Triethylene Glycol Dibenzoate
File No: NA/817
31 October 2000
NATIONAL INDUSTRIAL CHEMICALS NOTIFICATION
AND ASSESSMENT SCHEME
FULL PUBLIC REPORT
Triethylene Glycol Dibenzoate
This Assessment has been compiled in accordance with the provisions of the Industrial Chemicals
(Notification and Assessment) Act 1989 (the Act) and Regulations. This legislation is an Act of the
Commonwealth of Australia. The National Industrial Chemicals Notification and Assessment
Scheme (NICNAS) is administered by the National Occupational Health and Safety Commission
which also conducts the occupational health & safety assessment. The assessment of environmental
hazard is conducted by the Department of the Environment and the assessment of public health is
conducted by the Department of Health and Aged Care.
For the purposes of subsection 78(1) of the Act, copies of this full public report may be inspected by
the public at the Library, National Occupational Health and Safety Commission, 92-94 Parramatta
Road, Camperdown NSW 2050, between the following hours:
Monday - Wednesday 8.30 am - 5.00 pm
Thursday 8.30 am - 8.00 pm
Friday 8.30 am - 5.00 pm
Copies of this full public report may also be requested, free of charge, by contacting the
Administration Coordinator on the fax number below.
For enquiries please contact the Administration Coordinator at:
Street Address: 92 -94 Parramatta Rd CAMPERDOWN NSW 2050, AUSTRALIA
Postal Address: GPO Box 58, SYDNEY NSW 2001, AUSTRALIA
Telephone: (61) (02) 9577 9514 FAX (61) (02) 9577 9465
Director
Chemicals Notification and Assessment
TABLE OF CONTENTS
FULL PUBLIC REPORT ...................................................................................................................... 3
1. APPLICANT .............................................................................................................................. 3
2. IDENTITY OF THE CHEMICAL.............................................................................................3
?Comments on Chemical Identity ................................................................................................ 4
3. PHYSICAL AND CHEMICAL PROPERTIES ........................................................................ 4
4. PURITY OF THE CHEMICAL.................................................................................................7
5. USE, VOLUME AND FORMULATION ................................................................................. 8
6. OCCUPATIONAL EXPOSURE...............................................................................................8
7. PUBLIC EXPOSURE................................................................................................................9
8. ENVIRONMENTAL EXPOSURE ......................................................................................... 10
Release ......................................................................................................................................... 10
Fate ............................................................................................................................................... 10
9. EVALUATION OF TOXICOLOGICAL DATA .................................................................... 12
9.1 Acute Toxicity..................................................................................................................12
9.1.1 Oral Toxicity (McRae, 1998b).....................................................................................13
9.1.2 Dermal Toxicity (McRae, 1998a) ................................................................................ 13
9.1.3 Inhalation Toxicity.......................................................................................................14
9.1.4 Skin Irritation (Parcell, 1998b) .................................................................................... 14
9.1.5 Eye Irritation (Parcell, 1998a)......................................................................................15
9.1.6 Skin Sensitisation (Coleman, 1998).............................................................................15
9.2 Repeated Dose Toxicity (Paffett, 1999)...........................................................................18
9.3 Genotoxicity..................................................................................................................... 19
9.3.1 Salmonella typhimurium and Escherichia coli Reverse Mutation Assay (Kitching,
1998) 19
9.3.2 Chromosomal Aberration Assay in Human Lymphocytes (Akhurst, 1998) ................ 20
9.3.3 Mammalian Cell Gene Mutation Test in vitro in the Mouse (Adams, 1998) .............. 22
9.4.1 Estrogenic Activity Study (Reel, 1997) ....................................................................... 23
9.5 Overall Assessment of Toxicological Data......................................................................26
10. ASSESSMENT OF ENVIRONMENTAL EFFECTS.........................................................26
11. ASSESSMENT OF ENVIRONMENTAL HAZARD.........................................................27
12. ASSESSMENT OF PUBLIC AND OCCUPATIONAL HEALTH AND SAFETY
EFFECTS ......................................................................................................................................... 28
13. RECOMMENDATIONS ..................................................................................................... 29
14. MATERIAL SAFETY DATA SHEET ............................................................................... 30
15. REQUIREMENTS FOR SECONDARY NOTIFICATION................................................30
16. REFERENCES .................................................................................................................... 30
MSDS................................................................................................................................................... 34
NA/817
FULL PUBLIC REPORT
Triethylene Glycol Dibenzoate
1. APPLICANT
Velsicol Australia Limited of 10 William Street TURRAMURRA NSW 2074 has submitted a
standard notification statement in support of their application for an assessment certificate for
`Triethylene Glycol Dibenzoate'.
2. IDENTITY OF THE CHEMICAL
The notifier did not apply for any information relating to `Triethylene Glycol Dibenzoate' to
be exempt from publication in the Full Public Report and Summary Report.
Triethylene glycol dibenzoate.
Chemical Name:
Chemical Abstracts Service
120-56-9
(CAS) Registry No.:
Benzoflex S-358;
Other Names:
Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, dibenzoate;
Ethylenbis(oxyethylene)dibenzoate.
Benzoflex 2088 (product containing 25% Benzoflex S-
Marketing Name:
358).
