/mL and 313 ug/mL. By the 6 hrs short-term treatment without S9,
concentration-dependent structural chromosomal aberrations (including gap) were induced at 200
ug/mL, 400 ug/mL and 600 ug/mL with 6.5 %, 49.5 % and 87.5 % respectively. The number of
cells with aberrations excluding gaps were 6.5%, 46.0% and 86.0% respectively. By the 6 hrs
short-term treatment with S9, concentration-dependent structural chromosomal aberrations
(including gaps) were induced at 800 ug/mL, 1400 ug/mL and 1600 ug/mL with 13.5 %, 99.5 %
and 100 % respectively.
The number of cells with aberrations excluding gaps were 13.0%, 99.5% and 100.0% respectively.
Polyploidy was not induced under any of these conditions. At more than 800 ug/mL of the 6 hrs
short-term treatment without S9 mix and at more than 1600 ug/mL with S9 mix, cytotoxicity was
observed. As a result, MADAME is considered to induce chromosomal aberrations with and
without metabolic activation. However, the aberrations were mainly chromatid breaks and
chromatid exchanges.
2) Atochem (1992b): Chromosomal aberrations assay on human lymphocytes
The dose levels were up to 1572 ug/mL (maximum solubility). The cells sampled at 20 hours after
the start of the treatment were analysed for chromosomal aberrations. At the higher two
concentrations, namely 1179 ug/mL without S9 and 1572 ug/mL with S9, this chemical induced
aberrations which were significantly different from those observed in the concurrent solvent
controls. No exchange-type aberrations were observed, but only deletion-type aberrations were
seen. The number of cells with aberrations excluding gaps (average of two tests) at 1179 ug/mL
without S9 and 1572 ug/mL with S9 were 11.0% and 7.5% respectively. No marked mitomic
inhibition was evident in any of the doses analysed in this study. The mitomic index at 1179 ug/mL
without S9 and 1572 ug/mL with S9 was 2.3 % and 6.2 % respectively. It is concluded that
MADAME may induce chromosomal aberrations in the human peripheral blood lymphocytes with
and without metabolic activation.
3) Atochem (1992b): HPRT/V79 Chinese hamster cell test
The test was conducted at concentrations from 31.25 to 2000 ug/mL. With and without metabolic
activation, MADAME showed some cytotoxic effects at concentrations higher than 250 ug/mL, but
no increase in the mutation frequencies were observed at any concentrations tested. Under these
experimental conditions, MADAME was not genotoxic.
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Genetoxic in vivo tests
Two micronucleus assays were reviewed. These two studies were conducted according to OECD
TG 474 in compliance with GLP and were identified as key studies [Atochem, 1993], [Roehm,
1989]. The summary of the studies is shown below.
1) Atochem (1993): on the clastogenic potential of MADAME in OF1 mice
The animals (5 males and 5 females per group) received two administrations separated by 24 hrs,
of 200 mg/kg by the intraperitoneal route. Cyclophosphamide at the dose level of 25 mg/kg (two
times i.p. injection) served as the positive control. The test animals were killed at 24 or 48 hrs
after the 2nd administration and the bone marrow smears were examined for the presence of
micronuclei in 2000 polychromatic erythrocytes per mouse and for the PCE/NCE ratio. The
number of the micronucleated polychromatic cells in the dosed animals was not significantly
different from that of the animals in the control groups.
MADAME did not induce cytogenetic damage to the bone marrow cells of mice in this test.
The summary of the test results is shown below.
Time of sacrifice: 24 hrs after the 2nd administration
Group doses MPE/PE PE/NE ratio
--------- (mg/kg) Mean (SD) Mean (SD)
vehicle ----- 2.0 (0.8) 0.7 (0.2)
Test substance 200 1.9 (1.1) 0.6 (0.2)
CPA 25 18.2 (3.8)# 0.4# (0.1)
Time of sacrifice: 48 hrs after the 2nd administration
Group doses MPE/PE PE/NE ratio
(mg/kg) Mean (SD) Mean (SD)
vehicle 1.9 (0.8) 0.9 (0.4)
Test substance 200 1.7 (1.0) 1.2 (0.6)
10 animals(5 males, 5 females) per group
# : P < 0.001
Vehicle: physiological solution
CPA : cyclophosphamide
PE : polychromatic erythrocytes
NE : normochromatic erythrocytes
MPE/PE: micronucleated polychromatic erythrocytes/1000 Polychromatic erythrocytes.
(SD) : standard deviation.
2) Roehm (1989): on the clastogenic potential of MADAME in NMRI mice
The maximum tolerated dose of 1000 mg/kg bw, dissolved in water, was administered by oral
gavage to 3 groups of 10 NMRI mice (5 males and 5 females). As negative control, distilled
water was served. As positive control, cyclophosphamide in physiological serum (NaCl) was
dosed at 40 mg/kg. The test mice were killed at 24, 48 or 72 hrs after the administration. The
bone marrow smears were examined for the presence of micronuclei in 1000 polychromatic
erythrocytes per mouse and for the PCE/NCE ratio. No significant increase of micronuclei was
observed compared to the negative control group. No micronuclei induction due to MADAME
was observed.
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The summary of the test results is shown below.
Sampling time: 24 hrs
Group Dose PCEs with Micronuclei in PCE/NCE
mg/kg bw Micronuclei 1000 PCE (mean)
(%) (Range)
Solvent 0 0.06 0? 1000 / 554
Test article 1000 0.03 0? 1000 / 653
CPA 40 0.75 1 ?13 1000 / 742
Sampling time: 48 hrs
Group Dose PCEs with Micronuclei in PCE/NCE
mg/kg bw Micronuclei 1000 PCE (mean)
(%) (Range)
Solvent 0 0.04 0? 1000 / 680
Test article 1000 0.04 0? 1000 / 744
Solvent: distilled water
CPA : cyclophosphamide
PCE : polychromatic erythrocytes
NCE : normochromatic erythrocytes
Conclusions:
Two independent gene mutation tests in bacteria resulted in negative results except for one positive
result in S. typhimurium TA1537 at 2500 ug/plate without metabolic activation in one study. A
HPRT study with Chinese hamster cultured cells was negative. Chromosomal aberration tests in
vitro and a human lymphocyte test were positive for clastogenicity with and without metabolic
activation. Two in vivo micronucleus assays by i.p. or gavage respectively, however, are negative
for clastogenicity. Based on the weight of evidence, it is concluded that this chemical is not
genotoxic in vivo.
3.1.5 Carcinogenicity
No data are available.
3.1.6 Reproduction/developmental toxicity
There was only one study available. The combined repeat dose and reproductive toxicity study by
the oral route [MHW Japan, 1998] was identified as the key study because it was conducted
according to OECD TG 422 in compliance with GLP.
Reproductive and developmental study: SD (Crj: CD) rats received gavage doses of 0 (vehicle;
Corn oil), 40, 200 and 1,000 mg/kg/day, for males for 14 days before mating and for females from
14 days before mating to day 3 of lactation. The animals were sacrificed on day 4 of lactation for
females. There were no effects on the reproductive parameters such as the mating index, the
fertility index, the number of corpora lutea or implantations, the implantation index, the delivery
index, the gestation index and the gestation length or the parturition. Three females in the 1000
mg/kg/day group, however, lost all of their pups during the lactation period. Also it should be noted
that females in the 1000 mg/kg/day group showed many adverse effects in the repeated oral dose
test such as death of 3 animals out of 12, late onset of twitching, chronic convulsion, the
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suppression of body weight gain, degeneration of nerve fibers in the brain and spinal cord,
hyperplasia of the mucosa in the gastric tract, the edema and inflammatory cell infiltration in the
forestomach, atrophy of the thymus, increase in the weight of the kidneys and the adrenals without
histopathological changes. The pups from the females in the 1000 mg/kg showed lower body
weights and were lower in the viability index due to maternal nursery activity. It is reported that by
external inspection, no abnormalities were found. However, a lower body weight gain and a lower
viability index were observed in the pups from the females of the 1000 mg/kg/day group. The
NOAEL for the reproductive/developmental toxicity is considered to be 200 mg/kg/day.
Human Data
There is no available information on humans.
Conclusions:
The NOAEL of this chemical for the reproductive/developmental toxicity is considered to be 200
mg/kg/day.
3.1.7 Other human health related information
1) Irritation (skin and eye) and sensitizing potential
The summaries of these studies are shown in the table below.
Table 6:The summary of other human health related information
Species Method Result Reference
Irritation(skin)
Rabbit Occlusive patch Corrosive. Atochem, 1980
Federal Register Primary irritation score: 8.0
(USA)-29 FR13009,
1964
Rabbit Draize test Highly irritating Roehm, 1977
Draise index: 5.9 of 8
(reevaluated according to
OECD 404)
Guinea pig No data Irritation occurs even when Roehm, 1977
using silicon or 5% Zn cream.
Irritation (eye)
Rabbit Federal Register Corrosive: Atochem, 1980
(USA)-9
FR13009, 1964
Sensitization
Guinea pig OECD TG 406 Negative: Atochem, 1991c
Split adjuvant No cutaneous reactions
(Skin irritation) There are three reports available. Among them, the study by Atochem was
identified as the key study because it was conducted according to the recommendations of the
Federal Hazardous Substances Labelling Act Regulations, Section 191.11, published in the Federal
Register (USA)-29 FR13009, 1964 [Atochem, 1980]. MADAME was administrated to the intact
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and abraded skin of New-Zealand albino rabbits at the dose level of 0.5 mL per animal under the
occlusive patch for 24 hours.
The cutaneous reactions were observed just after the removal of the patch and after 72 hours.
Severe erythema, oedema and necrosis were observed after the test and these symptoms persisted to
the inspection after 72 hours of the test. A primary irritation score of 8.0 was obtained. Under
these test conditions, MADAME was considered to be corrosive to the skin.
(Eye irritation) The only study available was considered to be reliable because it was conducted in
accordance with the recommendations of the Federal Hazardous Substances Labelling Act
[Atochem, 1980]. Severe cornea, iris and conjunctive lesions were displayed in all animals within 2
hours after the instillation of 0.1mL MADAME. MADAME was considered to be corrosive to
eyes.
(Sensitization) There was only one study available. The sensitizing potential of MADAME was
evaluated by a modified Magnusson and Kligman method according to the OECD guideline No.
406 with the principles of Good Laboratory Practice and was identified as a key study [Atochem,
1991c].
The general behaviour and the body weight gain of the animals were not influenced by the
treatment. After the challenge test, a very slight erythema (score 1) was observed on the right flank
of 16 out of 20 treated animals. As the cutaneous reactions were very slight and the reactions
observed at the 24 hours scoring period were reversible at the 48 hours scoring period, the
cutaneous reactions were attributed to orthoergique reaction. No cutaneous reaction likely to be
caused by a sensitization potential of MADAME were observed.
2) Other toxic information
Other available toxic information are summarized in the table shown below.
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Table 7. The summary of other toxic information
Species Method Result (Symptoms) Reference
Pharmacology
Dogs (anesthetized) Intravenous Elicited a hypertensive effect. Mir, 1974
administration Produced a 28-67 % increase in
0.0026 to 0.028 mL blood pressure with small doses.
10-3, 10-4, 10-5 (v/v)
Rabbit (isolated and Reduction of the heart rate, the force Mir, 1973
perfused) concentration. of contraction and the coronary flow
Examined the activity. rate.
Cardiac standstill at a concentration
of 10-4 (v/v).
4 x10-5, 2 x 10-5 and
Guinea pig The ileum was stimulated by this Mir, 1973
10-5 v/v concentration.
(isolated) chemical, the effect was not
Examined the ileum antaginised by atropine.
activity.
Others
Cytotoxicity Cell growth inhibition ID50 > 100 umol/L (endpoints Hanks, 1975
in Balb/c 3T3 observed: inhibition of DNA
Fibroblasts synthesis, protein synthesis, total
ptotein content, irreversible inhibition
of cell metabolism)
Enzyme inhibition Choline esterase The substance did not inhibit Rowell, 1976
in vitro inhibition cholinesterase activity of the isolated
enzyme or in rat brain preparations in
vitro.
In general, the mode of pharmacological action is cholinergic. However, the mode of action in rat
brain and nervous cells found in the repeated dose study has not been elucidated.
3) Information on structurally related chemicals:
Methyl methacrylate (MMA) (CAS N r. 80-62-6)
MADAME belongs to esters of methacrylic acid. However, MADAME is unique in the
hydrophilic and alkaline nature and relatively low volatility (vapour pressure), that makes a
substantial difference from other analogues in the toxicological properties. The most representative
chemical among the analogues is MMA. According to the SIDS of MMA, inhaled MMA is
metabolised by local tissue esterase. Inhalation is the most relevant route to evaluate the toxicity
and the main effect is a degeneration of the olfactory region of the nose in rat or mouse studies.
Other systemic toxicity effects are degenerative and necrotic lesions in liver, kidney, brain and
atrophic changes in spleen and bone marrow, part of which may have been modulated by
physiological changes in experimental animals. These effects were not seen in chronic studies up
to 1000 ppm. Oral administration to rats resulted in a NOAEL of 200 mg/kg/day.
MMA has in vitro the potential of mutagenic effects, especially clastogenicity. However, this
potential is limited to high doses with strong toxic effects. Furthermore, the negative in vivo
micronucleus test and negative dominant lethal assay indicate that this potential is not expressed in
vivo. There is no relevant concern regarding carcinogenicity of MMA in humans and animals.
Epidemiology data on increased tumour rates in exposed cohorts are of limited reliability and
cannot be related to MMA as the solely causal agent. MMA did not reveal an effect on male
fertility when animals had been exposed to up to 9000 ppm.
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From the available developmental toxicity investigations, including an inhalation study according
to OECD guideline 414, no teratogenicity, embryotoxicity or fetotoxicity has been observed at
exposure levels up to and including 2028 ppm (8425 mg/m3).
Human data
No data are available.
3.2 Initial Assessment for Human Health
Human Health Hazards
This chemical is supposedly metabolized to methacrylic acid (MAA) and N,N-
dimethylaminoethanol (DMAE). Then the MAA may form an acetyl-CoA derivative,which then
enters the normal lipid metabolism. The oral LD50 in rats is greater than 2000 mg/kg. This
chemical is considered to be severely irritating or corrosive to skin and eye. This chemical does not
have a sensitizing potential.
The OECD combined repeat dose and reproductive/developmental toxicity screening test [OECD
TG 422] was conducted in rats at doses of 0, 40, 200 and 1000 mg/kg/day administered by gavage.
For both sexes, a clear systemic toxicity was demonstrated only at 1000 mg/kg/day. Late onset of
twitching, chronic convulsion and the suppression of body weight gain were observed. Three
females out of 12 died. Histopathological examination revealed degeneration of nerve fibers in the
brain and spinal cord, and hyperplasia of the mucosa, edema and inflammatory cell infiltration in
the forestomach in both sexes. Increases in organ weights without histopathological changes were
observed in the kidneys of both sexes, the livers of males, and the adrenals of females in this group.
For the males in this group, BUN was slightly increased and anemic changes such as decreases in
erythrocyte counts, hemoglobin concentration and hematocrit value, associated with a significant
increase in reticulocyte ratio were observed. In males from the 200 mg/kg/day group, only slight
anemic changes such as those observed at 1000 mg/kg/day were seen, but the severity was
considered toxicologically insignificant. The NOAEL for the repeat dose toxicity is considered to
be 200 mg/kg/day.
A repeated inhalation study for 3 weeks revealed a NOEL of 100 ppm. Nose and eye irritation was
observed at 250 ppm (LOEL).
Two independent gene mutation tests in bacteria [OECD TG 471 & 472] resulted in negative results
except for a positive result in S. typhimurium TA 1537 at 2500 ug without metabolic activation
system in one study. A HPRT study on Chinese hamster cultured cell [OECD TG 476] was
negative. A chromosomal aberration test in vitro [TG 473] and a human lymphocyte test were
positive with and without metabolic activation. However two in vivo studies [micronucleus assay,
OECD TG 474] by i.p. or gavage respectively, gave negative results. Based on the weight of
evidence, it is concluded that this chemical is not genotoxic in vivo.
In the above-described OECD combined repeat dose and reproductive/developmental toxicity
screening test [OECD TG 422], there w as no sign of reproductive toxicity up to 1000 mg/kg/day for
males. Three females in 1,000 mg/kg/day, however, lost all of their pups in lactation period. As to
the developmental effect, the pups born from the females in 1000 mg/kg/day group showed a lower
body weight although no external abnormalities were observed. The NOAEL of the
reproductive/developmental toxicity is considered to be 200 mg/kg/day for both parents and
offspring.
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4. EFFECTS ON THE ENVIRONMENT
4.1 Aquatic Effects
MADAME has been tested in a limited number of aquatic species. Results are summarised in Table
8. All the data shown here were derived from experiments conducted under GLP, and the chemical
concentrations in the testing media were analyzed during the course of the experiments. The lowest
chronic result was 4.35 mg/L (Daphnia magna 21d-NOEC, reproduction).
Table 8: Summary of effects of MADAME on aquatic organisms
Organism Test duration Result (mg/L) Reference
algae
Green alga 72 h (op) EC 50 (bms) = 41.6 (nc) MOE, Japan 1997
(Selenastrum
NOEC (bms) = 18 (nc)
capricornutum)
Invertebrates
Water flea (Daphnia
48 h (op,ss) EC 50 (imm) = 33 (mc) MOE, Japan 1997
magna)
------------------ -------------------------------- --------------------------
LC 50 = 16.6 (mc) MOE, Japan 1997
21 d (op,ss)
EC 50 (rep) = 7.86 (mc)
NOEC (rep) = 4.35 (mc)
Fish
Medaka (Oryzias
96 h (op,ss) LC 50 = 19.1 (mc) MOE, Japan 1997
latipes)
14 d (ss) LC 50 = 5.26 (mc)
op: open system
f: flow through ss: semi-static
nc: nominal concentration
mc: calculated based on measured concentrations, because some data of measured concentrations
were < 80 % of nominal concentrations.
bms: biomass imm: immobilization rep: reproduction
The results of the algal inhibition test with Selenastrum capricornutum are based on nominal
concentrations of MADAME. Analytical measurements showed that concentrations of MADAME
decreased during the test from 80.9-88.2% of nominal concentrations at the start of the test to 0.39-
2.18 % of nominal concentrations at the end of the test. The pH in the test system was 9.03-9.25 at
the start of the test and 7.9-9.13 at the end of the test. As the test substance hydrolyses rapidly (half-
life 4.54 days at pH 7 and 3.31 hours at pH 9), it can be assumed that the observed effects are
partially due to the hydrolysis products methacrylic acid and N,N-dimethylaminoethanol.
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4.2 Toxicity to Terre strial Organisms
One study was found for terrestrial toxicity in birds on MADAME. The value of LD50 (18hr) was
described as 98 mg/kg for Agelais phoenicus [Schafer 1983].
4.3 Other
A toxicity test in bacteria was reported on MADAME. The value of EC10 (18hr) in Pseudomonas
putida was 42.7 mg/L [Roehm (1988b)].
4.4 Initial Assessment for the Environment
The results of a generic fugacity model (Mackay level III) show that if MADAME is released into
water, 99.7 % stays in water and 0.2 % is transported to sediment. When MADAME is released to
air, 72.1 % stays in air, 13.6 % is transported to water, and 14.2 % is transported to soil. This
chemicalis readily biodegraded [Roehm, 1988] and is considered to have a low bioaccumulative
potential based on its log Pow (1.13 at 25 癈) [CERI, Japan: 1997].
Information on the aquatic toxicity of MADAME is limited. Results for algae, fish and/or aquatic
invertebrates are summarized below.
The toxicity results (growth inhibition: [OECD TG 201]) for algae (Selen astrum capricornutum)
were 41.6 mg/L (72 h-EC50) and 18 mg/L (72 h-NOEC). The acute (immobility: [OECD TG 202])
and chronic (reproduction: [OECD TG 211]) toxicity results for daphnids are 33 mg/L (48h-EC50),
16.6 mg/L (21d-LC50), 7.86 mg/L (21d-EC 50), and 4.35 mg/L (21d-NOEC), respectively. The acute
LC50 (96 hr: [OECD TG 203]) and prolonged LC50 (14 d: [OECD TG 204]) for fish (Medaka;
Oryzias latipes) were 19.1 mg/L and 5.26 mg/L, respectively.
Due to the half-life of 2-Dimethylaminoethyl methacrylate in water at the test conditions the aquatic
toxicity of the hydrolysis products have to be considered.
Toxicity data for aquatic organisms:
Methylacrylic acid CAS No.: 79-41-4 (EU Risk Assessment Report)
? Fish (Oncorhynchus mykiss): 96 h LC50 = 85 mg/l
? Daphnia magna : 48 h EC50 >130 mg/l
21 d NOEC 53 mg/l (parent mortality, reproduction rate)
? Algae (Selenastrum capricornutum): 72 h EbC50 = 20 mg/l
72 h NOEC = 8.2 mg/l
2-Dimethylaminoethanol CAS No.: 108-01-0 (SIAR)
? Fish (Fathead minnow): 96 h LC50 = 81 mg/l
? Daphnia magna : 48 h EC50 = 98.77 mg/l
? Algae (Scenedesmus): 72 h EC50 = 35 mg/l
All toxicity data from both the mother substance and the hydrolysis products are in the same order
of magnitude.
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5. Conclusions and Recommendations
5.1 Conclusions
Exposure
The production volume of MADAME was reported as approximately 8,000 t/year in Japan and
48,000 t/year world-wide in 2000. MADAME is produced in a fully-closed system. Most of
MADAME is industrially converted to the quaternary ammonium salt and polymerized for
flocculant use in the water treatment. Also, this chemical is used as a component monomer of
copolymers in polymer industry, and the products are used for paper agents, coatings and others.
The workplace exposures during those application processes are controlled.
Fugacity modeling (Mackay level III) predicts that MADAME released to water unlikely will
migrate into other compartments. MADAME is readily biodegradable and not persistent in the
water phase. When this chemical is released to air, 72 % stays in air and 28 % is transported into
water and soil.
From production, uses and properties of this substance, estimated exposures are considered in 3
scenarios;
(1) Occupational exposure scenario: inhalation of vapor without breathing protection in the factory;
Vapor level was 0.19 mg/m3 as measured at the drum filling workplace;
EHEinh = 0.0017 mg/kg/day and EHEder = 0.075 mg/kg/day, using estimation methods.
(2) Consumer exposure scenario: Exposure is controlled because of the non dispersive use.
Migration of residual monomer from the polymer matrix is expected to be low. Nevertheless, the
possibility of exposures cannot be excluded.
(3) Environmental exposure scenario: emission to aquatic compartment from waste water;
PEClocal water = 0.0000439 mg/L using estimation methods.
Hazards to the Environment
MADAME is readily biodegradable (OECD 301E; BOD: 95.3 % after 28 days), and has a low
bioaccumulation potential based on its log Pow (1.13). Abiotically this chemical is stable at pH 4,
whereas it is hydrolyzed at pH 7 and at pH 9 with half-lifes of 4.54 days and 3.31 hours, respectively.
This chemical has been tested in a limited number of aquatic species including algae, daphnid and
fish. The toxicity results (growth inhibition: [OECD TG 201]) for algae (Selenastrum
capricornutum) were 41.6 mg/L (72 h-EC50) and 18 mg/L (72 h-NOEC). The acute (immobility:
[OECD TG 202]) and chronic (reproduction: [OECD TG 211]) toxicity results for daphnids are 33
mg/L (48h-EC50), 16.6 mg/L (21d-LC50), 7.86 mg/L (21d-EC 50), and 4.35 mg/L (21d-NOEC),
respectively. The acute LC50 (96 hr: [OECD TG 203]) and prolonged LC50 (14 d: [OECD TG 204])
for fish (Medaka; Oryzias latipes) were 19.1 mg/L and 5.26 mg/L, respectively.
Human health
The acute toxic ity of this chemical is low because LD50 values are greater than 2000 mg/kg by the
oral route.
This chemical is severely irritating or corrosive to skin and eye. Although only one study was
available, this chemical had no sensitizing effect [OECD TG 406].
The NOAEL for the repeat dose toxicity by the combined repeat dose and reproduction /
developmental toxicity screening test [OECD TG 422], is considered to be 200 mg/kg/day for both
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sexes. A repeated inhalation study for 3 weeks revealed a NOEL of 100 ppm. Nose and eye
irritation was observed at 250 ppm (LOEL).
In the above-described OECD combined repeat dose and reproduction / developmental toxicity
screening test [MHW Japan, 1998/OECD TG 422], there was no sign of reproductive or
developmental toxicity up to 1000 mg/kg/day for males. Three females in the 1000 mg/kg/day
group, however, lost all of their pups in the lactation period. As to the developmental effect, the
pups born from the females in the 1000 mg/kg/day group showed a lower body weight gain
although no external abnormalities were observed. The NOAEL for reproductive/developmental
toxicity is considered to be 200 mg/kg/day for both parents and offspring.
Two independent gene mutation tests in bacteria [OECD TG 471 & 472] resulted in negative results
except for a positive result in S. typhimurium TA 1537 at 2500 ug without metabolic activation
system in one study.
A HPRT study on Chinese hamster cultured cell [OECD TG 476] was negative. A chromosomal
aberration test in vitro [MHW Japan, 1998/TG 473] and a human lymphocyte test were positive
with and without metabolic activation. However two in vivo studies [micronucleus assay, OECD
TG 474] by i.p. or gavage respectively, negative gave negative results. Based on the weight of
evidence, it is concluded that this chemical is not genotoxic in vivo.
5.2 Recommendations
The chemical is currently of low priority for further work.
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6. REFERENCES
Atochem (1980), Skin and Ocular Irritation test, Consultox Lab: CL80 65:2030
Atochem (1991a), Ames test, CIT 7331 MMO
Atochem (1991b), Clastogenicity test in cultured Human Lymphocytes, Hazleton 11/HLC
Atochem (1991c), Skin Sensitization test, CIT 7305 TSG
Atochem (1992a), Acute Dermal Toxicity test in Rats, CIT 8537 TAR
Atochem (1992b), HPRT Gene Mutation Assay in CHO Cells, CIT 8515 MVA
Atochem (1993), Micronucleus test in Mice, CIT 9776 MAS
Atochem (1994), Hydrolysis studies on dimethylaminoethyl methacrylate, SA 006/94
CERI, Japan (1976), Chemicals Evaluation and Research Institute, unpublished data
CERI, Japan (1993), Report No. 21114 Chemicals Evaluation and Research Institute, unpublished
data
CERI, Japan (1997) Report No. 81115K, Chemicals Evaluation and Research Institute, unpublished
data
Clayton GD., Patty's Industrial Hygiene and Toxicology Vol. 2A, 2B, 2C, 2D, 2E, 2F, Toxicology
4th ed. New York, NY, John Wiley & Sons Inc., 3008, 1993-1994
Gage J.C., Brit. J. Industr. Med., 27, 1-18, 1970
Hanks C.T. et al., Cytoxic effects of resin compounds on cultured mammalian Fibroblasts, J. Dent.
Res., 70, 1450-1455, 1975
Izmerov, N.F. et al., Toxicometric Parameters of Industrial Toxic Chemical Under Single Exposure,
Moscow, Centre of International Projects, GKNT, 1982
JISHA (2000), Japan Industrial Safety and Health Association, unpublished data
Kirk-Othmer (1978-1984) Encyclopedia of Chemical Technology, 3rd Ed., 15, 367-369
MHW, Japan (1998) Ministry of Health and Welfare, Toxity Testing Reports of Environmental
Chemicals 6, 539-568
MOE, Japan (1997), Ministry of the Environment, unpublished data
Manabe. A. et al., Molphological changes of rabbit skin by application of Dentine Primer, Dent.
Mater. J., 9(2), 147-152, 1990
Mir G.N. et al., Toxicological and Pharmacological actions of Methacrylate Monomers III: Effects
on Respiratory and Cardiovascular Functions Anesthetized Dogs, J. Pharm. Sci., 63(3), 376-
381, 1974
UNEP Publications 27
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
Mir. G. N. et al., J. Pharmaceutical Sciences 1973, 62, 1258-1261
Mir. G. N., J. Pharmaceutical Sciences 1973, 62, 778-782
NTIS (Natl Tech Inf Serve) AD 277-689, 1986
Paulet G. et al., Arch. Mal. Prof. Med. Trav. Secur. Soc., 36(1-2), 58-60, 1975
Roehm (1977), unpublished report, Skin Irritation test, No. 77-023
Roehm (1978), unpublished report, Acute Oral Toxicity test in Rats, No. 78-061
Roehm (1988a), unpublished report, No. 88-041
Roehm (1988b), unpublished report, No. 88-048
Roehm (1989), unpublished report, Micronucleus test in Mice, No. 89-002
Rowell P.P. et al., Inhibition of cholin acetyltransferase by tertiary amino esters, Bioch.
Pharmacol. 25, 1093-1099, 1976
Schafer, E.W. et al (1983) The acute oral toxicity, repellency and hazard potential of 998 chemicals
to one or more species of wild and domestic birds, Arch. Environm. Contam. Toxicol., 12,
355-382, unpublished data
28 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
SIDS Dossier
Existing Chemical : ID: 2867-47-2
CAS No. : 2867-47-2
EINECS Name : 2-dimethylaminoethyl methacrylate
EINECS No. : 220-688-8
TSCA Name : 2-Propenoic acid, 2 -methyl-, 2-(dimethylamino)ethyl ester
Molecular Formula : C8H15NO2
Producer Related Part
Company : MITSUBISHI . GAS CHEMICAL CO., INC.
Creation date : 11.10.2001
Substance Related Part
Company : MITSUBISHI . GAS CHEMICAL CO., INC.
Creation date : 11.10.2001
Memo : MADAME SIAM 14
Printing date : 10.01.2002
Revision date :
Date of last Update : 10.01.2002
Number of Pages : 64
Chapter (profile) : Chapter: 1, 2, 3, 4, 5, 7
Reliability (profile) : Reliability: without reliability, 1, 2, 3, 4
Flags (profile) : Flags: without flag, confidential, non confidential, WGK (DE), TA-Luft (DE),
Material Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDS
UNEP Publications 29
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
1.0.1 OECD and Company Information
Type : lead organisation
Name : Mitsubushi Gas Chemical Company, Inc.
Partner :
Date :
Street : Mitsubishi Bldg. 5-2, Marunouchi 2-chom e, Chiyoda-ku
Town : 100-8324 Tokyo
Country : Japan
Phone : +81-3-3283-4821
Telefax : +81-6-6201-2857
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
09.01.2002
Type : cooperating company
Name : Atofina
Partner :
Date :
Street : 4-8, cours Michelet, La Defence 10
Town : F-92091 Paris La Defence Cedex
Country : France
Phone : +33 1 49 00 71 97
Telefax : +33 1 49 00 50 58
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
Type : cooperating company
Name : Degussa, Roehm GmbH & Co.
Partner :
Date :
Street : KG, Kischenallee,
Town : D-64293 Darmstadt
Country : Germany
Phone : +49 6151 184241
Telefax : +49 6151 183213
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
Type : cooperating company
Name : Mitsubishi Rayon Co., Ltd.
Partner :
Date :
Street : 1-6-41 Konan, Minato-ku,
Town : 108-8506 Tokyo
Country : Japan
Phone : +81 3 5495 3009
Telefax : +81 3 5495 3246
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
Type : cooperating company
30 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
Name : Mitsui Chemicals, Inc.
Partner :
Date :
Street : Kasumigaseki, Chiyoda-ku,
Town : 100-6070, Tokyo
Country : Japan
Phone : +81 3 3592 4340
Telefax : +81 3 3592 4236
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
Type : cooperating company
Name : Sanyo Chemical Industries, Ltd.
Partner :
Date :
Street : 11-1 Ikkyo, Nomoto -cho, Higashiyama-ku
Town : 605-0995 Kyoto
Country : Japan
Phone : +81 75 541 6362
Telefax : +81 75 531 2139
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
Type : cooperating company
Name : Ciba Specialty Chemicals Inc.
Partner :
Date :
Street : Klybeckstrasse 141
Town : CH-4002 Basel
Country : Switzerland
Phone : +41 61 636 55 29
Telefax : +41 61 636 78 78
Telex :
Cedex :
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
1.0.2 Location of Production Site
1.0.3 Identity of Recipients
1.1 General Substance Information
Substance type : organic
Physical status : liquid
Purity : % w/w
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
1.1.0 Details on template
1.1.1 Spectra
UNEP Publications 31
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
1.2 Synonyms
MADAME
Source : Mitsubushi Gas Chemical Company, Inc.
09.10.2001
2-(Dimethylamino)ethanolmethacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
2-(N,N-Dimethylamino)ethylmethacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
2-Dimethylaminoethyl methacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
2-Dimethylaminoethyl-2-methyl-propenoate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
2-Dimethylaminoethyl-2-methylpropenoate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
2-Propenoic acid, 2 -methyl, dimethylaminoethyl ester
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
beta-(N,N-Dimethylaminoethyl) methacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
beta-Dimethylaminoethyl methacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
DAM
Source : Mitsubushi Gas Chemical Company, Inc.