C20H22O6
Molecular Formula:
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Structural Formula:
H2
H2 H2
O
O C
C C C
O
O
C
C C O C O
H2
H2 H2
358.39
Molecular Weight:
Method of Detection and
UV, IR, NMR and GC
Determination:
Spectra of UV, IR and NMR were provided. The
Spectral Data:
characteristic absorbances serve to identify and
characterise the new chemical.
?Comments on Chemical Identity
The new chemical is the di-ester of triethylene glycol with benzoic acid, although the
commercial product contains around 1.3% of the mono-ester and a small percentage of
dipropylene glycol esters.
3. PHYSICAL AND CHEMICAL PROPERTIES
White to off-white solid with a mild ester odour.
Appearance at 20癈 & 101.3 kPa:
43.5-49.0癈 (see comments below).
Melting Point:
Boiling Point: Not determined; decomposes above 230癈 without
boiling.
1.256
Specific Gravity:
2.5x10-8kPa at 25癈 (see comments below).
Vapour Pressure:
2.83x10-4 Pa.m3/mol (see comments below).
Henry's law Constant:
30.4 mg/L (see comments below).
Water Solubility:
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Partition Co-efficient
Log POW=3.2 (see comments below).
(n-octanol/water):
T1/2 at pH 9 = 4.9 days (calculated);
Hydrolysis as a Function of pH:
T1/2 at pH 8 = 49 days (calculated);
T1/2 at pH 7 = 1.3 years (calculated);
(see comments below).
Log KOC=3.2 (see comments below).
Adsorption/Desorption:
Not determined (see comments below).
Dissociation Constant:
151癈
Flash Point:
Non-pyrophoric.
Flammability Limits:
None below 400癈.
Autoignition Temperature:
Not explosive.
Explosive Properties:
Non-oxidising.
Reactivity/Stability:
Comments on Physico-Chemical Properties
The physico-chemical properties of the compound were determined using OECD test
protocols.
The melting point range was determined using the capillary tube method. The 5.5 oC range of
melting temperatures is in accordance with the presence of congeners of the notified chemical
in the test material. The boiling point could not be determined since the test substance
decomposed without boiling at temperatures above 230 oC.
The vapour pressure (VP) was determined using a balance system where the VP was
determined at a number of temperatures between ambient and 250 oC using a mass difference
technique. The data were then fitted to a linear relation relating LogVP to reciprocal
temperature (degrees K), and this relationship used to calculate the VP at 25 oC. The
relationship derived from the data was:
Log VP (Pa) = -3729.81/T(oK) + 7.895
A lowVP for a compound of this nature with high molecular weight is expected, but it should
be noted that since the material contains an appreciable amount of lower molecular weight
impurities (eg. triethylene glycol monobenzoate) which are likely to be more volatile, the
measured VP may be appreciably higher than that of the pure notified chemical.
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The water solubility was determined in triplicate using the shake flask method.
Approximately 2 g of the test material was weighed into five separate flasks, then shaken with
100 mL of pH 7.0 buffer (H2PO4-/OH-) at 30 oC for 1, 2, 3, 4 and 5 days. Following this
period of agitation the flask was allowed to stand for at least 24 hours at 20 oC, and the
resulting solutions were filtered and analysed for the dissolved material. Each aqueous
solution was extracted three times with ethyl acetate, the combined extracts evaporated to
dryness, the resulting residue taken up in acetone, and the acetone solutions then analysed (in
duplicate) for the test compound using gas chromatography. The resultant concentrations of
triethylene glycol dibenzoate in the aqueous phase were determined as 19.0, 22.2, 29.7, 31.8
and 29.7 mg/L for the agitation periods of 1, 2, 3, 4 and 5 days respectively. The mean for the
last three days is 30.4?.1 mg/L, and this was taken as the solubility of triethylene glycol
dibenzoate in water. It should be noted that the gas chromatogram also detected impurities in
the aqueous extract, and the test report noted that the triethylene glycol monobenzoate is
appreciably more water soluble than the dibenzoate.
The Henry's Law Constant at 20 oC was calculated from the measured VP and water
solubility at this temperature (see above) using the formula:
H = Vapour pressure x MW/Water solubility.
Hydrolytic degradation and fat solubility of the compound were not determined
experimentally. However, in respect of hydrolytic degradation, although the ester
functionalities may be susceptible to hydrolytic cleavage under extremes of pH, hydrolysis is
unlikely in the environmental pH range between 4 and 9.
The n-octanol/water partition coefficient was determined in triplicate using the HPLC
method, where the retention time of the test compound on C18 columns was compared with
those for seven reference compounds of known Pow. The reference compounds ranged from
ethyl benzoate (Log Pow = 2.6) to triphenylamine (Log Pow = 5.7). The retention times of
the major component of the new material indicated a Log Pow of 3.2 for all three samples
tested. The report also included an estimate of Log Pow of 2.77 based on Quantitative
Structure Activity Relationships (QSAR).
Log Pow values of this magnitude indicate that the compound has a moderately high affinity
for the oil phase, a property expected for compounds with high aliphatic and aromatic
hydrocarbon content.