09.10.2001
Dimethylaminoethyl methacrylate
Source : SNF S.A. Saint-Etienne
Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
04.06.1998
DMAEMA
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
32 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
31.05.1994
Ethanol, 2-(dimethylamino), methacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
MADAME ; 2-(Dimethylamino)ethanolmethacrylat; 2-(N,N-Dimethylamino)ethylmethacrylat; 2 -
Dimethylaminoethyl-2-methyl-2-propenoat; 2-Dimethylamino-2-methylpropenoat;
Dimethylaminoethylmethacrylat; Ethanol, 2-(dimethylamino)-, methacrylat
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
08.06.1994
Methacrylic acid dimethylaminoethylester
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
Methacrylic acid, 2-(dimethylamino)ethyl ester
Source : SNF S.A. Saint-Etienne
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
04.06.1998
Methacrylsaueredimethylaminoethylester; N,N-Dimethylaminoethylmethacrylat; beta-(N,N-
Dimethylamino)ethylmethacrylat; beta-Dimethylaminoethylmethacrylat
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
22.12.1993
N,N-Dimethylaminoethyl methacrylate
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
1.3 Impurities
CAS-No : 108-01-0
EINECS-No : 203-542-8
EINECS-Name : 2-dimethylaminoethanol
Contents : < .5 % w/w
Remark : raw material
Source : Mitsubushi Gas Chemical Company, Inc.
12.12.2001
CAS-No : 80-62-6
EINECS-No : 201-297-1
EINECS-Name : methyl methacrylate
Contents : < .5 % w/w
Remark : raw material
Source : Mitsubushi Gas Chemical Company, Inc.
12.12.2001
1.4 Additives
CAS-No : 150-76-5
UNEP Publications 33
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
EINECS-No : 205-769-8
EINECS-Name : mequinol
Contents : .03 - .3 % w/w
Remark : stabilising agent
07.12.2001
1.5 Quantity
Remark : 8,000 t/year in Japan and 48,000 t/year world-wide in 2000
Source : Mitsubushi Gas Chemical Company, Inc.
08.01.2002
Production during the :
last 12 months
Import during the last :
12 months
Quantity : 10 000 - 50 000 tonnes in
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
1.6.1 Labelling
Labelling : as in Directive 67/548/EEC
Symbols : Xn
Nota : D
Specific limits : yes
R-Phrases : (21/22) Harmful in contact with skin and if swallowed
(36/38) Irritating to eyes and skin
(43) May cause sensitization by skin contact
S-Phrases : (2) Keep out of reach of children
(26) In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice
(28) After contact with skin, wash immediately with plenty of water...
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
08.01.2002
1.6.2 Classification
Classification : as in Directive 67/548/EEC
Class of danger : corrosive
R-Phrases : (21/22) Harmful in contact with skin and if swallowed
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
Classification : as in Directive 67/548/EEC
Class of danger : irritating
R-Phrases : (36/38) Irritating to eyes and skin
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
Classification : as in Directive 67/548/EEC
Class of danger :
R-Phrases : (43) May cause sensitization by skin contact
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
34 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
1.7 Use Pattern
Type : type
Category : Non dispersive use
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
Type : type
Category : Use in closed system
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
Type : industrial
Category : Chemical industry: used in synthesis
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
Type : industrial
Category : Polymers industry
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
Type : use
Category : Intermediates
Source : EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.02.2000
1.7.1 Technology Production/Use
1.8 Occupational Exposure Limit Values
Type of limit : Short Term Occupational Exposure Limit (OEL STEL)
Limit value : 1 ppm (6.43 mg/m3)
Remark : Proposed by ATOFINA's Occupational Limit Setting Committee)
Source : ATOFINA Paris La Defense France d`ELF
24.06.1998
Remark : No data available on Occupational Exposure Limit Values
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
08.06.1994
1.9 Source of Exposure
Remark : Occupational exposures at production sites may occur by the inhalation
route and dermal route.
The atmospheric concentration was measured at one production site [Japan
industrial Safety and Health Association (JISHA), 2000]. The monitored
data are shown below.
---------------------------------------------------------------------------------
Operation Monitoring Data Frequency Working time Max. EHE
Time/day hrs/timemg/kg/day
Drum Filling 0.19 mg/m3 1 0.50 1.70 x 10-3
( 0.03 ppm)
Drum Filling 0.19 mg/m3 1 0.05 1.70 x 10-4
( 0.03 ppm)
Drum Filling 0.19 mg/m3 1 0.025 8.48 x 10-3
( 0.03 ppm)
Total 1.95 x 10-3 mg/kg/day
----------------------------------------------------------------------------------
UNEP Publications 35
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
Air sample was suctioned at the breathing zone of the worker at the suction
rate of 0.4 L/min. for 5 min. and adsorbed through a collection can and
analyzed by GC.
As shown in Table, the monitored exposure concentrations were below
0.19 mg/m3 at the drum filling work, the maintenance work and the
sampling. The highest daily intake (respiratory EHEinh) for a worker (body
weight; 70 kg, respiratory volume; 1.25 m3/hr) assigned to the drum filling
work without protection is calculated as 1.70 x 10-3 mg/kg/day. The
duration of dermal exposure is assumed to be 0.50 hrs/day. EHEder for the
worker who implement all daily operation through hands is calculated as
7.50 x 10-2 mg/kg/day, assuming that the work is classified as non-
dispersive, direct handling, and contact level is incidental.
Workers are recommended to wear protective gear such as a mask, rubber
gloves and goggles to prevent exposure. Therefore EHEs are considered
to substantially lower than the calculated value.
Source : Japan Industrial Safety and Health Association (JISHA), 2000
08.01.2002
Remark : Batch process.
Transesterification based on methyl methacrylate.
Purification by distillation.
Heavy ends : incineration.
Effluents : biological treatment plant.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
08.06.1994
Remark : Emissions during production and processing are low as the product is
normally handled in closed systems. In the normal production process the
substance is not released into the waste water or the air. Release into the
waste water and the industrial sewage system during cleaning operations,
processing, destillation is low < 1 t/year. Emissions to the air during those
processes is well below 1 t/year.
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
26.05.1997 (49)
1.10.1 Recommendations/Precautionary Measures
1.10.2 Emergency Measures
1.11 Packaging
1.12 Possib. of Rendering Subst. Harmless
1.13 Statements Concerning Waste
1.14.1 Water Pollution
Classified by : KBwS (DE)
Labelled by : KBwS (DE)
Class of danger : 1 (weakly water polluting)
Source : Roehm GmbH Darmstadt
36 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
1. GENERAL INFORMATION Id 2867-47-2
Date 10.01.2002
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
12.11.2001
1.14.2 Major Accident Hazards
Legislation :
Substance listed : no
No. in directive :
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994
1.14.3 Air Pollution
Classified by : other: Roehm GmbH
Labelled by : other: Roehm GmbH
Number : 3.1.7 (organic substances)
Class of danger : III
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002
1.15 Additional Remarks
Remark : The product must be disposed of as special waste in
accordance with regulations for special waste.
Source : Roehm GmbH Darmstadt
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
30.05.1994 (50)
1.16 Last Literature Search
1.17 Reviews
1.18 Listings e.g. Chemical Inventories
UNEP Publications 37
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
2.1 Melting Point
Value : = -30 ?C
Sublimation :
Method : other: no data
Year :
GLP : no data
Test substance : no data
Source : HSDB (Hazardous substance data bank)
Flag : Critical study for SIDS endpoint
09.01.2002 (25)
Value : = -60 ?C
Sublimation :
Method : other: no data
Year :
GLP : no
Test substance : other TS: source; not available
09.01.2002 (37)
Value : = -36 ?C
Sublimation :
Method : other
Year :
GLP : no data
Test substance :
Remark : Beilstein 1998-1999
08.10.2001 (18)
Value : = -50 ?C
Sublimation :
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
Value : = -30 ?C
Sublimation :
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (24)
Value : <= -10 ?C
Sublimation :
Method : other: no data
Year :
GLP :
Test substance : other TS: source; not available
09.01.2002 (12)
38 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
2.2 Boiling Point
Value : = 186 ?C at 1013 hPa
Decomposition :
Method : other: not specified
Year :
GLP : no data
Test substance : source; not available
Source : Mitsubishi Gas Chemical Co., Inc.
10. 01. 2002 (11)
Value : = = 182 -190 ?C at 1013 hPa
Decomposition :
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (45)
Value : = 187 ?C at 1013 hPa
Decomposition :
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defens e
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (16)
Value : = 183 ?C at 1013 hPa
Decomposition :
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la DefenseEUROPEAN COMMISSION - European
Chemicals Bureau Ispra (VA)
10.01.2002 (40)
Value : = 186.3 ?C at 1013 hPa
Decomposition :
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Ullmann (1978) Ullmann's Encyclopaedie der technischen Chemie, Band
16: 609-614
10.01.2002
Value : = 186.8 ?C at 1013 hPa
Decomposition : ambiguous
Method : other
Year :
GLP : no data
Test substance :
Source : Pavlov et al (1972) J. Appl. Chem. USSR (Engl. Transl.) 45, 623-624
10.01.2002
UNEP Publications 39
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
2.3 Density
Type : density
Value : = .934 g/cm3 at 20?C
Method : other: no data
Year :
GLP : no data
Test substance : other TS: source; not available
Flag : Critical study for SIDS endpoint
09.01.2002 (12)
Type : density
Value : = .932 g/cm3 at 20?C
Method : other: no data
Year :
GLP : no data
Test substance : other TS: source; not available
09.01.2002 (37)
Type : density
Value : = .933 g/cm3 at 20?C
Method : other: not specified
Year :
GLP : no data
Test substance :
Remark : Vapour density: 6.54 kg/m3 at 20 degree C.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
Type : density
Value : = .93 g/cm3 at 25?C
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (26)
2.3.1 Granulometry
2.4 Vapour Pressure
Value : = 1.1 hPa at 25?C
Decomposition :
Method other (calculated)
Year : 1985
GLP : no
Test substance : other TS: source; not available
Source : SRC PhysProp Database
Flag : Critical study for SIDS endpoint
16.11.2001 (39)
1.33 hPa at 25?C
Value :
Decomposition :
Method
40 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
Year :
GLP : no data
Test substance : other TS: source; not available
09.01.2002 (12)
Value : = 1 hPa at 20?C
Decomposition :
Method other (calculated): not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
Value : = 5 hPa at 50?C
Decomposition :
Method other (calculated): not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
Value : = 13.3 hPa at 75?C
Decomposition :
Method other (calculated): not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (14)
2.5 Partition Coefficient
Log pow : = 1.13 at 25?C
Method OECD Guideline 107 "Partition Coefficient (n-octanol/water), Flask-shaking
Method"
Year : 1997
GLP : yes
Test substance : other TS: source; Wako Pure Chemical Industries,Ltd, Purity; 99.9 %
Remark : After partition equilibrium of the test substance was
established between n-octanol and water at three volume
ratios, the concentrations of the test substance of both
phase were determined with HPLC.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (12)
Log pow : = .3 at ?C
Method other (calculated)
Year :
GLP : no
Test substance :
Remark : Calculated according to Leo and Hansch (Freitexttype
method).
UNEP Publications 41
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (30)
Log pow : = .6 at ?C
Method other (calculated)
Year :
GLP :
Test substance :
Remark : Calculated according to Rekker.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (46)
2.6.1 Water Solubility
Value : = 106.1 g/l at 25 ?C
Qualitative :
Pka : at 25 ?C
PH :
Method : other: no data
Year : 1996
GLP : no data
Test substance : other TS: source; no data
Source : SRC PhysPro Database
Flag : Critical study for SIDS endpoint
16.11.2001 (32)
Value : at ?C
Qualitative :
Pka : 8.44 at 25 ?C
PH : at and ?C
08.10.2001 (10)
Value : = 500 g/l at 20 ?C
Qualitative :
Pka : at 25 ?C
PH : = 8 at and ?C
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (14)
100 g/l at ?C
Value :
Qualitative :
Pka : at 25 ?C
PH : at and ?C
Method :
Year :
GLP : no data
Test substance : other TS: source not available
09.01.2002 (12)
Remark : Soluble in all proportions at 20 癈
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
42 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
2.6.2 Surface Te nsion
2.7 Flash Point
68.6 ?C
Value :
Type : closed cup
Method : other
Year :
GLP : no data
Test substance : other TS: source; not available
Flag : Critical study for SIDS endpoint
09.01.2002 (37)
Value : = 57 ?C
Type : other
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (40)
Value : = 65 ?C
Type : open cup
Method : other
Year :
GLP : no data
Test substance :
Remark : Method: DIN 51 584 (A. PENSKY)
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
Value : = 73.9 ?C
Type : other: no data
Method : other
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (45)
Value : = 74 ?C
Type : closed cup
Method : other
Year :
GLP : no data
Test substance :
Remark : Method: DIN 51758
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (57)
2.8 Auto Flammability
UNEP Publications 43
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
2. PHYSICO-CHEMICAL DATA Id 2867-47-2
Date 10.01.2002
Value : = 255 ?C
Method : other: not specified
Year :
GLP : no data
Test substance :
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
2.9 Flammability
2.10 Explosive Properties
Result : other
Method : other: not speicfied
Year :
GLP : no data
Test substance :
Remark : Uncontrolled polymerization may occur to explosion
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
2.11 Oxidizing Properties
2.12 Additional Remarks
Remark : Henry's constant : 3.144 10E -2 pa m3/mol
Usually control the concentration of the additive and verifythe clearness of
the product
1 mg/m3 = 0.155 ppm
1 ppm = 6.431 mg/m3
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (16)
44 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
3. ENVIRONMENTAL FATE AND PATHWAYS Id 2867-47-2
Date 10.01.2002
3.1.1 Photodegradation
Type : air
Light source : Sun light
Light spect. : nm
Rel. intensity : based on Intensity of Sunlight
Conc. of subst. : at 25 ?C
Indirect photolysis
Sensitizer : OH
Conc. of sens. : 500000 molecule/cm3
Rate constant : = 9.918E -11. cm3/(molecule*sec)
Degradation : = 50 % after 4 hour(s)
Deg. Product :
Method : other (calculated)
Year :
GLP : no
Test substance :
Result : Photodegradation is estimated as ca.4 hrs, employing the following
calculation model.
T1/2(photo air OH)=0.693/(9.918E -11 * 5.0E5)/3600
Source : SRC PhysProp Database
Flag : Critical study for SIDS endpoint
12.12.2001 (32)
3.1.2 Stability in water
Type : abiotic
t1/2 pH4 : stable at 50 ?C
t1/2 pH7 : = 4.5 day at 25 ?C
t1/2 pH9 : = 3.3 hour(s) at 25 ?C
Deg. Product :
Method : OECD Guideline 111 "Hydrolysis as a Function of pH"
Year : 1993
GLP : no data
Test substance : other TS
Deg. Product : 108-01-0 203-542-8 2-dimethylaminoethanol
79-41-4 201-204-4 methacrylic acid
Method : -Preliminary Test
a) Water Temperature: 50 篊
b) Nominal Concentration: ca. 100 mg/L
c) pH: pH4
d) Number of Replicates: 2
e) Test Period: 5 days
f) Exposure Vessel Type: Glass Vial
-Final Test
a) Water Temperature: pH7; 50, 60 70 篊
pH9; 30, 40 篊
b) Nominal Concentration: ca. 100 mg/L
c) pH: pH7 and pH9
d) Number of Replicates: 2
Result : As a result of the preliminary test, 2-Dimethylaminoethyl methacrylate is not
decomposed at pH4 and 50篊 in water after 5 days.
Test substance : source: Wako Pure Chemical Industries, LTD.
purity: =99.9 %
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
UNEP Publications 45
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
3. ENVIRONMENTAL FATE AND PATHWAYS Id 2867-47-2
Date 10.01.2002
09.01.2002 (12)
Type : abiotic
t1/2 pH4 : at degree C
t1/2 pH7 : at degree C
t1/2 pH9 : at degree C
Remark : The substance was reported to be unstabel in water at 20癈. At 80癈 and
an initial concentration of 0.48 mM complete hydrolysis to methacrylic acid
and N,N -dimethylamino ethanol was observed. At pH 4 and temperatures
between 20 and 70癈 practically no hydrolysis was reported.
R閒. : Kazantsev, O.A., Zilberman E.N., Salov V.N., Krasnov V.L.;
Transformation of N,N-Dimethylaminoethylmethacrylate and acrylic acid in
aqueous solutions ; Zh. Prikl. Khim. 60(9), 2142-2145 (1987).
Result : Hydrolysis of dimethylaminoethyl methacrylate, studied in 2.5% HCl at 25
and 40 degree C (96h) was found negligible. In 2.5% NaOH solution, at 25
degree C, 80% of the ester was hydrolysed within 25 minutes.