The value for Log Koc, a measure of the compound's ability to bind to the organic component
of soils and sediments, was also determined using comparison of retention times on a C18
HPLC column. Six standard compounds were employed ranging from phenol with Log Koc
= 1.43, to 4, 4'-DDT with Log Koc = 5.38. The retention time of the new compound was
intermediate between the values of these two end sequence reference compounds, and
provided the value for Log Koc of 3.2. This high value for Log Koc indicates that the
chemical will bind strongly to the organic component of soils and sediments, although some
mobility in these media may be possible.
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The new compound contains no acidic or basic groups, so dissociation constant data are not
relevant.
The ASTER data base of the US EPA is a source of physico-chemical information derived
from QSARs, and it is of interest to compare this derived data with the measured parameters
discussed above. For the present compound (USEPA, 2000) the relevant derived data are
tabulated below.
Data From ASTER Data Base of US EPA.
1.2 X 10-7 Pa at 25 oC.
VP:
30.8 mg/L at 20 oC
Water Solubility:
1.38 X 10-6 Pa/mol m3
Henry's Law Constant:
Hydrolysis: Half life = 400 days.
Partition Co-efficient: Log Pow = 3.95
Adsorption/Desorption: Log Koc =3.48
The calculated water solubility is in excellent agreement with the measured value, and the
estimated values for Log Pow and Log Koc are also in reasonable accord with experimental
data. However, the QSAR estimates of VP (and consequently the Henrys Law Constant) are
two orders of magnitude lower than the experimental values. This discrepancy is due to the
presence of lower molecular weight impurities in the commercial product, and consequently
the ASTER data is to be preferred when using VP for estimating the environmental fate of the
chemical.
4. PURITY OF THE CHEMICAL
96.9%
Degree of Purity:
None
Hazardous Impurities:
Non-hazardous Impurities
(> 1% by weight):
Chemical name: Triethylene glycol monobenzoate
Weight percentage: 1.26
CAS No.: 25022-51-7
Chemical name: Dipropylene glycol dibenzoate
Synonyms: Propanol, oxybis-, dibenzoate
Weight percentage: 1.5
CAS No.: 27138-31-4
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None
Additives/Adjuvants:
5. USE, VOLUME AND FORMULATION
The notified chemical, Benzoflex S-358, is a plasticiser in adhesive formulations. It will be
imported as a component (25%) in a product named Benzoflex 2088. Benzoflex 2088 can be
used in a variety of adhesive applications, such as consumer white glue, carpenter glue,
packaging adhesives, wood glue, book binding or forms.
Benzoflex 2088 will be shipped in (US) 55 gallon drums or 205 L Intermediate Bulk
Containers (IBC). The import volume for the notified chemical, Benzoflex S-358, is 25 to
250 tonnes per annum, or 100 to 1 000 tonnes of Benzoflex 2088 annually in the first 5 years.
Benzoflex 2088 containing the notified chemical will be formulated into various adhesive
products in Australia. The notified chemical will comprise between 10 and 20% (w/w) of the
final adhesive products. The adhesives can be sold directly to consumers or adhesive
industries. The package size will vary depending on the product, from 200 g containers
(containing up to 40 g of triethylene glycol dibenzoate) for consumers to several tonnes for
industrial use.
6. OCCUPATIONAL EXPOSURE
The notifier provided occupational exposure data on 2 manufacturing sites, which use
approximately 30% of the total import volume. The data of category and number of workers
and duration of handling are summarised in the table. The processes will be fairly uniform
across sites.
Manufacturing Number of
Category of Workers Duration
Site Workers
Site A Operators 20 6 hours/day, 230 days/year
Maintenance workers 1 1 hour/week
Quality Control workers 4 3 hours/day, 230 days/year
Warehouse workers 4 6 hours/day, 230 days/year
Site B Plant staff 15 4 hours/day, 200 days/year
Transport and storage
The product, Benzoflex 2088 containing 25% the notified chemical, will be shipped in 55
gallon drums or 33 000 pound IBCs. Warehouse workers will handle the product on arrival
into the plants. They will also take the finished products containing approximately 9 to 17%
notified chemical from the plant floor either to the finished good warehouse or directly to
wholesale stores. Occupational exposure to the notified chemical is not expected during
transport, storage and distribution, except in the event of a spill.
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Manufacture
When manufacturing a small batch, operators will weigh the required quantity into a
container manually for addition to the mixing tank. Full drums are used for large batches, the
material is pumped directly into the vertical mixing tank. Empty drums will be disposed of
without rinsing or washing. The mixing process starts when all the raw materials are added.
Benzoflex 2088 remains a liquid throughout the cold blend process. After the blending
process, the operators will carry out the packaging task to the point of shipment or storage.
The finished products contain approximately 9 to 17% notified chemical. The package size
will vary depending on the product, from 200 g containers for consumers to large containers
for industrial use. Due to the low vapour pressure of the notified chemical, very limited
inhalation exposure is expected. The main route of exposure during blending, filling and
packaging will be dermal contamination. Eye contamination from splashes may occur during
decanting. When transferring large batches, the operators can only be exposed to the notified
chemical when the connecting and disconnecting hoses.
There will be quality control staff who take spot samples during the manufacturing process.