Rate of alkaline hydrolysis of dimethylaminoethyl methacrylate in H2O and
aq. EtOH decreased with increasing EtOH concentration (0-60%).The
reaction was of the first order with respect to ester and the OH- ions.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (20) (21) (22)
3.1.3 Stability in soil
Type : other: hydrolysis
Radiolabel :
Concentration :
Soil temp. : degree C
Soil humidity :
Soil classif. :
Year :
Remark : The substance is expected to be susceptible to hydrolysis in particular in
alkaline soils.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994
3.2 Monitoring data
3.3.1 Transport between environmental compartments
3.3.2 Distribution
Media : air - biota - sediment(s) - soil - water
Method : Calculation according Mackay, Level III
Year : 2001
Method : Distributions were calculated with following factors
2-Dimethylaminoethyl
molecular weight: 157.21
melting point [篊]: -30
vapor pressure [Pa]: 110
water solubility [g/m3]: 106100
log Kow: 1.13
half life [h] in air: 4
46 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
3. ENVIRONMENTAL FATE AND PATHWAYS Id 2867-47-2
Date 10.01.2002
in water: 110
in soil: 110
in sediment: 330
temp. [C]: 25
Result : The potential environmental distribution of MADAME obtained from a
generic fugacity model Mackay level III under three emission scenarios is
shown in Table. The results show thatif MADAME is released into water, it
is unlikely to migrate into other compartments. When MADAME is released
to air, it is likely to be transported both to water and soil.
Compartment Relese 100% Relese 100% Relese 100%
to air to water to soil
Air 72.1% 0.0% 0.1%
Water 13.6% 99.7% 5.7%
Soil 14.2% 0.0% 94.2%
Sediment 0.0% 0.2% 0.0%
Flag : Critical study for SIDS endpoint
Source : Mitsubushi Gas Chemical Company, Inc., unpublished data
12.12.2001
Media : air - biota - sediment(s) - soil - water
Method : Calculation according Mackay, Level I
Year : 1993
Result : Air : 1.09 %
Water : 98.86 %
Soil : 0.02 %
Sediment : 0.02 %
Suspended
Aquatic mat. : 0 %
Biota : 0%
Fugacity : 4.44 10E7 Pa
Compound properties and parameters for calculation :
molecular weight : 157.2 g/mol
aqueous solubility : 510E5 g/m3
vapour pressure : 1 10E2 Pa
Henry's constant : 3.144 10E2 Pa m3/mol
log Pow : 0.45
Temperature : 20癈
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994
3.4 Mode of degradation in actual use
3.5 Biodegradation
Type : aerobic
Inoculum : predominantly domestic sewage
Concentration : 20mg/l related to
related to
Contact time :
Degradation : = 95.3 % after 28 day
Result : readily biodegradable
Deg. Product :
UNEP Publications 47
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
3. ENVIRONMENTAL FATE AND PATHWAYS Id 2867-47-2
Date 10.01.2002
Method : OECD Guideline 301 E "Ready biodegradability: Modified OECD Screening
Test"
Year : 1980
GLP : no data
Test substance :
Remark : Method: also EG-Richtlinie 84/449/EWG, Teil C.3 im EG-Amtsblatt L251,
ISO 7824 (1984).
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : Concentration: 20 mg/l related to BOD.
Flag : Critical study for SIDS endpoint
09.01.2002 (47)
Deg. Product : yes
Method :
Year :
GLP : yes
Test substance :
Deg. Product : 108-01-0 203-542-8 2-dimethylaminoethanol
79-41-4 201-204-4 methacrylic acid
Result : MADAME becomes Methacrylic acid (MAA) and
2-Dimethylaminoethanol (DMAE) by hydrolysis. Their biodegradation data
are shown below.
Methacrylic acid
-Method: MITI (I) method (1974), corresponding to the OECD 301C (1981).
-Test Substance:
a)Degree of Purity: >=99.0%
-Concentration: =100mg/L related to Test substance
-Test Conditions:
a)Water Temperature: 24-26 篊
b)Inoculum: standardized activated sludge, 30 mg/L assuspended solid
c)Aeration: aerated by atmospheric air
d)Exposure Vessel Type: 300 mL culture bottle
e)Number of Replicate: 3
-Degradation: = 89-94% after 14 days (readily biodegradable)
-Year: 1993
-Reference: CERI, Japan, Report No. 21114, Chemicals Evaluation and
Research Institute, Japan, unpublished data.
2-Dimethylaminoethanol
-Method: MITI (I) method (1974), corresponding to the OECD 301C (1981).
-Concentration: =100mg/L related to Test substance
-Degradation: = 60.5% after 14 days (readily biodegradable)
-Year: 1976
-Reference: CERI, Japan, Chemicals Evaluation and Research Institute,
Japan, unpublished data.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (11)
3.6 BOD5, COD or BOD5/ COD ratio
3.7 Bioaccumulation
3.8 Additional remarks
48 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
4.1 Acute/prolonged toxicity to fish
Type : semistatic
Species : Oryzias latipes (Fish, fresh water)
Exposure period : 96 hour(s)
Unit : mg/l
Analytical monitoring : yes
LC50 : = 19.1
Method : OECD Guideline 203 "Fish, Acute Toxicity Test"
Year : 1997
GLP : yes
Test substance : other TS: Wako Pure Chemical Industries,Ltd., Purity 99.0 %, Lot No.
WTL5063
Method : -Test Organisms:
a) Size (length and weight): 2.1 cm (2.0 - 2.3 cm) in length; 0.13 g (0.10 -
0.20 g) in weight
b) Age: Not described
c) Any pretreatment: Acclimated for several days before testing, any
groups showing > 5 % mortality were not used for testing. Not fed for 24
hours before the test started.
d) Supplier/Source: SANKYO LAB SERVICE CO., LTD. (JAPAN)
-Test Conditions:
a) Dilution Water Source: Not described
b) Dilution Water Chemistry: Not described
c) Exposure Vessel Type: 3 L test solution in a 3 L Glass Beaker
d) Nominal Concentrations (as mg/L): 0, 10, 18, 32, 56 and 100
e) Vehicle/Solvent and Concentrations: Not used
f) Stock Solutions Preparations and Stability: No stock solution was
prepared for the tests. The test substance was directly dissolved in 3 L-
dilution water.
g) Number of Replicates: 1
h) Fish per Replicates: 10
i) Renewal Rate of Test Water: Every 24 hours because the test substance
is not stable in water
j) Water Temperature: 23.0 - 25.0 篊
k) Light Condition: 16:8 hours, light-darkness cycle
l) Feeding: No
m) Water hardness: 30.3 mg/L
Method, cont. : - Analytical Procedure: The tested concentrations were measured at 0 hour
and 24 hours (before exchange of test solution) by High Performance Liquid
Chromatography method.
-Statistical Method:
a) Data Analysis: ProbitMethod for LC50
b) Method of Calculating Mean Measured Concentrations (i.e.arithmetic
mean, geometric mean, etc.): Geometric Mean
Result Measured Concentrations (as mg/L): 6.47, 10.8, 14.2, 23.0 and 35.0 after
24 h exposure (65 - 35 % of the nominal concentrations)
Measured Concentration of MADAME during a 24-hour Exposure Test
Condition (Fish, 96h)
UNEP Publications 49
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Nominal Measured Conc. (mg/L) Percent
Conc. 0 Hour 24 Hour Geometric of
mg/L new o ld Mean Nominal
Control N.D. N.D. N.D.
10 9.20 4.55 6.47 65
18 17.0 6.86 10.8 60
32 24.1 8.37 14.2 44
56 41.3 12.8 23.0 41
100 88.7 13.8 35.0 35
new: freshly prepared test solutions
old: test solutions after 24 hours exposure period
- Water chemistry in test (pH and DO): pH 7.22 - 7.61 (control), DO 5.31 -
8.70 mg/L
-Effect Data(mortality):
96hr LC50 =19.1mg/L (95% Confidence Interval:15.8-23.5mg/L)
- Cumulative Mortality:
Nominal
Concentration Cumulative N umber of Dead
mg/L 24hr 48hr 72hr 96hr
Control 0 0 0 0
10 0 0 0 0
18 0 0 1 1
32 0 0 1 2
56 3 3 4 6
100 10 10 10 10
Result, cont. : -Other Effect
Symptom of Toxicity Observed in Orange killfish (Oryzias latipes)
Nominal
Concentration Symptom
mg/L 24hr 48hr 72hr 96hr
Control Normal Normal Normal Normal
10 Normal Normal Normal Normal
18 Normal Normal Normal Normal
32 Convulsion Convulsion Convulsion Rolling
Rolling
56 Convulsion Convulsion Convulsion Normal
Rolling
100 All dead
- Calculation of toxic values: Based on the measured concentrations,
because the measured concentrations were < 80 % of the nominal
concentrations
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (38)
Type : semistatic
Species : Oryzias latipes (Fish, fresh water)
Exposure period : 14 day
Unit : mg/l
50 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Analytical monitoring : yes
LC0 : = 1.36
LC50 : = 5.26
Method : OECD Guideline 204 "Fish, Prolonged Toxicity Test: 14-day Study"
Year : 1997
GLP : yes
Test substance : other TS: Wako Pure Chemical Industries,Ltd., Purity 99.0 %, Lot No.
WTL5063
Method -Test Organisms:
a) Size (length and weight): 2.12 cm (2.0 - 2.3 cm) in length; 0.122 g (0.101
- 0.152 g) in weight
b) Age: Not described
c) Any pretreatment: Acclimated for several days before testing, any
groups showing > 5 % mortality were not used for testing. Not fed for 24
hours before the test started.
d) Supplier/Source: SANKYO LAB SERVISE CO., LTD. (JAPAN)
-Test Conditions:
a) Dilution Water Source: Not described
b) Dilution Water Chemistry: Not described
c) Exposure Vessel Type: 5 L test solution in a 5 L-Glass Beaker
d) Nominal Concentrations (as mg/L): 0, 2.2, 4.6, 10, 22 and 46
e) Vehicle/Solvent and Concentrations: Not used
f) Stock Solutions Preparations and Stability: No stock solution was
prepared for the tests. The test substance was directly dissolved in 5 L-
dilution water.
g) Number of Replicates: 1
h) Fish per Replicates: 10
i) Renewal Rate of Test Water: Every 24 hours because the test substance
is not stable in water
j) Water Temperature: 23.0 - 25.0 篊
k) Light Condition: 16:8 hours, light-darkness cycle
l) Feeding: No
m) Water hardness: 30.3 mg/L
- Analytical Procedure: The tested concentrations were measured at 0 hour,
7 days and 13 days (after exchanges ofthe test solution, and after 24
hours) by High Performance Liquid Chromatography method.
-Statistical Method:
a) Data Analysis: Probit Method for LC50
b) Method of Calculating Mean Measured Concentrations (i.e.arithmetic
mean, geometric mean, etc.): Time-weighted Mean measured concentration
during 14 days
Result - Measured Concentrations (as mg/L): 1.36, 2.96, 5.86, 10.1
and 21.0 (Time-weighted Mean during 14 days, 62 - 46 % of
the nominal concentrations)
Measured Concentration of MADAME during a 24-hour Exposure Test
Condition (Fish, 14d)
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 0 day 1 day
mg/L new old new old
Control N.D. N.D. ----- ----.
2.2 1.87 1.05 85 48
4.6 4.57 2.15 99 47
10 10.0 4.16 100 42
22 18.1 6.19 82 28
46 46.4 8.64 101 19
UNEP Publications 51
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 7 day 8 day
mg/L new old new old
Control N.D. N.D. ----- ----.
2.2 1.81 0.97 82 44
4.6 4.23 1.99 92 43
10 9.36 3.07 94 31
22 18.7 4.28 85 19
46 44.7 6.19 97 13
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 13 day 14 day
mg/L new old new old
Control N.D. N.D. ----- ----.
2.2 1.73 0.98 79 45
4.6 3.95 1.75 86 38
10 9.16 2.68 92 27
22 19.3 3.73 88 17
46 ----- ----- ---- ----
Result, cont. : Nominal Time-weighted Mean
Conc. during14 day
mg/L mg/L
Control -----.
2.2 1.36
4.6 2.96
10 5.86
22 10.1
46 20.0
new: freshly prepared test solutions
old: test solutions after 24 hours exposure period
- Water chemistry in test (pH and DO): pH 7.27 - 7.80
(control), pH 7.58 - 8.80 (46 mg/L), DO 5.31 - 8.70 mg/L
-Effect Data(mortality)
14 days LC50 = 5.26mg/L(95% Confidence Interval:13.87-7.03 mg/L)
14 days LC0 = 2.96mg/L
- Cumulative Mortality:
Nominal
concentration Cumulative Number of Dead
mg/L 1d 2d 3d 4d 5d 6d 7d 8d 9d 10d 11d 12d 13d 14d
Control 0 0 0 0 0 0 0 0 0 0 0 0 0 0
2.2 000000 000 0 0 0 0 0
4.6 000000 000 0 0 1 2 2
10 111122 222 3 5 5 5 5
22 112455 677 8 8 9 9 9
46 7 8 9 9 9 9 9 10 10 10 10 10 10 10
-Other Effect
Symptom of Toxicity Observed in Orange killfish (Oryzias latipes)
52 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Nominal
Concentration Symptom
mg/L 0d 7d 10d 14d
Control Normal Normal Normal Normal
2.2 Normal Normal Normal Normal
4.6 Normal Normal Normal Normal
10 Normal Anorexia Anorexia Aorexia
dull behavior
Result, cont. 22 Convulsion Anorexia Anorexia Anorexia
(light) dull behavior dull behavior dull behavior
46 Convu lsion Anorexia all dead
Dead(6 fishes) dull behavior
Mean Fish Weight and Length (14 days)
Nominal
Concentration
mg/L weight(mg/L) length(mm)
Control 126.9 21.3
2.2 138.5 21.8
4.6 118.6 21.1
10 139.0 22.8
22 174 24.0
46 - -
- Calculation of toxic values: Based on the measured concentrations,
because the measured concentrations were < 80 % of the nominal
concentrations
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (38)
Type :
Species : other: Osteichtyes (Common Name: Bony fish superclass)
Exposure period : 72 hour(s)
Unit : mg/l
Analytical monitoring :
LC50 : = 150
Method :
Year : 1975
GLP :
Test substance :
11.12.2001 (1)
Type :
Species : Carassius auratus (Fish, fresh water)
Exposure period : 72 hour(s)
Unit : mg/l
Analytical monitoring : no data
LC50 : = 139.5
Method : other
Year :
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
UNEP Publications 53
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
08.12.1993 (43)
Type :
Species : Leuciscus idus (Fish, fresh water)
Exposure period : 48 hour(s)
Unit : mg/l
Analytical monitoring :
LC0 : = 300
LC50 : = 331 - 592
LC100 : = 600
Method : other
Year :
GLP : yes
Test substance : as prescribed by 1.1 - 1.4
Remark : Method: DIN 38412, Teil 15.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
11.12.2001 (51)
4.2 Acute toxicity to aquatic invertebrates
Type : semistatic
Species : Daphnia magna (Crustacea)
Exposure period : 48 hour(s)
Unit : mg/l
Analytical monitoring : yes
NOEC : = 18.7
EC50 : = 33
Method : OECD Guideline 202, part 1 "Daphnia sp., Acute Immobilisation Test"
Year : 1997
GLP : yes
Test substance : other TS: Wako Pure Chemical Industries,Ltd., Purity 99.0 %, Lot No.
WTL5063
Method : - Test Organisms:
a) Age: < 24 hours old
b) Supplier/Source: National Institute for Environmental
Studies (JAPAN)
- Test Conditions:
a) Dilution Water Source: Not described
b) Dilution Water Chemistry: Not described
c) Exposure Vessel Type: 100 mL test solution in a 100 mLGlass Beaker
d) Nominal Concentrations (as mg/L): 0, 18, 32, 56, 100, 180 and 320
e) Vehicle/Solvent and Concentrations: Not used
f) Stock Solutions Preparations and Stability: For 320 mg/L and 180 mg/L
test concentrations, the test substance were dissolved in each 100 mL-
dilution water. For other test concentrations, 1.0 % stock solution was
prepared.
g) Number of Replicates: 4
h) Individuals per Replicates: 5
i) Renewal Rate of Test Water: Every 24 hours because the test substance
is not stable in water
j) Water Temperature: 19.7 - 20.0 篊
k) Light Condition: 16:8 hours, light-darkness cycle
l) Feeding: No
m) Water hardness: 30.3 mg/L
- Analytical Procedure: The tested concentrations were measured at 0 hour
54 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
and 24 hours (before exchanges of the test solution) by High Performance
Liquid Chromatographymethod.
- Statistical Method:
a) Data Analysis: Probit Method for EC50
b) Method of Calculating Mean Measured Concentrations (i.e.arithmetic
mean, geometric mean, etc.): Geometric Mean
Remark : NOEC was determined based on immobility.
Result : - Measured Concentrations (as mg/L): 10.5, 18.7, 29.7, 43.7, 70.4 and 119
(58 - 37 % of the nominal concentrations)
Measured Concentration of MADAME during a 24-hour Exposure Test
Condition (Daphnia magna, 48h)
Nominal Measured Conc. (mg/L) Percent
Conc. 0 Hour 24 Hour Geometric of
mg/L new old Mean Nominal
Control N.D. N.D. N.D.