They analyse these samples on the plant floor or in the laboratories. Dermal exposure may
occur, however, the exposure of quality control staff is expected to be low due to the small
sample sizes.
There will be several maintenance workers on call to repair manufacturing equipment. They
are typically trained and experienced former plant operators. The level and frequency of
exposure depends on the nature of the job. It is estimated that they may contact the notified
chemical for 1 hour per week per person.
All mixing tanks have specialised extraction equipment systems above the mixing area.
Ventilation systems are also in place. All operators, quality control staff and maintenance
workers wear overalls, safety glasses, hard hats, gloves and hard tipped industrial footwear.
End use
Adhesive products containing approximately 9 to 17% notified chemical may be applied
manually to the substrates to be joined, using spray roll coater, knife over roll or by numerous
other application techniques. The main route of exposure will be dermal contact. Limited
inhalation and eye exposure is expected since most adhesives are viscous liquids. Limited
information was provided on application methods and work practices. Based on the low
concentration of the notified chemical in the adhesive products, the occupational exposure
during end use is expected to be low.
When the adhesives have been dried and fixed, the adhesive products, hence the notified
chemical, will be incorporated into the joints of the articles.
7. PUBLIC EXPOSURE
Benzoflex 2088 containing up to 25% of the notified chemical will be used as a plasticiser in
adhesive products for use in the packaging industry and for domestic uses. Exposure of the
general public as a result of manufacture, transport and disposal of the product containing the
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notified chemical is assessed as being negligible. Adhesive products containing notified
chemical are to be used by the general public and the packaging industry. The general public
may make dermal and possibly ocular contact with adhesive products during the application
of these products in domestic situations.
8. ENVIRONMENTAL EXPOSURE
Release
Wastes generated at facilities manufacturing adhesive formulations are retained on site and
are used in the preparation of subsequent batches of adhesive. All spills are absorbed with
appropriate materials and disposed of into landfill. The notifier did not quantify the amount
of waste chemical likely to be lost in this manner, the quantity of material left in emptied
drums, or the fate of the drums. However, if it is assumed as a worst case that 1% of the
chemical is lost through spills and leaks during manufacturing, this equates to a release of up
to 2.5 tonnes of the chemical to the soil compartment (i.e. landfill). Similarly, if 1% of the
chemical remains in the drums after emptying and is placed into landfill, a further 2.5 tonnes
could be released. It is more likely that the drums would be sent to a drum
refurbishment/recycling facility where residual chemical would be removed with solvents
and/or steam. The waste liquids containing the residual chemical would then be treated prior
to release to the sewer, and most of the unused chemical would be recovered into a sludge or
filter cake. The sludge or filter cake would then be either incinerated or placed into landfill.
In any case, it is estimated that a maximum of 5 tonnes of the new chemical could be placed
into landfill each year as a result of waste and residuals from adhesive manufacture.
Application of the adhesives to the parts to be joined could be either manual, or (in industrial
situations) by using automated mechanical equipment including rollers and hot knife blades.
The notifier did not indicate the amount of waste adhesive generated by end users, but this is
likely to be small in industrial situations and 1% is a reasonable default figure. However,
waste percentages may be very large in the case of domestic users of small quantities of
adhesive, and it would not be unusual to find 50% of a container of glue unused before being
disposed of with domestic garbage.
The adhesives would be used in fabrication and repair of a very wide selection of articles,
which at the end of their useful lives would be either incinerated or be placed into landfill.
Because of the diverse nature of these articles it is not possible to quantify the likely fate of
old products containing the adhesives and plasticiser, and as a worst case scenario it is
assumed that all will eventually be disposed into landfill. Consequently, on the basis of these
considerations, if all the new chemical is eventually placed into landfill, a maximum of 250
tonnes per annum would be released to the soil compartment. However, since articles
containing the adhesive will be spread out across Australia, release will be diffuse.
Fate
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Aerobic Biodegradation
A test for ready biodegradability was conducted (Jenkins, 1998a) according to the Modified
Sturm Test (OECD Test Guideline 301B) which measures the rate of CO2 evolution from the
test material when incubated with sewage bacteria in culture medium. Results of this test
indicated that the chemical is readily biodegradable. Benzoflex S-358 and sodium benzoate
were added to the test vessel ?both at nominal concentrations of 10 mg organic carbon per
litre ?and the CO2 evolution monitored over a 28 day test period. The test material was
degraded 16% after 2 days, 62% after 7 days and 92% after 28 days, and since over 60%
degradation had occurred within 10 days of the 10% point being reached, the test material is
considered to be readily biodegradable. Further, comparison of the CO2 evolution rate from
this test with that from the test with sodium benzoate alone indicated that the Benzoflex S-
358 is not inhibitory to bacterial activity. Also, the sodium benzoate alone was degraded by
67% after 7 days and 83% after 29 days, indicating that the bacterial culture used in the test
was viable.
Anaerobic Biodegradation
A report on biodegradation of the compound under anaerobic conditions was supplied
(Barnes, 1998). This test measured the rate of production of biogas (i.e. carbon dioxide and
methane) using International Standards Organisation (ISO) Method ISO 11734. In this
method, samples of the test compound were digested in a suspension of anaerobic sludge
(obtained from the anaerobic digester of a metropolitan sewage plant) in an aqueous mineral
salt medium at 35 oC for period of 56 days. The volume of gas produced in the headspace
above the liquor was monitored over the test period, and comparison of this volume at any
particular time with the theoretical volume of biogas production for complete degradation
provided the degree of degradation at that time.
Since the compound has low solubility in water, the test material was dissolved in acetone (36
g/L) and 0.5 mL of this solution added to the digester. The acetone was evaporated off using
a nitrogen stream, the sludge suspension added to a volume of 120 mL and the digester vessel
sealed. The nominal concentration of the test material in the digester was consequently 150
mg/L, which equated to a nominal 100 mg/L of organic carbon. The degree of degradation as
determined from the biogas production, increased steadily from approximately 12% after 6
days to 61% after 56 days. This result indicated that the test compound is ultimately
biodegradable under anaerobic conditions. A reference test using polyethylene glycol (MW =
400 g/mol), also at a nominal concentration of 100 mg/L organic carbon, gave 67%
degradation of this compound after 14 days, and approximately 85% after 56 days, indicating
that the inoculum was viable and that the test was valid.
General
Some new chemical will be released during manufacturing processes, and is likely to be
placed into landfill. The notifier indicates that this is the preferred method for disposal. The
eventual fate of the majority of the imported chemical will be strongly linked to that of
discarded consumer articles, namely placement into landfill or incineration. As a worst case,
if all is assumed to be placed into landfill, up to 250 tonnes per annum could be released to
the soil compartment. Although the new chemical will be incorporated into the polymer mass
of the adhesive, this will degrade over time with the release of the Benzoflex S-358. The high
value for Log Koc (3.2) indicates that initially the chemical will become associated with the
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organic component of the soil, but since it is readily biodegradable it is not expected to be
persistent in this medium, and will be degraded to carbon dioxide, methane (anaerobic
conditions) and water. If articles containing the chemical are incinerated, it will be destroyed
with formation of water and oxides of carbon.
The compound is moderately water soluble (30.4 mg/L). The moderate value for Log Koc
indicates the possibility for some mobility in soil. However, it is unlikely that much chemical
would reach the water compartment as it is readily biodegradable. This, together with the low
Log Pow (3.2) and water solubility (30.4 mg/L) indicate little potential for bioaccumulation
(Connell, 1990). The notifier calculated the Bioconcentration Factor (BCF) of 58.1 which was
derived from a QSAR relating BCF to Log Pow. The equation used was ?br>
Log BCF = 0.77 x Log Pow ?0.70,
and the value of Log Pow used was the measured value of 3.2.
The ASTER data base (US EPA, 2000) also provided a QSAR estimate for the BCF in
Fathead minnow (Pimephales promelas) of 524. Both these QSAR estimated values are low
and indicate low potential for bioaccumulation.
The ASTER data (US EPA, 2000) also estimates the partitioning of the compound to the
three major environmental compartments derived from Mackay Level 1 modelling.
Calculations indicate that 42% of the compound would enter the water compartment, with the
remainder becoming associated with soils and sediments. However, these calculations take
no account of biodegradation, so may only be used as an indication of partitioning in the
present case.
9. EVALUATION OF TOXICOLOGICAL DATA
The toxicological studies on the notified chemical were performed at the Huntingdon Life
Sciences Ltd in UK with the compliance of OECD standard of Good Laboratory Practice in
the testing of chemicals and quality assurance.
9.1 Acute Toxicity
Summary of the acute toxicity of Triethylene Glycol Dibenzoate
Test Species Outcome Reference
acute oral toxicity rat LD50=5 313 mg/kg (McRae, 1998b)
acute dermal toxicity rat LD50>2 000 mg/kg (McRae, 1998a)
skin irritation rabbit Non irritating (Parcell, 1998b)
eye irritation rabbit Slight irritating (Parcell, 1998a)
skin sensitisation guinea pig Non sensitising (Coleman, 1998)
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9.1.1 Oral Toxicity (McRae, 1998b)
Species/strain: Rat/Sprague-Dawley (CD)
Number/sex of animals: 5/sex per group
Observation period: 15 days
Method of administration: Oral (gavage) doses at 2 000, 3 200, 5 000 and 6 400 mg/kg.
Test method: OECD TG 401
Mortality: 1 male at 3 200 mg/kg;
1 male and 3 females at 5 000 mg/kg; and
3 males at 6 400 mg/kg.
Clinical observations: Piloerection, hunched posture, red brown stained muzzle,
ungroomed appearance and walking on toes were seen in
most animals at all dose levels. Increased salivation,
waddling/unsteady gait, lethargy, sensitivity to handling,
respiratory distress, abnormal faeces, cold extremities, body
tremors, increased lacrimation, prostration, thin appearance,
pallid extremities, protruding eyes and partially close eyelids
were observed at one or more dosages. All symptoms
reversed by day 14 except piloerection, which was still
evident on day 15 in males at 5 000 mg/kg.
Morphological findings: A generalised congestion was observed in either all or the
majority of organs and tissues of the dead animals.
No macroscopic abnormalities were found in surviving
animals.
Comment: All deaths (1 male was killed in extremis) occurred within 3
days of dosing.