18 15.0 7.33 10.5 58
32 30.1 11.6 18.7 58
56 51.7 17.0 29.7 53
100 76.2 25.0 43.7 44
180 145 34.2 70.0 39
320 285 49.4 119 37
- Water chemistry in test (pH and DO): pH 7.52 - 7.67 (control), DO 8.43 -
8.93 mg/L
-Effect Data(immobilization):
48hr EC50 = 33mg/L
48hr NOEC = 18.7mg/L
Cumulative Number of Immobilized Parental Daphnia
Nominal
Concentration Cumulative Number of Immobilized Daphnia
magna
mg/L 24hr 48hr
Control 0 0
18 0 0
32 0 0
56 0 4
100 6 20
180 12 20
320 20 20
the values including dead Daphnia magna
- Calculation of toxic values: Based o n the measured concentrations,
because the measured concentrations were < 80 % of the nominal
concentrations.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (38)
Type :
Species : Daphnia magna (Crustacea)
Exposure period : 48 hour(s)
Unit : mg/l
Analytical monitoring : no
EC50 : = 53
Method : ISO 6341 15 "Water quality - Determination of the inhibition of the mobility
of Daphnia magna Straus (Cladocera, Crustacea)"
UNEP Publications 55
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Year : 1989
GLP : yes
Test substance : as prescribed by 1.1 - 1.4
Remark : EC(I)50, 24 h = 73 mg/l
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
08.12.1993 (15)
4.3 Toxicity to aquatic plants e.g. algae
Species : Selenastrum capricornutum (Algae)
Endpoint : biomass
Exposure period : 72 hour(s)
Unit : mg/l
Analytical monitoring : yes
NOEC : = 18
EC50 : = 41.6
Method : other: OECDGuideline 201
Year : 1997
GLP : yes
Test substance : other TS: Wako Pure Chemical Industries,Ltd., Purity 99.0 %, Lot No.
WTL5063
Method : - Test Organisms:
a) Method of Cultivation: Subculturing in OECD medium until use
b) Stain Number: Not described
c) Supplier/Source: Not described
- Test Conditions:
a) Medium: OECD medium
b) Exposure Vessel Type: 100 mL Medium in a 300 mL Conical Flask
c) Nominal Concentrations (as mg/L): 0, 10, 18, 32, 56 and 100
d) Vehicle/Solvent and Concentrations: Not used.
e) Stock Solutions Preparations and Stability: The concentration of the test
substance in the stock solution was 10,000 mg/L.
f) Number of Replicates: 3
g) Initial Cell Number: 10,000 cells/mL
h) Water Temperature: 22.8 - 23.2 篊
i) Light Condition: 4,000 - 5,000 lux, continues
m) Water hardness: 30.3 mg/L
- Analytical Procedure: The tested concentrations were measured at the
start (0 hour) and the end (72 hours) of the tests by High Performance
Liquid Chromatography method.
- Statistical Method:
a) Data Analysis: Not described
b) Method of Calculating Mean Measured Concentrations (i.e.arithmetic
mean, geometric mean, etc.): Not calculated
Remark : NOEC was determined based on growth inhibition.
The hydrolysis rate is extremely large at higher pH (half life: 4.54days at
pH7 and 3.31 hours at pH9). MADAME is hydrolyzed to Methaclylic acid
(MAA) and 2-Dimethylaminoethanol (DMAE). There is some possibility of
effects of MAA or DMAE instead of MADAME on the aquatic organisms.
Result : Measured Concentrations (as mg/L): 72 hours; N.D., 0.07,0.30, 0.86 and
2.18 (0.39 - 2.18 % of nominal concentrations)
Measured Concentration during a 72-hour exposure to
56 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Selenastrum capricornutum
Nominal Measured Conc. (mg/L)
Conc. 0 Hour Percent of 72 Hour Percent of
mg/L Nominal Nominal
Control N.D. . N.D.
10 8.82 88.2 N.D. -----
18 15.2 84.4 0.07 0.39
32 25.9 80.9 0.30 0.94
56 48.3 86.3 0.86 1.54
100 83.4 83.4 2.18 2.18
- Water chemistry in test (pH and DO): pH 9.03 - 9.25 at the start of the test,
pH 7.90 - 9.13 at the end of the test
-Effect Data:
area method
EbC50(0-72hr) = 41.6mg/L (95% Confidence Interval: 37.3-46.5mg/L)
NOEC = 18mg/L
rate method
ErC50(24-48hr) = 69.7mg/L (95% Confidence Interval: 57.1-85.1mg/L)
NOEC = 56mg/L
ErC50(24-72hr) = 84.0mg/L (95% Confidence Interval: 74.5-94.8mg/L)
N OEC = 32mg/L
- Mean Cell Concentration of Each Flask (as cells/mL)
Nominal Cell density of Selenastrum capricornutum
Concentration Cell Density (x 10,000 cells/mL)
mg/L 0hr 24hr 48hr 72hr
Control 1.0 3.6 18.7 81.6
10 1.0 3.5 15.2 83.9
18 1.0 4.0 16.3 80.3
32 1.0 2.8 12.8 53.7
56 1.0 2.3 6.6 30.2
100 1.0 1.0 0.361 2.9
- Growth Curves: Log phase during the test period
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (38)
4.4 Toxicity to microorganisms e.g. bacteria
Type : aquatic
Species : Pseudomonas putida (Bacteria)
Exposure period : 18 hour(s)
Unit : mg/l
Analytical monitoring : no data
EC10 : = 42.7
Method : other
Year :
GLP : no data
Test substance :
Remark : Method: Bringmann-Kuehn.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (48)
4.5.1 Chronic toxicity to fish
UNEP Publications 57
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
4.5.2 Chronic toxicity to aquatic invertebr ates
Species : Daphnia magna (Crustacea)
Endpoint : reproduction rate
Exposure period : 21 day
Unit : mg/l
Analytical monitoring : yes
NOEC : = 4.35
EC50 : = 7.86
LC50 : = 16.6
Method : other: OECD Guideline 211
Year : 1997
GLP : yes
Test substance : other TS: Wako Pure Chemical Industries,Ltd., Purity 99.0 %, Lot No.
WTL5063
Method : - Test Organisms:
a) Age: < 24 hours old
b) Supplier / Source: National Institute for Environmental Studies (JAPAN)
- Test Conditions:
a) Dilution Water Source: Not described
b) Dilution Water Chemistry: Not described
c) Exposure Vessel Type: 80 mL test solution in a 100 mLGlass Beaker
d) Nominal Concentrations (as mg/L): 0, 0.632, 2.0, 6.32, 20 and 63.2
e) Vehicle/Solvent and Concentrations: Not used
f) Stock Solutions Preparations and Stability: 1.0% stack solution was
prepared.
g) Number of Replicates: 10
h) Individuals per Replicates: 1
i) Renewal Rate of Test Water: Every 24 hours because the test substance
is not stable in water
j) Water Temperature: 20.4 - 21.0 篊
k) Light Condition: 16:8 hours, light-darkness cycle, not more than 1,200
lux
l) Feeding: 0.18 mg carbon/day/individual (Chlorella Vulgaris)
m) Water hardness: 30.3 mg/L
- Analytical Procedure: The tested concentrations were measured before
and after renewal of the test water by High Performance Liquid
Chromatography method. Total of 8 times
were measured during the test period.
- Statistical Method:
a) Data Analysis: Probit Method for LC50, Logit Method for EC50
b) Method of Calculating Mean Measured Concentrations (i.e.arithmetic
mean, geometric mean, etc.): Time-weighted Mean measured concentration
during 21 days
Remark : NOEC was determined based on the cumulative number of juveniles
produced per adult alive for 21 days.
Result : Effect: reproduction
- Measured Concentrations (as mg/L): 0.479, 1.44, 4.35, 11.2 and 33.8 (76 -
54 % of the nominal concentrations)
Measured Concentration of MADAME during a 21-day Exposure of Daphnia
magna under Semi-Static Test Condition
58 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 0 day 1 day
mg/L new old new old
Control N.D. N.D. ----- ----.
0.632 0.695 0.343 110 54
2.0 1.90 0.97 95 49
6.32 6.14 2.79 97 44
20 14.6 6.07 73 30
63.2 60.0 16.9 95 27
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 7 day 8 day
mg/L new old new old
Control N.D. N.D. ----- ----.
0.632 0.641 0.350 101 55
2.0 1.83 1.02 92 51
6.32 5.96 2.92 94 46
20 16.1 7.07 81 35
63.2 58.3 17.2 92 27
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 14 day 15 day
mg/L new old new old
Control N.D. N.D. ----- ----.
0.632 0.583 0.383 92 61
2.0 1.98 1.14 99 57
6.32 6.08 3.16 96 50
20 18.6 7.31 93 37
63.2 ----- ------ ----- -----
Nominal Measured Conc. (mg/L) Percent of Nominal
Conc. 20 day 21 day
mg/L new old new old
Control N.D. N.D. ----- ----.
0.632 0.582 0.359 92 57
2.0 1.94 1.09 97 55
6.32 6.15 3.04 97 48
20 18.3 7.15 92 36
63.2 ----- ------ ----- -----
Result, cont. Nominal Time-weighted Mean
Conc. during14 day
mg/L mg/L
Control -----.
0.632 0.479
2.0 1.44
6.32 4.35
20 11.2
63.2 33.8
new: freshly prepared test solutions
old: test solutions after 24 hours after freshly prepared
- Water chemistry in test (pH and DO): pH 7.63 - 7.74 (control), pH 8.70 -
8.83 (63.2 mg/L), DO 7.56 - 8.70 mg/L,Hardness 29.5 - 39.3
-Effect Data(reproduction):
21days LC50 = 16.6mg/L (parental mortality)
UNEP Publications 59
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
21days EC50 = 7.86mg/L
21days NOEC = 4.35mg/L
- Cumulative Number of Dead Parental Daphnia
Nominal
Concentration Cumulative Number of Dead Parental Daphnia
mg/L 1d 7d 14d 21d
Control 0 0 0 0
0.632 0 0 0 0
2.0 0 0 0 0
6.32 0 0 0 0
20 0 0 0 0
63.2 0 9 10 10
- Time (days) of the First Production of Young: Mean; Control (11.2), 0.632
mg/L (11.3), 2.0 mg/L (12.1), 6.32 mg/L (11.7), 20 mg/L (11.8) and 63.2
mg/L (-)
- Cumulative numbers of juveniles produced per adult alive for 21 days
Result, cont. Vessel No.Control, Nominal concentration, mg/L
(Measured Concentration, mg/L)
0.632 2.0 6.32 20 63.2
(0.479) (1.44)(4.35) (11.2) (33.8)
1 63 61 44 56 16 D
2 66 62 47 71 19 D
3 82 68 77 70 6 D
4 59 84 61 66 1 D
5 83 85 48 65 3 D
6 74 61 70 48 9 D
7 65 68 63 49 11 D
8 71 60 54 80 4 D
9 50 76 55 44 2 D
10 65 51 53 72 -- D
Mean 67.8 67.6 57.2 62.1 7.9 --
S.D. 10.1 11.0 10.5 12.1 6.4 --
Signifucant ratio * *
D: Were not calculated because the parental Daphnia magna was dead
during a 21-days testing period.
*1: Indicate a significant difference by Dunnett mulitiple comparioson
procedure
- Calculation of toxic values: Based on the measured concentrations,
because some data of the measured concentrations were < 80 % of the
nominal concentrations.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (38)
4.6.1 Toxicity to soil dwelling organisms
4.6.2 Toxicity to terrestrial plants
4.6.3 Toxicity to other Non-Mamm. terrestrial species
60 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. ECOTOXICITY Id 2867-47-2
Date 10.01.2002
Species : other: Agelais Phoenicus
Endpoint : mortality
Exposure period : 18 hour(s)
Unit : mg/kg bw
LD50 : = 98
Method : other
Year :
GLP :
Test substance :
Remark : Repellency value (R50)= 1.0
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : Method: wild-trapped birds were preconditionned to captivity for 2 to 6
weeks and were usually dosed by gavage with solutions or suspensions of
the test chemical in propylene glycol, according to methods described by
DeCino et al. (1966), Schafer (1972) and Schafer et al. (1967).
LD50 values were calculated by the method of Thompson
(1948), Thompson and Weil (1952) and Weil (1952).
Repellency tests were conducted by the methods of starr et al. (1964) and
Schafer and Brunton (1971), and R50's were calculated either by the
method of Litchfield and Wilconxin (1949) or Thompson and weil (1952).
Bird species: Agelaius phoeniceus (Red-winged blackbird).
10.01.2002 (56)
4.7 Biological effects monitoring
4.8 Biotransformation and kinetics
4.9 Additional remarks
UNEP Publications 61
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
5.1.1 Acute oral toxicity
Type : LD50
Species : rat
Strain : Crj: CD(SD)
Sex : male/female
Number of animals : 10
Vehicle : other: Corn Oil
Value : > 2000 mg/kg bw
Method : OECD Guideline 401 "Acute Oral Toxicity"
Year : 1998
GLP : yes
Test substance : other TS: 99.9% purity, Sanyo-Kasei Co.
Remark : There were no deaths of animals in the 2000 mg/kg dosed group. At
necropsy, raised patches in the forestoma were observed in males of the
ch
2000 mg/kg group. Histopathologically, papillomatous hyperplasia in the
forestomach was apparent.
Result : A single oral toxicity test revealed an LD50 value of above 2000 mg/kg bw
for this chemical in both sexes.
Test condition : Doses; 0 (vehicle), 500, 1000, 2000 mg/kg bw.
Vehicle; Corn oil.
Administration; One administration
Number of animals: 5 males/5 females
Observation period; 14 days
Source : MHW, Japan: 1998
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
12.12.2001 (33)
Type : LD50
Species : rat
Strain :
Sex :
Number of animals :
Vehicle :
Value : = 1751 mg/kg bw
Method : other: not specified
Year : 1982
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (23)
Type : LD50
Species : rat
Strain :
Sex :
Number of animals :
Vehicle :
Value : = 2659 mg/kg bw
Method : other: not specified
Year : 1978
GLP : no data
Test substance : as prescribed by 1.1 - 1.4
Remark : Density: 0.933 g/cm3
Source : Roehm,
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (54)
62 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
Type : LD50
Species : rat
Strain :
Sex :
Number of animals :
Vehicle :
Value : = 1550 mg/kg bw
Method : other: not specified
Year :
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (27)
5.1.2 Acute inhalation toxicity
Type : LC50
Species : rat
Strain :
Sex :
Number of animals :
Vehicle :
Exposure time : 4 hour(s)
Value : = .62 mg/l
Method : other
Year : 1982
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (23)
Type : LC50
Species : mouse
Strain :
Sex :
Number of animals :
Vehicle :
Exposure time : 2 hour(s)
Value : = 1.8 mg/l
Method : other
Year : 1982
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (23)
5.1.3 Acute dermal toxicity
Type : LD50
Species : rat
Strain : Sprague-Dawley
Sex : male/female
Number of animals : 10
Vehicle : undilute d
UNEP Publications 63
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
Value : > 2000 mg/kg bw
Method : OECD Guideline 402 "Acute dermal Toxicity"
Year : 1992
GLP : yes
Test substance : as prescribed by 1.1 - 1.4
Result : Within 72 hrs of application of the test substance, hypokinesia, sedation and
dyspnea were observed. Local signs of marked irritations were noted during
the study. The body weight gain of the animals was not influenced by the
treatment. No deaths occured at the dose level of 2000 mg/kg. The
macroscopic exa mination revealed no abnormalities in the animals
sacrificed at the end of the study. Signs of cutaneous irritation had eversed.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : The test subs tance was applied in its original form directly to the skin of test
animals at a dose level of 2000 mg/kg. After 24 hrs under semi-occlusive
dressing, no residual test substance was observed.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (2)
Type : LD50
Species : rabbit
Strain :
Sex :
Number of animals :
Vehicle :
Value : > 3000 mg/kg bw
Method : other: not specified
Year :
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (27)
5.1.4 Acute toxicity, other routes
Type : LD50
Species : rat
Strain :
Sex :
Number of animals :
Vehicle :
Route of admin. : i.p.
Exposure time :
Value : = 97 mg/kg bw
Method : other
Year : 1973
GLP : no data
Test substance : as prescribed by 1.1 - 1.4
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (28)
Type : LD50
Species : rat
Strain :
Sex :
Number of animals :
64 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
Vehicle :
Route of admin. : i.p.
Exposure time :
Value : = 310 mg/kg bw
Method : other: not specified
Year :
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (42)
Type : LD50
Species : mouse
Strain :
Sex :
Number of animals :
Vehicle :
Route of admin. : i.p.