LD50: 5 537 mg/kg (males),
4 938 mg/kg (females),
5 313 mg/kg (combined sexes).
Result: The notified chemical was of very low acute oral toxicity in
rats.
9.1.2 Dermal Toxicity (McRae, 1998a)
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Species/strain: Rat/Sprague-Dawley(CD)
Number/sex of animals: 5/sex
Observation period: 15 days
Method of administration: A dermal application (2 000 mg/kg in corn oil) under
occlusive dressing for 24 hours.
Test method: OECD TG 402
Mortality: None
Clinical observations: None
Morphological findings: None
Comment: 3 female animals had either no bodyweight gain or low
bodyweight gain.
LD50: > 2 000 mg/kg
Result: The notified chemical was of low dermal toxicity in rats.
9.1.3 Inhalation Toxicity
Not provided.
9.1.4 Skin Irritation (Parcell, 1998b)
Species/strain: Rabbit/New Zealand White
Number/sex of animals: 6 males
Observation period: 72 hours
Method of administration: A single application of the notified chemical (0.5 g) in corn
oil under a semi-occlusive dressing for 4 hours.
Test method: OECD TG 404
Draize scores: Draize scores for erythema and oedema were zero for all
animals at 1, 24, 48 and 72 hours after dosing.
Result: The notified chemical was not irritating to the skin of
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rabbits.
9.1.5 Eye Irritation (Parcell, 1998a)
Species/strain: Rabbit/New Zealand White
Number/sex of animals: 6 females
Observation period: 72 hours
Method of administration: A volume of 0.1 mL of the notified chemical was placed into
the lower everted lid of one eye of each animal. The other
eye served as control.
Test method: OECD TG 405
Draize scores:
Time after instillation
Anim al 1 hour 1 day 2 days 3 days
Conjunctiva r c r c r c r c
1 2 0 2 0 0 0 0 0
2 1 0 1 0 0 0 0 0
3 1 0 1 0 0 0 0 0
4 1 0 1 0 0 0 0 0
5 1 0 1 0 0 0 0 0
6 1 0 0 0 0 0 0 0
1
see Attachment 1 for Draize scales
r = redness c = chemosis
Other Draize scores: Draize scores for cornea (density and area) and iris lesion in
all 6 animals were zero during the study.
Comment: Discharge from conjunctivae was not recorded.
Result: The notified chemical was a slight irritant to the eyes of
rabbits.
9.1.6 Skin Sensitisation (Coleman, 1998)
Species/strain: Guinea pigs/albino Dunkin- Hartley
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Number of animals: 20 males (test group);
20 males (test vehicle group);
10 males (positive control group);
10 males (vehicle control group).
Induction: Intradermal 3 pairs of intradermal injections (0.1 mL) were made on
injection (Day 1) shaved shoulder area of each animal:
Test Group
?Freund's Complete Adjuvant (FCA) with water (1:1 v/v);
?100% notified chemical;
?100% notified chemical in FCA (1:1, v/v).
Test Vehicle Group
?Freund's Complete Adjuvant (FCA) with water (1:1 v/v);
?Alembicol D;
?Alembicol D in FCA (1:1, v/v).
Control Group
?Freund's Complete Adjuvant (FCA) with water (1:1 v/v);
?Hexyl cinnamic aldehyde (HCA) in Alembicol D (10%,
v/v);
?10% HCA in a mixture of Alembicol D and FCA (1:1,
v/v).
Control Vehicle Group
As described in the Test Vehicle Group
Induction: Topical Dermal application of 10% sodium lauryl sulphate (0.5 mL)
application (Day 6) in petrolatum.
(Day 7)
Test Group
Dermal application of 100% notified chemical (0.4 mL)
under occlusive dressing for 48 hours.
Control Group
Dermal application of 10% HCA in Alembicol D under
occlusive dressing for 48 hours.
Test Vehicle Group and Control Vehicle Group
Dermal application of Alembicol D under occlusive dressing
for 48 hours.
Challenge: Topical Test Group and Test Vehicle Group
application (Day 21) One occluded application of 50% notified chemical in
Alembicol D (0.2 mL) and one occluded application of
100% notified chemical (0.2 mL) were applied to the flank
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NA/817 16/34
for 24 hours.
Control Group and Control Vehicle Group
These animals were treated similarly as the above groups
with the exception that the notified chemical was replaced
with HCA.
Test method: OECD TG 406
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NA/817 17/34
Challenge outcome:
Challenge Test Group Test Vehicle Positive Control Control vehicle
concentration Group Group*** Group
24 h* 48 h* 24 h 48 h 24 h 48 h 24 h 48 h
100% **0/20 0/20 0/20 0/20 9/9 9/9 0/10 0/10
50% 0/20 0/20 0/20 0/20 8/9 8/9 0/10 0/10
* time after patch removal.
** number of animals exhibiting positive response.
*** one animal was killed for humane reasons prior to challenge application.
Comment: Slight erythema was observed in Test Group animals after
receiving intradermal injections and topical applications.
Slight erythema was also seen in the Control Group animals.