Exposure time :
Value : = 25 mg/kg bw
Method : other: not specified
Year :
GLP : no data
Test substance : no data
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (41)
5.2.1 Skin irritation
Species : rabbit
Concentration : undiluted
Exposure :
Exposure time : 24 hour(s)
Number of animals : 4
PDII : 8
Result : corrosive
EC classification : corrosive (causes burns)
Method : other
Year : 1980
GLP : no data
Test substance : as prescribed by 1.1 - 1.4
Remark : Severe erythema, oedema and necrosis were exhibited 24 hrs following
application. Reactions persisted to 72 hrs. For all animals and for both of
intact skin and abraded skin, maximum score of 4 was marked in the
erythema and oedema rating, therefore a Primary Irritation Score of 8 was
obtained.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : The method described in the Federal Hazardous Substances Labelling Act
Regulations, Section 191.11, published in the Federal Register - 29 F.R.
13009, 1964.
A 0.5 mL sample of the test material was applied to areas of intact and
abraded areas of skin. These areas were then occuluded with square
surgical gauge patches, each measuring 1 inch x 1 inch. After 24 hrs
exposure, the patches were removed and the resulting reactions evaluated.
The valuation was done again at 72 hrs.
UNEP Publications 65
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (8)
Species : rabbit
Concentration :
Exposure :
Exposure time :
Number of animals :
PDII :
Result : highly irritating
EC classification : irritating
Method : Draize Test
Year : 1977
GLP : no
Test substance : as prescribed by 1.1 - 1.4
Remark : Draize index 5.9 of 8 (reevaluated according to OECD 404)
Source : Roehm,
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (53)
Species : guinea pig
Concentration :
Exposure :
Exposure time :
Number of animals :
PDII :
Result : highly irritating
EC classification : irritating
Method : other: no data
Year : 1997
GLP : no data
Test substance : no data
Remark : Irritation occurs even when using a silicon or 5%Zn cream.
Source : Roehm,
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
09.01.2002 (53)
5.2.2 Eye irritation
Species : rabbit
Concentration : undiluted
Dose : .1 ml
Exposure Time : 2 hour(s)
Comment :
Number of animals : 2
Result : corrosive
EC classification : irritating
Method : other
Year : 1980
GLP : no data
Test substance : as prescribed by 1.1 - 1.4
Remark : Despite the rinsing treatment severe corneal, iris and conjunctival lesions
were displayed by both animals within 2 hrs of instillation. The test was
terminated at this point. It is reasonable to assume that similar levels of
injury would be produced if full scale testing were conducted, and that the
product would be classified as corrosive to the eye.
66 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
Animal No. Time Cornea Iris Conjunctivae
(hrs) Redness Chemosis
5. 2 3 2 3 3
6. 2 4 2 3 4
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : The method described in the Federal Hazardous Substances Labelling Act
Regulations, Section 191.11, published in the Federal Register - 29 F.R.
13009, 1964.
0.1 mL of the test substance was instilled into one eye of each animal. The
lids were gently held togather for one second and the eye was then rinsed
with 20 mL lukewarm water at 4 seconds after instillation. The eyes were
examined 2 hrs after instillation.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (8)
5.3 Sensitization
Type : Guinea pig maximization test
Species : guinea pig
Number of animals : 30
Vehicle : injectable isotonic solution of 0.9% NaCl
Result : not sensitizing
Classification : not sensitizing
Method : OECD Guideline 406 "Skin Sensitization"
Year : 1991
GLP : yes
Test substance : as prescribed by 1.1 - 1.4
Remark : The general behaviour and the body weight gain of the animals were not
influenced by the treatment. After the challenge cutaneous application of
the test substance, a very slight erythema (score 1) was observed on the
right flank of 16 out of 20 treated animals. As the cutaneous reactions were
very slight and the reactions observed at the 24 hrs scoring period were
reversible at the 48 hrs scoring period, the cutaneous reactions were
attributed to orthoergique reaction. No cutaneous reactions lilely to be
caused by the sensitization potential of this test substance (MADAME) were
observed.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : Test animals were 30 Dunkin Hartley guinea pigs (15 males and 15
females) and were allocated to two groups. 10 animals (5 males and 5
females) were in the negative control group and 20 animals (10 males and
10 females) were in the treatment group by MADAME.
Test periods were as follows:
[Induction period] 10 days during this period, the animals were treated with
the vehicle(control group) or the test substance(treated group) as explained
below.
On day 1, 0.1 mL of the test substance was administered by intradermal
route at a concentration of 1 % in an isotonic solition of 0.9 % NaCl.On day
8, 0.5 mL of the test substance at a concentration of 25 % was applied by
cutaneous route.
[Period without treatment] 12 days
[Challange test] 24 hrs
A challenge cutaneous application of 0.5 mL of the vehicle (left flank) and
0.5 mL of the test substance at a concentration of 5 % in the vehicle (right
UNEP Publications 67
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
flank) were performed on all animals. The substances were held in place for
24 hours by means of an occlusive dressing.
[Examination]
The cutaneous reactions were evaluated at the challenge application site,
24 and 48 hrs after removal of the dressing. After the final scoring period,
the animals were sacrificed and cutaneous samples were taken from the
challenge application sites in all animals. Due to the absence of doubtful
macroscopic cutaneous reactions, no histological examination was
performed on the cutameous samples.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (9)
5.4 Repeated dose toxicity
Species : rat
Sex : male/female
Strain : Crj: CD(SD)
Route of admin. : gavage
Exposure period : Males, 43 days
Females, from 14 days before mating to day 3 of lactation (41-52 days)
Frequency of treatment : once daily
Post obs. period : 1 day
Doses : 0(vehicle), 40, 200, 1000 mg/kg/day
Control group : yes, concurrent vehicle
NOAEL : = 200 mg/kg bw
Method : OECD combined study TG422
Year : 1998
GLP : yes
Test substance : other TS: 99.9% purity, Sanyo-Kasei Co.
Result : The NOAELs for repeat dose toxicity are considered to be 200
mg/kg/day for both sexes.
[Males]
At 1000 mg/kg/day, no death was occured.
*By the observation, late onset of twitching, chronic convulsion and
suppression of body weight gain were observed.
*By the histopathological examination:
Degeneration of nerve fibers in the brain and spinal cord, hyperplasia of
the mucosa, edema and inflammatory cell infiltration in the forestomach,and
increased kidneys' weight and livers's weight without histopathological
changes were revealed.
*By the hematological and blood chemical examination:
Slight increse in BUN and slight anemic changes such as decreases in
erythrocyte counts, hemoglobin concentration and hematocrit value,
associated with a significant increase in reticulocyte ratio were revealed.
At 200 mg/kg/day, no adverse effects except for slight anemic changes
such as decrease in hemoglobin concentration and hematocrit value with
increase in reticulocyte ratio were obs erved. However, the severities of this
slight anemic changes were considered toxicologically insignificant.At 40
mg/kg/day, no effects were observed.
[Females]
At 1000 mg/kg/day, 3 females out of 12 died.
*By the observation, late onset of twitching, chronic convulsion,
suppression of body weight gain and a decrease in food consumption in
lactation period were observed.
68 UNEP Publications
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5. TOXICITY Id 2867-47-2
Date 10.01.2002
*By the histopathological examination, the degeneration of nerve fibers in
the brain and the spinal cord, and the hyperplasia of the mucosa in gastric
tract,the edema and inflammatory cell infiltration in the forestomach, and the
atrophy of thethymus were revealed.
Also the increases in the weight of the kidneyand the adrenals
without histopathological changes were observed.
At 200 mg/Kg/day and 40 mg/kg/day, no effects were observed.
Result, cont. The results of the blood examination in male rats are summarized below.
Hematological examination results in male rats
Dose (mg/kg) 0 200 1000
No. of animals 12 12 11
RBC (10000/uL) 881.7 ?43.6 859.8 ?36.7 821.6 ?34.1**
Hematocrit % 46.73 ?2.45 44.84 ?1.26* 41.72 ?1.97**
Hemoglobin 15.91 ?0.69 15.28 ?0.40* 14.24 ?0.74**
g/dL
Reticulocyte 17.81 ?2.61 21.56 ?3.57* 24.84 ?3.75**
Values are expressed as Mean ?S.D.
Significantly different from control: * P<0.05 ** P<0.01
The major histopathological findings in rats are summarized below. Major
histopathological findings in rat.
[Male]
Dose (mg/kg) 0 200 1000
# of animals
12 12 11
Findings in Stomach
Dilatation,
gasteric gland. + 0 0 0
Edema. +0 0 7**
Hyperplasia,
squamous,
forestomach
diffuse. +0 0 11**
Inflammatory cell
infiltration,
forestomach. + 0 0 10**
Ulcer,
forestomach. + 0 0 0
Ulcer,
glandular
stomach +0 0 0
Findngs in
Brain
Degeneration,
nerve fiber + 0 0 3
Spinal cord
Degeneration,
nerve fiber + 0 0 8**
UNEP Publications 69
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Date 10.01.2002
Result, cont. [Female]
Scheduled sacrifice Dead
Dose (mg/kg) 0 200 1000 0 1000
Number of animals 11 12 9 1 a) 3 b)
Findimgs in
Stomach
Dilatation,
gasteric gland. + 0 0 0 0 0/2
Edema. + 0 0 2 0 1/2
Hyperplasia,
squamous,
forestomach
diffuse. + 0 0 9** 0 2/2
Inflammatory cell infiltration,
forestomach. + 0 0 5** 0 1/2
Ulcer,
forestomach. + 0 0 1 0 0/2
Ulcer,
glandular
stomach + 0 0 0 0 1/2
Findngs in
Brain
Degeneration,
nerve fiber + 0 0 4 0 0
Spinal cord
Degeneration,
nerve fiber + 0 0 6** 0 0
Note: + Slight
** Significantly different from control: P< 0.01
a) One animal died of dystocia at 23 of gestation
b) Dead animals were observed at 26 and 38 days after
commencement of administration.
Source : MHW, Japan: 1998
Test condition : Number of animals/group: Males, 12; females, 12
As the LD50 value of > 2000 mg/kg was known, a preliminarytest to decide
the highest dose level at 30, 100, 300, and 1000 mg/kg/day for 14 days was
conducted. At 1000 mg/kg/day, decrease of body weight i n males and
suppression of bodyweight increase in females were observed. Then the
highest dose level for the test was set at 1000 mg/kg/day.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (33)
Species : rat
Sex : male/female
Strain : other: Alderly Park (SPF)
Route of admin. : inhalation
Exposure period : 3 weeks
Frequency of treatment : 6 h/day; 5 d/week
Post obs. period : no
Doses : 15 x 100 ppm or 15 x 250 ppm (Vapour concentration)
Control group : no data specified
NOAEL : = 100 ppm
LOAEL : = 250 ppm
Method : other: not specified
Year : 1970
GLP : no data
70 UNEP Publications
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5. TOXICITY Id 2867-47-2
Date 10.01.2002
Test substance : as prescribed by 1.1 - 1.4
Remark : Strain: Aderly-Park (SPF) 4 males and 4 females in each group. Whole
body exposure. The substance is introduced by a constant-flow pump.
Result : At 250 ppm: Nose and eye irritation, heavy breathing, increase of body
weight is slow. No change of heamtological and clinical parameters. No
pathological (macroscopical and microscopical) effect on organs is
observed.
At 100 ppm: No toxic effect is observed.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Reliability : (2) valid with restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (17)
Species : rabbit
Sex : no data
Strain : no data
Route of admin. : dermal
Exposure period : 7 days
Frequency of treatment : twice per day
Post obs. period : 7 days
Doses : 30 uL on sheared skin (25 % to 35 % in solution)
Control group : yes
Method : other: not specified
Year : 1990
GLP : no data
Test substance : no data
Result : Important morphological change (coagulation, necrosis, oedema and little
cell infiltration of the derm).
Highly irritation due to 2-propenoic acid, 2-methyl,
dimethylaminoethylester is not reversible 7 days after the end of treatment.
Systemic effects were not reported.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.01.2002 (31)
5.5 Genetic toxicity `in vitro`
Type : Bacterial reverse mutation assay
System of testing : Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli
WP2uvr A
Concentration : [Confirmation test for the positive results of the trial tests]
-S9 mix.; 1000,1500,2000, 2500, 3000, 3500, 4000, 4500, 5000
Cycotoxic conc. : More than 3500 ug/plate (TA98, TA1537) without S9 mix in the confirmation
tests
Metabolic activation : with and without
Result : positive
Method : Guidelines for screening mutagenicity testing of chemicals, JAPAN
Year : 1998
GLP : yes
Test substance : other TS: 99.9% purity, Sanyo Kasei Co.
Result The result was positive because the chemical induced mutations more than
two times of the control and the concentration dependency was observed
only in Salmonella typhimurium TA1537 without S9 at 2500 and 3000
ug/plate.
Details of the tests were summarized below.
In the two tests, MADAME caused the revertant colonyincrease of 2 times
UNEP Publications 71
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as much as that of the control to S.typhimurium TA 1537 at 2,500 ug/plate
without S9. But the concentration dependency was not clear.
Also the revertant colony increasing tendency was observed for
S.typhimurium TA98 at 2500 ug/plate and 5000 ug/plate without S9.
The key results are summarized below.
[Results of reverse mutation of MADAME on bacteria]
(without S9)
Items Numbers of revertant colonies
Test per plate
substance [Mean ?S.D]
concentration TA 98 TA 1537
(ug/plate)
Result, cont. : 0 (1st) 17 18 24 776
[20 ?4] [7 ?1]
(2nd) 21 32 26 675
[26 ?6] [6 ?1]
1250 (1st) 19 17 24 768
[20 ?4] [7 ?1]
(2nd) 26 15 27 7 5 11
[23 ?7] [8 ?3]
2500 (1st) 30 44 30 11 15 18
[35 ?8] [15 ?4]
(2nd) 38 38 42 18 14 13
[39 ?2] [15 ?3]
5000 (1st) 19* 46* 37* 4* 3* 6*
[34 ?14] [4 ?2]
(2nd) 33* 54* 27* 1* 4* 2*
[38 ?14] [2 ?2]
Positive
Contro l(1st) 382 384 402 a) 1014 794 1030 b)
[389 ?11] [946 ?132]
(2nd) 413 432 372 b) 946 982 964 b)
[406 ?31] [964 ?18]
*Toxic effect was observed.
a) AF-2 0.1 ug/plate
b) 9-AA: 9-Aminoacridine, 80 ug/plate
Result, cont. (Activation method: +S9)
Items Numbers of revertant
Test colonies per plate.
substance [Mean ?S.D]
concentration TA 98 TA 1537
(ug/plate)
0 (1st) 25 41 40 9 16 10
[35 ?9] [12 ?4]
(2nd) 30 44 36 19 21 18
[37 ?7] [19 ?2]
72 UNEP Publications
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5. TOXICITY Id 2867-47-2
Date 10.01.2002
625 (1st) 39 35 33 13 15 13
[36 ?3] [14 ?1]
(2nd) 39 27 37 14 24 20
[35 ?5] [19 ?5]
1250 (1st) 35 42 48 14 17 13
[42 ?7] [15 ?2]
(2nd) 25 44 34 18 16 14
[34 ?10] [16 ?2]
2500 (1st) 37 32 41 18 20 15
[37 ?5] [18 ?3]
(2nd) 34 46 40 16 16 19
[40 ?6] [17 ?2]
5000 (1st) 52 54 37 20 17 14
[48 ?9] [17 ?3]
(2nd) 38 58 32 24 27 29
[43 ?14] [27 ?3]
Positive
Control (1st) 301 258 265 *85 80 103*
[275 ?23] [89 ?12]
(2nd) 351 375 390* 100 88 82*
[372 ?20] [90 ?9]
* +S9 mix. : 2-Aminoanthracene
Then, to confirm the concentration dependent increase of the revertant
colony at between 2500 to 5000 ug/plate, the confirmation test was
conducted for S. typhimurium TA 1537 and TA 98 by the direct method
without S9.
Result, cont. Toxic effect was observed at 3500 ug/plate and more to TA 98 and TA 1537
without S9 mix. As to TA 1537, the revertant colony increase was observed
by morethan two times of the control at 2500 and 3000 ug/plate. Also the
concentration dependency was observed. As to TA 98, although the
revertant colony increase was observed at 2500 and 3000 ug/plate, it was
less than two times as much as that of the control. The results of TA 1537
satisfied the following 3 conditions to be positive in the reverse mutation.
1) The revertant colony increase should be more than two times of the
control.
2) The revertant colony increase should increase proportionally to the
concentration of the test substance.
(The concentration dependency)
3) The same revertant colony increase should be observed repeatedly by
more than two tests.
4) Then this chemical is considered to be positive in this reverse mutation
test. The number of the induced revertantcolonies/mg was calculated as
3.6/mg. The key results of the confirmation tests are shown below.
The results of the confirmation test are shown below.
(without S9)
Items Numbers of revertant colonies
Test per plate
substance [Means ?S.D]
concentration TA 98 TA 1537
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ug/plate
0 26 23 25 545
[25 ?2] [5 ?1]
1000 25 23 22 88 5
[23 ?2] [7 ?2]
1500 22 23 33 9 11 7
[26 ?6] [9 ?2]
2000 33 36 30 8 79
[33 ?3] [8 ?1]
2500 52 42 39 12 11 16
[44 ?7] [13 ?3]
3000 36 47 42 13 11 21
[42 ?6] [15 ?5]
3500 28* 29* 46* 7* 9* 6*
[34 ?10] [7 ?2]
Result, cont. 4000 17* 22* 16* 5* 4* 3*
[18 ?3] [4 ?1]
4500 15* 7* 10* 3* 3* 4*
[11 ?4] [3 ?1]
5000 10* 15* 17* 3* 8* 4*
[14 ?4] [5 ?3]
Positive
control 343 393 358 a) 933 962 905 b)
[365 ?26] [933 ?29]
* Toxic effect was observed.
a) AF-2; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 0.1 ug/plate
b) 9-AA; 9-Aminoacridine, 80 ug/plate
Source : MHW: Japan, 1998
Test condition : Procedures: Pre-incubation method
Solvent: Distilled water
Positive control:
-S9 mix.: For TA100, TA98, WP2 uvrA;
2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide
For TA-1535: Sodium azide
For TA-1537: 9-Aminoacridine
+S9 mix.: 2-Aminoanthracene (all strains)
S9: Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test : 3
Number of replicates: 2
By the preliminary test to decide the highest concentration, toxicity was
observed at 5000 ug/ plate in the direct method without S9 mix for TA 98
and TA 1537. Then the highest concentration was set at 5000 ug/plate for
all tests.
2 trial tests were done for all cells and a confirmation test was conducted for
TA 98 and TA 1537 which showed positive results in the trial tests.
Test substance : The compositions of the test substance manufactured by Sanyo Kasei Co.
Japan, were as follows: 99.9% MADAME, Impurities:Hydroquinone
74 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
monomethyl ether (as polymerization inhibitor) 2000 ppm, dimethyl amino
ethanol less than 0.1%,methylmethacrylate less than 0.02%.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (33)
Type : Chromosomal aberration test
System of testing : Type of cell used: Chinese hamster lung (CHL/IU) cells
Concentration : [Continuous treatment]
20, 39, 78, 156, 313, and 625 ug/mL.
[Short-term treatment]
200, 400, 600, 800, 1400, and 1600 ug/mL.
Cycotoxic conc. : [Continuous treatment, 24 hrs]
625 ug/mL
[Continuous treatment, 48 hrs]
313 ug/mL
[6 hrs short-term treatment without S9 mix.]
800 ug/mL
[6 hrs short-term treatment with S9 mix.]
1600 ug
Metabolic activation : with and without
Result : Positive
Method : Guidelines for screening mutagenicity testing of chemicals, JAPAN
Year : 1998
GLP : Yes
Test substance : other TS: 99.9% 2-(dimethyl amino)ethyl methacrylate, Sanyo -Kasei Co.
Result This chemical was positive in this test inducing chromosomal aberrations
shown below.
By the 24 hrs and 48 hrs continuous treatment without S9, structural
chromosomal aberrations (including gap) were induced at 625 ug/mL with
88.5% and 76.5% respectively. The numbers of cells with aberration except
gap were 86.5% and 74.0% respectively. The cytotoxicity were observed at
625 ug/mL and 313 ug/mL respectively.
Polyploidy was not induced under these conditions.
By 6 h short-term treatment without S9, concentration-depending structural
chromosomal aberrations (including gap) were induced at 200 ug/mL, 400
mg/mL and 600 ug/mL with 6.5%, 49.5% and 87.5%. The numbers of cells
with aberration except gap were 6.5%, 46.0% and 86.0% respectively.
By 6 h short-term treatment with S9, concentration-depending structural
chromosomal aberrations (including gap) were induced at 800 ug/mL,1400
mg/mL and 1600 ug/mL with 13.5%, 99.5% and 100%. The numbers of
cells with aberration except gap were 13.0%, 99.5% and 100.0%
respectively.
Polyploidy was not induced under these conditions. At more than 800mg/mL
on 6 h short-term treatment without S9 mix and at more than 1600 ug/mL
with S9 mix, cytotoxicity was observed and the metaphase figures were not
observable. As the results, MADAME is considered to induce chromosomal
aberrations. However, the aberrations observed were mainly chromatid
break and chromatid exchange. The data of these tests were summarized in
the tables shown below.
Result, cont. : [Cell growth inhibition test results]
Cell growth inhibition test of CHL cells
continuously treated with 2-(dimethylamino) ethyl methacrylate
without S9 mix.
Concentration Average cell growth rate (%)
ug/mL 24-hour treatment 48-hour treatment
0 (Solvent) 100 100
78 66.0 62.5
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156 61.5 50.0
313 58.0 39.0
625 26.5 20.5
1250 12.0 3.5
2500 10.0 3.0
5000 8.0 2.5
2 cell growth inhibition tests of CHL cells short-term
treatment with 2-(dimethylamino) ethyl methacrylate
with and without S9 mix.
Concentration Average cell growth rate (%)
ug/mL without S9 with S9
0 (Solvent) 100 100
600 56.5 81.0
800 41.5 70.5
1000 28.0 70.5
1200 18.0 70.5
1400 16.5 57.5
1600 11.5 43.5
1800 17.5 33.0
To decide the doses of chromosomal aberrasion test, a preliminarycell
growth inhibition test was conducted. The cell growth ratios were
determined for each doses. The cell growth ratio of the solvent (control) was
defined as 100% and the cell growth ratios of each doses were determined
as the % to the control group. In the case of continuous treatment, over 50
% growth inhibition was observed at 625 ug/mL and greater concentrations
for 24 hours treatment. Therefore the cytotoxic concentration would be
between 313 and 625 ug/mL. As for 48 hrs treatment, 50 % cell growth
inhibition was observed at 156 ug/mL and more than 50 % growth inhibition
was obesrved at 313 ug/mL or greater concentration for 48 hours treatment.
In the case of short treatment, over 50% cell growth inhibition was observed
at 800 ug/mL or greater concentrations without S9 and 1600 ug/mL or
greater concentrations with S9. Then the cytotoxic concentration would be
between 600 and 800 ug/mL without S9 and would be between 1400 and
1600 ug/mL. with S9.
Result, cont.
[Chromosome analysis of Chinesehamster cells (CHL) continuously treated
with MADAME without S9 mix. ]
Table 1-1. Chromosome analysis of Chinese hamster cells (CHL)
continuously treated MADAME without S9 mix.
Time of exposure: 24 hours.
No. of cells analysed: 200 cells
Solvent: Distilled water
- g %: total no. of cells with aberration except gap (%)
+ g %: total no. of cells with aberrations
gap: gap ctd: chromatid break cte: chromatid exchange
csb: chromosome break
cse: chromosome exchange (dicentric and ring) oth: others
tot: total
MNNG: N-methyl-N'-nitro-N-nitrosoguanidine
Concentration
of MADAME
(ug/mL) No. of structural aberrations No. of cells with
aberrations
gap ctd cte csb cse ort tot -g (%) +g (%)
76 UNEP Publications
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5. TOXICITY Id 2867-47-2
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Solvent 0 0 0 0 1 0 1 1 (0.5) 1 (0.5)
20 30 0 0 0 0 3 0 (0) 3 (1.5)
39 00 1 0 1 0 2 2 (1.0) 2 (1.0)
78 01 1 0 0 0 2 1 (0.5) 1 (0.5)
156 00 0 0 1 0 1 1 (0.5) 1 (0.5)
313 01 0 1 2 0 4 4 (2.0) 4 (2.0)
625 22 119 131 42 0 0 314 173 (86.5) 177 (88.5)*
(MNNG)
2.5 11 32 185 7 0 0 235 188 (94.0) 189 (94.5)*
* Significantly different from solvent group data at P<0.01
by Fisher's exact test.
Table 1-2. Chromosome analysis of Chinese hamster cells (CHL)
continuously treated with MADAME without S9 mix.
Time of exposure: 48 hours
No. of cells analysed: 200 cells
Solvent: Distilled water
- g %: total no. of cells with aberration except gap (%)
+ g %: total no. of cells with aberrations
gap: gap ctd: chromatid break cte: chromatid exchange
csb: chromosome break
cse: chromosome exchange (dicentric and ring) oth: others
tot: total.
MNNG: N-methyl-N'-nitro-N-nitrosoguanidine
Result, cont. Concen tration of
MADAME
(ug/mL) No. of structural aberrations No. of cells
with aberrations
gap ctd cte csb cse ort tot -g (%) +g (%)
solvent 1 0 1 0 0 0 2 1 (0.5) 2 (1.0)
20 0 0 0010 1 1 (0.5) 1 (0.5)
39 0 0 0000 1 0 (0 ) 1 (0.5)
78 2 0 0110 4 2 (1.0) 4 (2.0)
156 0 0 0000 0 0 (0 ) 0 (0 )
313 1 0 0020 3 2 (1.0) 3 (1.5)
625 21 61 123 46 0 0 251 148 (74.0) 153 (76.5)*
(MNNG)
2.5 11 39 136 25 17 0 228 159 (79.5) 159 (79.5)*
* Significantly different from solvent group data at P<0.01
by Fisher's exact test.
[Chromosome analysis of Chinese hamster cells (CHL) treated with
MADAME with and without S9 mix.]
Table 2-1 Chromosome analysis of Chinese hamster cells (CHL)
short-term treatment with MADAME without S9 mix.
Time of exposure: 6-(18) hours
No. of cells analysed: 200 cells
Note: At 800,1400 and 1600 ug/mL, no. of cells can't be counted and
analyzed due to toxicity.
Solvent: Distilled water
BP: benzo[a]pyrene
- g %: total no. of cells with aberration except gap (%)
+ g %: total no. of cells with aberrations
gap: gap ctd: chromatid break cte: chromatid exchange
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csb: chromosome break cse: chromosome exchange (dicentric and ring)
oth: others tot: total
Concentration of
MADAME
(ug/mL) No. of structural aberrations No. of cells
with aberrations
Result, cont. gap ctd cte csb cse ort tot -g (%) +g (%)
Solvent 0 0 0 0 1 0 1 1 (0.5) 1 (0.5)
200 1 1 6 0 6 0 14 13 (6.5) 13 (6.5)*
400 18 23 86 6 0 0 133 92 (46) 99 (49.5)*
600 28 115 141 21 0 0 305 172 (86.0) 175 (87.5)*
800 Toxicity
1400 Toxicity
1600 Toxicity
BP
10 11 20004 3 (1.5) 4 (2.0)
* Significantly different from solvent group data at P<0.01
by Fisher's exact test.
Table 2-2 Chromosome analysis of Chinese hamster cells (CHL)
short-term treatment with MADAME with S9 mix.
Time of exposure: 6-(18) hours
No. of cells analysed: 200 cells, At 1600 ug/mL, 84 cells were analyzed.
Solvent: Distilled water
BP: benzo[a]pyrene
- g %: total no. of cells with aberration except gap (%)
+ g %: total no. of cells with aberrations
gap: gap ctd: chromatid break cte: chromatid exchange
csb: chromosome break
cse: chromosome exchange (dicentric and ring) oth: others
tot : total
Concentration of
MADAME
(ug/mL) No. of structural aberrations No. of cells
with aberrations
gap ctd cte csb cse ort tot -g (%) +g (%)
Solvent 0 0 1000 1 1 (0.5) 1 (0.5)
200 0 0 00 20 2 2 (1.0) 2 (1.0)
400 0 0 00 00 0 0 (0) 0 (0)
600 1 1 30 20 7 6 (3.0) 7 (3.5)
800 2 2 24 0 2 0 30 26 (13.0) 27 (13.5)*
1400 13 146 194 45 0 0 398 199 (99.5) 199 (99.5)*
1600 6 60 81 21 0 0 168 84 (100) 84 (100)*
BP
10 9 11 112 1 2 0 138 116 (58.0) 117 (58.5)*
* Significantly different from solvent group data at P<0.01
by fisher's exact test.
Source : MHW: Japan, 1998
Test condition : Solvent: Distilled water
Positive control: -S9 mix, N-Methyl-N'-nitro-N-nitrosoguanidine
+S9 mix, Benzo[a]pyrene
Doses: -S9 mix. (24 and 48-hr continuous treatment) : 0, 20,
39, 78 156, 313, 625 ug/mL
-S9 mix. (6-hr short-term treatment) : 0, 200, 400,
600, 800, 1400, 1600 ug/mL
78 UNEP Publications
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+S9 mix. (6-hr short-term treatment): 0, 200, 400,
600,800, 1400, 1600 ug/mL
S9: Rat liver, induced with phenobarbital and
5,6-benzoflavone
Plate/test: 2
By the preliminary cytostatic test to know the cytotoxicity doses, following
cytotoxicity doses were revealed.
[Continuous treatment, 24 hrs] 625 ug/mL
[Continuous treatment, 48 hrs] 313 ug/mL
[6 hrs short-term treatment without S9 mix.] 800 ug/mL
[6 hrs short-term treatment with S9 mix.] 1600 ug/mL
Based on these data, above shown doses were decided for these tests.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (33)
Type : Cytogenetic assay
System of testing : Human lymphocytes
Concentration : 0, 66.39, 88.52, 118.0, 157.4, 209.8, 279.8, 373, 497.4, 663.2, 884.3, 1179,
1572 ug/Ml
Cycotoxic conc. :
Metabolic activation : with and without
Result : positive .
Method : other
Year : 1991
GLP : Yes
Test substance : as prescribed by 1.1 - 1.4
Remark The cells sampled at 20 hours after the start of treatment, were analysed for
the chromosomal aberrations. At the higher two concentrations, namely
1179 ug/mL without S9 and 1572 ug/mL with S9, this chemical induced the
aberrations which were significantly different from those observed in the
concurrent solvent controls. No exchange-type aberrations were observed,
but only the deletion-type aberrations were seen. The numbers of cells with
aberration including gap (average of two tests) at 1179 ug/mL without S9
and 1572 ug/mL with S9 were 19.5% and 12.5% respectively.The numbers
of cells with aberration exccluding gap (average of two tests) at 1179 ug/mL
without S9 and 1572 ug/mL with S9 were 11.0% and 7.5% respectively. No
marked mitomic inhibition was evident in any of the doses analysed in this
study.
The mitomic index at 1179ug/mL without S9 and 1572 ug/mL with S9
(average of two tests) were 2.3% and 6.2 % respectively. It is concluded
that MADAME may induce the chromosomal aberrations in the human
peripheral blood lymphocytes.
ABERRATIONS OBSERVED
[Without S9]
Items Solvent 884.3 1179 50
ug/mL ug/mL ug/mL (MMS)
A B A+B A B A+B A B A+B A B A+B
Culture
Cells
scored: 100 100 200 100 100 200 100 100 200 25 25 50
Gaps 3 36 3 6 9 11 6 17 32 5
Chr. del. 0 11 1 0 1 1 34 527
Chr. exch 0 00 00 0 0 0 0 0 00
Ctd. del. 0 00 8 5 13 11 7 18 4 5 9
Ctd. exch 0 00 00 0 0 0 0 347
Other. 00 0 00 0 0 0 0 0 00
UNEP Publications 79
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5. TOXICITY Id 2867-47-2
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Summary of aberrations observed
MITOTIC INDEX (%)
TREATMENT
(UG/ML) 20 HOURS
-S 9 +S9
A B A B
SOLVENT 5.6 6.0 6.3 6.8
66.39 NM NM NM NM
88.52 NM NM NM NM
118.0 NM NM NM NM
157.4 NM NM NM NM
209.8 NM NM NM NM
279.8 NM NM NM NM
373.0 6.2 4.8 NM NM
497.4 6.0 4.3 7.2 4.6
663.2 4.8 4.9 6.0 5.2
884.3 4.3 3.9 6.8 6.5
1179.0 2.3 2.2 6.4 5.3
1572.0 0 0 6.2 6.2
NM: NOT MADE
Remark, cont. : Total
incl gaps 3 4 7 12 11 23 23 16 39 15 13 28
(%) (3.5) (11.5) (19.5) (14.0)
excl gaps 0 1 1 9 5 14 12 10 22 12 11 23
(%) (0.5) (7.0) (11.0) (11.5)
[With S9]
Items Solvent 1179 1572 25
ug/mL ug/mL ug/mL (CPA)
A B A+B A B A+B A B A+B A B A+B
Culture
Cells
scored: 100 100 200 100 100 200 100 100 200 25 25 50
Gaps 2 35 437 7 3 10 538
Chr. del. 0 1 1 2 02 22 4 112
Chr. exch 0 0 0 011 00 0 000
Ctd. del. 1 0 1 1 34 5 6 11 14 10 24
Ctd exch 0 0 0 0 00 000 112
Other 0 00 0 00 000 000
Total
incl gaps 3 4 7 7 7 14 14 11 25 21 15 36
(%) (3.5) (7.0) (12.5) (18.0)
excl gaps. 1 1 2 347 7 8 15 16 12 28
(%) (1.0) (3.5) (7.5) (14.0)
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (4)
Type : HGPRT assay
System of testing : V79 Chinese Hamster Cells
80 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
Concentration : with S9 mix : 62.5 - 125 - 250 - 500 - 1000 - 1500 - 2000 ug/m L ;
without S9 mix : 31.25 - 62.5 - 125 - 250 - 500 ug/mL
Cycotoxic conc. : > 1000 ug/mL
Metabolic activation : with and without
Result : Negative
Method : OECD Guideline 476 "Genetic Toxicology: In vitro Mammalian Cell Gene
Mutation Tests"
Year : 1992
GLP : Yes
Test substance : as prescribed by 1.1 - 1.4
Remark : Although round and refringent cells were observed at 250 ug/mL, the
mutation frequency in the cells from duplicate cultures treated with
MADAME was considered as similar to that of the negative and solvent
controls, with and without S9: i.e. no significant increase (3 fold increase
over the controls) was observed. MADAMe did not show mutagenic activity
in this HPRT gene mutation aasay in V 79 Chinese hamster cells.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : Metabolic activation: S9 mix microsomal rat liver portion and cofactor.