Result: The notified chemical was not sensitising to the skin of
guinea pigs
9.2 Repeated Dose Toxicity (Paffett, 1999)
Species/strain: Rat/Cr1:CD BR
Number/sex of animals: 10/sex per gruop
Method of administration: Dietary
Dose/Study duration: Group 1: 0 mg/kg/day (control);
Group 2: 400 mg/kg/day;
Group 3: 1 000 mg/kg/day;
Group 4: 1 600 mg/kg/day;
Group 5: 2 200 mg/kg/day.
The duration of treatment was 13 weeks. Group 1 and 5 had
extra 10/sex as the recovery groups which had 4 week
recovery period after treatment.
Test method: OECD TG 408
Clinical observations:
Hair loss was observed in both sexes in Group 5 during treatment and recovery period.
Bodyweight gain in Group 4 and 5 were decreased in both sexes. This was more apparent
in males as a slight reduction in food intake was noted in males at high level doses. At the
end of recovery period, the bodyweight loss reversed fully in females and partially in males.
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NA/817 18/34
There were no other clinical signs considered to be treatment related.
Clinical chemistry/Haematology
Very slight increases in alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) were seen at week 5 in both sexes in Group 5 and females in Group 4, and at week
13 in males of Group 5 associated with periportal hepatocyte hypertrophy. At week 17, this
difference was not apparent and there was no residual hepatic pathology in recovery groups.
Males of Group 4 and 5 had an increase in red blood cell count at week 5 which recovered
by week 13. They also had a non-cellular specific decrease in white blood cell count at
week 5 and 13.
A decrease of urinary sodium, potassium and pH levels was noted in both sexes of Group 5,
and reduced pH levels, in males of Group 4 at week 13.
Histopathology:
Periportal hepatocyte hypertrophy was observed in both sexes of Group 5 at the end of
treatment. This pathological change reversed after 4 week recovery period.
An increase incidence and degree of haemosiderosis in spleen was seen in Group animals,
and became less significant after 4 week recovery period.
Comment:
No treatment related differences were observed between the control and test groups on
water consumption, ophthalmic examination, organ weights and other tests. Lower
bodyweight gain, haematological changes and changes in blood clinical chemistry were
apparent at 1 600 and 2 200 mg/kg/day but not at 1 000 mg/kg/day. These effects were
selected to establish the NOEL.
Result:
The NOEL established for this 13 week dietary study is 1 000 mg/kg/day.
9.3 Genotoxicity
9.3.1 Salmonella typhimurium and Escherichia coli Reverse Mutation Assay (Kitching,
1998)
Strains: Salmonella typhimurium TA1535, TA1537, TA98 and
TA100; and Escherichia coli CM891 WP2 trp urvA
Metabolic activation: Liver fraction (S9 mix) from rats pretreated with Aroclor
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NA/817 19/34
1254.
Concentration range: Test 1 (plate incorporation assay):
0, 5, 15, 50, 150, 500, 1 500 and 5 000 礸/mL for all strains
in the absence and presence of metabolic activation.
Test 2 (pre-incubation assay):
0, 50, 150, 500, 1 500 and 5 000 礸/mL for all strains in the
absence and presence of metabolic activation.
Positive control (-S9):
N-ethyl-N'-nitro-N-nitrosoguanidine for TA1535 (5
礸/plate), TA100 (3 礸/plate) and CM891 (2 礸/plate), 9-
aminoacridine for TA1537 (80 礸/plate), and 2-nitrofluorene
for TA98 (1 礸/plate).
Positive control (+S9):
2-aminoanthracene for TA1535 (2 礸/plate), CM891 (10
礸/plate), and benzo[a]pyrene (5 礸/plate) for TA1537,
TA98 and TA100.
DMSO was used as the vehicle for all above studies.
Test method: OECD TG 471 and 472
Comment: No toxicity was observed in either mutation test.
No substantial increases in revertant colony numbers of any
of the test strains were observed following the treatment
with the notified chemical at any dose level, in the presence
or absence of S9 mix in either mutation test.
The mean revertant colony counts for the vehicles were
within the historical range. The positive controls caused
marked increases of revertant colony numbers in the
presence or absence of S9 mix in both mutation test.
Result: The notified chemical was non mutagenic under the
conditions of the test
9.3.2 Chromosomal Aberration Assay in Human Lymphocytes (Akhurst, 1998)
Cells: Human lymphocyte culture
Metabolic activation Liver fraction (S9 mix) from rats pretreated with Aroclor
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NA/817 20/34
system: 1254.
Dosing schedule: The notified chemical was dissolved in DMSO and tested in
duplicate cultures in 2 tests with or without metabolic
activation.
Metabolic Experiment/ Test concentration Controls
Activation Study Number
-S9 First test Treatment/recovery time Positive: mitomycin C
(0.8 礸/mL)
=3/18 hours
6.25, 12.5, 25, 50, 100*, Negative: DMSO
200*, 400* and 800 礸/mL
Second test Treatment time=21 hours
50, 100, 150, 200*, 300*, Positive: mitomycin C
400*, 500* and 600 礸/mL (0.4 礸/mL)
Negative: DMSO
+S9 First test Treatment/recovery time Positive:
=3/18 hours cyclophosphamide
6.25, 12.5, 25, 50, 100*, (20 礸/mL)
200*, 400* and 800*
礸/mL Negative: DMSO
Second test Treatment/recovery time
=3/18 hours
50, 100, 200*, 400*, 500,
600, 700 and 800* 礸/mL
DMSO ?dimethylsulphoxide
* cultures selected for metaphase analysis
Test method: OECD TG 473
The notified chemical showed toxic at 400 and 800 礸/mL
Comment:
without S9 and 800 礸/mL with S9 in the first test, and
showed toxic at 600 礸/mL without S9 in the second test.