By the preliminary cytotoxicity test, the cytotoxicity (decrease in the cloning
efficiency and/or dead cells) was shown at the concentrations of equal or
greater than 1000 ug/mL, both with or without S9 mix. At 250 ug/mL or
higher, round and refringent cells were observed.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (5)
Type : Salmonella typhimurium reverse mutation assay
System of testing : Strains TA1535, TA 1537, TA 1538, TA 98, TA 100
Concentration : 100 - 500 - 1000 - 2500 and 5000 ug/plate
Cycotoxic conc. : slight toxicity at 5000 ug/plate for TA 100
Metabolic activation : with and without
Result : Negative
Method : OECD Guideline 471 "Genetic Toxicology: Salmonella thyphimurium
Reverse Mutation Assay"
Year : 1991
GLP : Yes
Test substance : as prescribed by 1.1 - 1.4
Remark : The test substance, MADAME, did not induce a significant increase in the
revertant number with or without S9 mix in any of 5 strains.
The negative and solvent control results were equivalent to those usually
obtained in this Laboratory. The number of revertants induced by the
positive control was higher than the spontaneous one, which
demonstrateted the sensitivity of this test and the efficacy of the S9 mix
throughout this study.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : Metabolic activation : S9 mix microsomal rat liver portion and cofactor
-S9 mix.: Sodium azide(NaN3 ) for TA 1535 and TA 100
9-amino-acridine (9AA) for TA 1537
2-nitrofluorene (2NF) for TA 1538 and TA 98
+S9 mix.: 2-anthramine (2AM) for all strains
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (3)
UNEP Publications 81
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
5.6 Genetic toxicity `in vivo`
Type : Micronucleus assay
Species : mouse
Sex : male/female
Strain : NMRI
Route of admin. : gavage
Exposure period : one dose
Doses : 1000 mg/kg (maximum tolerated dose)
Result : negative
Method : OECD Guideline 474 "Genetic Toxicology: Micronucleus Test"
Year : 1989
GLP : yes
Test substance : as prescribed by 1.1 - 1.4
Remark : In comparison with the corresponding negative controls there was no
substantial enhancement in the frequency of the detected micronuclei at
any preparation interval after application of the test article. The mean values
of micronuclei observed after treatment with MADAME were in the same
range compared to the negative control groups. In the positive control group
a distinct increase of induced micronuclei frequency was observed.In
conclusion, the test article did not induce micronuclei as determined by the
micronucleus test in the bone marrow cells of the mouse.
[Summary of the test results]
Sampling time: 24 hrs
Group Dose PCEs with Micronuclei in PCE/NCE
--------- mg/kg bw Micronuclei 1000 PCE (mean)
(%) (Range)
Solvent 0 0.06 0? 1000 / 554
Test article 1000 0.03 0?2 1000 / 653
CPA 40 0.75 1 ?13 1000 / 742
Sampling time: 48 hrs
Group Dose PCEs with Micronuclei in PCE/NCE
--------- mg/kg bw Micronuclei 1000 PCE (mean)
(%) (Range)
Solvent 0 0.04 0?2 1000 / 680
Test article 1000 0.04 0?1 1000 / 744
Remark, cont. : Sampling time: 72 hrs
Group Dose PCEs with Micronuclei in PCE/NCE
--------- mg/kg bw Micronuclei 1000 PCE (mean)
(%) (Range)
Solvent 0 0.06 0? 1000 / 594
Test article 1000 0.09 0? 1000 / 506
CPA : cyclophosphamide
PCE : polychromatic erythrocytes
NCE : normochromatic erythrocytes
Source : Roehm,
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Test condition : Group: 5 males and 5 females
Negative control: distilled water
Positive control: Cyclophosphamid in physiological serum (NaCl)
82 UNEP Publications
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5. TOXICITY Id 2867-47-2
Date 10.01.2002
Dose: 40 mg/kg
Bone marrow preparation: 24, 48 and 72 hrs after application.
Analysis : 1000 PCE (Polychromatic Erythrocytes) per animal
By a preliminary test, 1000 mg/kg b.w. was estimated to be the maximum
tolerated dose. The animals expressed toxic reactions. After treatment with
the test article the ratio between PCEs and NCEs was not affected as
compared to the corresponding negative controls, thus indicating no
cytoyoxic effects.
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (52)
Type : Micronucleus assay
Species : mouse
Sex : male/female
Strain : Swiss OF1/ICO:OF1 IFFA-CREDO
Route of admin. : i.p.
Exposure period : 2 administrations separated by 24 hrs
Doses : 200 mg/kg
Result : negative
Method : OECD Guideline 474 "Genetic Toxicology: Micronucleus Test"
Year : 1993
GLP : yes
Test substance : as prescribed by 1.1 - 1.4
Remark : Group: 5 males and 5 females
2 administrations by 24 hrs via intraperitoneal route. 200 mg/kg MADAME
in 10 mL isotonic solution 0.9% NaCl was administratedd to mouse.
Positive control: Cyclophosphamide
Dose: 25 mg/kg (2 ip injectons)
Bone marrow preparation 24 h and 48 h after the 2nd administration.
Analysis : the presence of micronuclei in 2000 polychromatic
erythrocytes per mouse and the ratio of PCE/NCE.
Result : In all groups treated with MADAME, the mean values of micronucleated
polychromatic erythrocytes were similar to those of their respective vehicle
groups at each sampling time, and no statiscally significant differences were
observed. The PE/NE ratio did not differ from that of the respective vehicle
control group.
MADAME did not induce cytogenetic damage to the bone marrow cells of
mice when treated twice separated by 24 hrs by intraperioneal route at 200
mg/kg in the micronucleus test.
[Summary of the test results]
Time of sacrifice: 24 hrs after the 2 nd administration
Group doses MPE/PE PE/NE ratio
--------- (mg/kg) Mean (SD) Mean (SD)
vehicle ----- 2.0 (0.8) 0.7 (0.2)
Test substance 200 1.9 (1.1) 0.6 (0.2)
CPA 25 18.2 (3.8)# 0.4# (0.1)
Time of sacrifice: 48 hrs after the 2 nd administration
Group doses MPE/PE PE/NE ratio
--------- (mg/kg) Mean (SD) Mean (SD)
vehicle ----- 1.9 (0.8) 0.9 (0.4)
Test substance 200 1.7 (1.0) 1.2 (0.6)
10 animals (5 males, 5 females) per group
UNEP Publications 83
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5. TOXICITY Id 2867-47-2
Date 10.01.2002
# : P < 0.001
Vehicle: physiological solution
CPA : cyclophosphamide
PE : polychromatic erythrocytes
NE : normochromatic erythrocytes
MPE/PE: micronucleated polychromatic erythrocytes/1000
Polychromatic erythrocytes.
(SD) : standard deviation.
Source : Atochem Paris la Defense, 1993
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
09.01.2002 (7)
5.7 Carcinogenity
5.8 Toxicity to reproduction
Type : other
Species : rat
Sex : male/female
Strain : Crj: CD(SD)
Route of admin. : gavage
Exposure period : Males, 14 days before mating Females, from 14 days before mating to day
3 of lactation
Frequency of treatment : Once daily
Premating exposure
period.
Male : 14 days
Female : 14 days
Duration of test : 41-52 days
Doses : 0(Vehicle), 40, 200, 1000 mg/kg/day
Control group : yes, concurrent vehicle
NOAEL Parental : = 200 mg/kg bw
Method : OECD combined repeated dose and reproductive/developmental toxicity
screening test
Year : 1998
GLP : yes
Test substance : other TS: 99.9% purity, Sanyo-Kasei Co., Japan
Remark As the LD50 value of > 2000 mg/kg was known, a preliminarytest to decide
the highest dose level at 30, 100, 300 and 1000 mg/kg/day for 14 days was
conducted. At 1000 mg/kg/day, decrease of body weight in males and
suppression of bodyweight increase in females were observed. Then the
highest dose level for the test was set at 1000 mg/kg/day.
Result : NOAELs = 1000 mg/kg/day for males
= 200 mg/kg/day for females
= 200 mg/kg/day for offsprings
The compound had no effects on reproductive parameteres such as the
mating index, the fertility index, numbers of corpora lutea or implantations,
the implantation index, the delivery index, the gestation index, gestation
length or parturition. Three dams of the 1000mg/kg group, however, lost all
their pups in the lactation period. As reported in 5.4 repeated dose toxicity,
significant adverse effects were observed in animals of 1000 mg/kg/day
group, especially in females. These adverse effects observed in females
84 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
5. TOXICITY Id 2867-47-2
Date 10.01.2002
were as follows:
* 3 females out of 12 died.
* By the observation, late onset of twitching, chronic convulsion,
suppression of body weight gain and a decrease in food consumption in
lactation period were observed.
* By the histopathological examination, the degeneration of nerve fibers in
the brain and the spinal cord, and the hyperplasia of the mucosa in
gastric tract,the edema and inflammatory cell infiltration in the
forestomach, and the atrophy of thethymus were revealed.
Also the increases in the weight of the kidneyand the adrenals without
histopathological changes were observed.
On examination of neonates, the 1000 mg/kg dosewas associated with a
decrease in body weight and a low viability index.
There were no significant differences in number of offspring or live offspring,
the sex ratio or the live birth index. No abnormalities ascribable to the
compound were found for external features, clinical signs or necropsy
findings for the offspring. The key data are summarized in the table shown
below.
Result, cont. :
[Reproductive parameters]
Dose 0 40 200 1000
(mg/kg)
Number of 12 12 12 10
pairs examined
Numbers 12 12 11 10
of pairs with
successful mating
Mating 100.0 100.0 91.7 100.0
index (%)
Number of 12 12 11 9
pregnant females
Fertility 100.0 100.0 100.0 90.0
index (%)
Pairing 2.5 ? 3.1 ? 3.9 ? 2.8 ?br>
days 1.0 1.0 3.0 1.0
until mating
Number of 0.0 ? 0.0 ? 0.1 ? 0.0 ?br>
estrous 0.0 0.0 0.3 0.0
stages without
mating*
Mating index (%) = (No. of pairs with successful mating /No. of pairs
examined)x100
Fertility index (%) = (No. of pregnant animals / No. ofpairs with successful
mating) x 100
* Values are expressed as Mean ?S.D.
[developmental parameters]
Dose 0 40 200 1000
(mg/kg)
Number of 12 12 11 8
females
examined
Live birth 98.03 ?100.00 ? 93.18 ?89.06 ?br>
UNEP Publications 85
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5. TOXICITY Id 2867-47-2
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index* (%) 4.52 0.00 22.61 12.64
Numbers 14.3 ? 15.5 ? 13.1 ?11.0 ?br>
of live 1.6 1.2 5.1 3.7
pups
on day 0
Nummbers 14.0 ? 15.5 ? 14.0 ? 7.8 ?br>
of live 1.5 1.2 3.7 4.2
pups
on day 4*
Body weight of pups (g)
Result, cont. On day 0
Male* 7.2 ?0.4 6.6 ?0.4 6.9 ?0.7 6.4 ?1.1**
Female* 6.8 ?0.6 6.3 ?0.5 6.5 ?0.7 6.0 ?0.9**
On day 4
Male* 11.1 ?1.1 10.4 ?0.9 10.8 ?2.0 10.2 ?2.5
Female* 10.7 ?1.3 9.8 ?1.0 10.4 ?2.0 9.8 ?1.8
*: Value are expressed as Mean ?S.D.
**: Significantly different from control ; p<0.05.
Source : MHW: Japan, 1998
Reliability : (1) valid without restriction
Flag : Critical study for SIDS endpoint
10.01.2002 (33)
5.9 Developmental toxicity/teratogenicity
5.10 Other relevant information
Type : Cytotoxicity
Remark : Result : Cell growth inhibition in Balb/c 3T3 Fibroblasts.
ID50 > 100 umol/l (endpoints observed : inhibition of DNA
synthesis, protein synthesis, total protein content, irriversible inhibition of
cell metabolism.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (19)
Type : Metabolism
Remark : Result : The subtance was rapidly hydrolysed to methacrylic acid and N,N,-
dimethylaminoethanol when incubated with simulated saliva or simulated
intestinal fluid in vitro. 90 % degradation was observed in simulated saliva
after 4 hours at 37癈, 86 % degradation after incubation with simulated
intestinal fluid for 4 hours at 37癈. Degradation was below 8 % after
incubation with simulated gastric fluid for 4 hours at 37癈.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (6)
Type : Metabolism
Remark : Small quantities of mathacrylates may readily be metabolized by
86 UNEP Publications
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5. TOXICITY Id 2867-47-2
Date 10.01.2002
saponification into the alcohol and methacrylic acid. The latter may form
acetyl-CoA derivatives, which then enters the normal lipid metabolism.
Source : Clayton/Patty
10.01.2002 (13)
Type : other
Remark : 1) Anesthetized dogs following intraveneous administration
of 2.4, 4.7, 9.7, 18.9 mg/kg
* Increase the respiratory rate
* Decrease the heart rate
* Hypertension blood, Effect up to 30-40 mn
2) Effects on isolated rabbit heart following perfuse with
solutions 1/1000, 1/10000, 1/100000 (v/v)
* Decrease in the heart rate, force of
contraction and coronary flow
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (34)(35)
Type : other
Remark : Effects on smooth muscles were stu died on guineapig isolated ileum.
3 concentrations: 1/25000; 1/50000; 1/100000.
At 1/100000, Increase of contractility.
Atropin (0.1 mug/ml) dit not antagonise the effects.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (34)
Type : other
Remark : Route of administration: i.v.
Species: Rat with sarcoms 45 or mammary carcinomas
Result: Decrease of neoplastic, dystrophic and necrotic changes of
tumours.
No data on doses and duration of injections
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (29)
Type : other
Remark : Species: rabbit
Route of Administration: gavage
Result: Decrease of electrical and cerebral activity and clonico-tonic
convulsions. Chronic studies in rats and rabbits with 0.1 x LD16 did not
affect growth, blood parameters, electrolytic equilibrium, weight of organs
and renal and hepatic functions.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
18.05.1994 (36)
Type : other: Enzyme inhibition in vitro
Remark : Result : The substance did not inhibit cholinesterase activity of the isolated
enzyme or in rat brain preparations in vitro.
Source : Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)
10.12.2001 (55)
5.11 Experience with human exposure
UNEP Publications 87
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
6. REFERENCES Id 2867-47-2
Date 10.01.2002
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(22) IGNAT'EVA, F.K. et al, 1976.Hydrolysis of aminoalkyl esters of methacrylic acid in
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(23) Izmerov, N.F. et al., Toxicometric Parameters of Industrial Toxic Chemical Under Single
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88 UNEP Publications
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
6. REFERENCES Id 2867-47-2
Date 10.01.2002
(25) Kirk-Othmer Encyclopedia of Chemial Technology 4th ed. New York, NY: John Wiley and
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(29) Kvakina E.B. et al., Vopr. Klin. Onkol. Neiroendokrinnykh Narushenii Zlokach. Novoobraz.,
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(30) LAWRENCE, W.H. et al (1972) J. Dental. Research, 51(2), 526-535
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(34) Mir G.N. et al., J. Pharmac. Sci., 62, 778-782 & 1258-1261, 1973
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UNEP Publications 89
OECD SIDS 2-DIMETHYLAMINOETHYLMETHACRYLATE
6. REFERENCES Id 2867-47-2
Date 10.01.2002
(49) Roehm GmbH, cofidential information given to Beratergremium umweltrelevante Altstoffe
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90 UNEP Publications
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7. SUMMARY & EVALUATION Id 2867-47-2
Date 10.01.2002
7.1 End point summary
7.2 Hazard summary
7.3 Risk assessment
UNEP Publications 91
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