Precipitates were observed at the 235.5 礸/mL in culture
medium when DMSO was used as the solvent.
The notified chemical did not show indication of inducing
chromosomal aberrations in the absence or presence of
metabolic activation in this in vitro cytogenetic test system.
Both positive control compounds caused large, statistically
significant increases in the proportion of aberrant cells.
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NA/817 21/34
Result: The notified chemical was non clastogenic under the
conditions of the test.
9.3.3 Mammalian Cell Gene Mutation Test in vitro in the Mouse (Adams, 1998)
Cells: Mouse lymphoma L5178Y cells
Metabolic activation Liver fraction (S9 mix) from rats pretreated with Aroclor
system: 1254.
Dosing schedule: The notified chemical was dissolved in DMSO and tested in
triplicate cultures in 2 tests with or without metabolic
activation.
Treatment time =3 hours;
Sampling time=24 & 48 hours.
Metabolic Experiment/ Test concentration Controls
Activation Study Number
-S9 First test 25, 50, 100, 150, 200, and Positive control:
400 礸/mL methyl methanesulphonate
50, 100, 150, 200, 300, (10 礸/mL in DMSO).
Second test
and 400 礸/mL
+S9 First test 25, 50, 100, 150, 200, and Positive control:
400 礸/mL 20-methylcholanthrene
50, 100, 150, 200, 300, (2.5 礸/mL in DMSO).
Second test
and 400 礸/mL
Test method: OECD TG 476
Comment: Concentrations used in Test 1 and 2 were selected based
upon the results from a preliminary test.
No substantive increases in mutant frequency were observed
after treatement with the notified chemical in either test.
Both positive control compounds caused significant
increases in mutant frequency in both tests.
Result: The notified chemical was not of mutagenic potential under
the conditions of the test.
9.4 Other Studies
FULL PUBLIC REPORT 31 October,
2000
NA/817 22/34
The notifier provided 3 other studies on the notified chemical. The estrogenic activity study
was performed by Bioqual Inc, USA in 1997 with a quality assurance statement and in
compliance with OECD GLP regulations. Both the in vitro digestion study and excretion
study of the notified chemical were conducted by the Food and Drug Research Laboratories,
USA in 1965 and 1967, respectively. The level of reporting detail was low and these 2
studies had no statements for quality assurance or compliance with GLP guidelines.
9.4.1 Estrogenic Activity Study (Reel, 1997)
Species/strain: Adult ovariectomized female rat/Sprague-Dawley (CD)
Number/sex of animals: 10/group
Test substance: Benzoflex S-358 (96.9%% triethylene glycol dibenzoate)
Method of administration: Oral (gavage)
Dose/Study duration: The duration of treatment was 7 days. Diethylstilbestrol
(DES) was employed as the positive control. Both the
notified chemical and the positive control substance were
administered in corn oil.
Group 1: 250 mg/kg/day;
Group 2: 700 mg/kg/day;
Group 3: 1 400 mg/kg/day;
Group 4: 2 100 mg/kg/day;
Group 5: 2 800 mg/kg/day;
Group 6: 5 mL/kg/day corn oil (vehicle control);
Group 7: 2.5 礸/kg/day DES (positive control);
Group 8: 5 礸/kg/day DES (positive control);
Group 9: 10 礸/kg/day DES (positive control).
Clinical observations:
Groups 1-4: One rat in Group 3 died on day 5 due to a gavage dosing error. Piloerection
and soft stool were observed in test animals. All surviving rats appeared normal at
necropsy on day 7.
Group 5: Five rats in this test group showed clinical signs of toxicity after treatment
including piloerection, red discharge on the muzzle, tremors, lethargy, scruffy coat, pale
colour, convulsions, hyperactive and vocalization. Two of them were found dead on day 5
and 6, respectively. The 8 surviving rats had no gross abnormalities at necropsy on day 7.
Vaginal Cornification:
Vaginal cornification was not observed in the rats treated with the notified chemical
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NA/817 23/34
(Groups 1-5) during the study.
The positive control, DES, resulted in a dose-dependent induction of vaginal cornification.
Body and Uterine Weights:
The final body weights for the animals treated with the notified chemical (Groups 1-5) were
not significantly different (p>0.05) from that of the vehicle controls (Group 6). No increase
in uterine weight or uterine/bodyweight ratio was found in rats of Groups 1-5 when
compared to the vehicle control (Group 6).
DES suppressed body weight gain in a dose dependent manner over the 7 day dosing
period, and induced a dose dependent increase in uterine weight and in uterine/bodyweight
ratio.
Comment:
Currently, there are no OECD test guidelines for endocrine disrupting effects. Guidelines
are under development.
This study was performed according to an in-house method, based on several published
scientific papers. The endpoints, vaginal cornification, increase in uterine weight and
increase in uterine/bodyweight ratio were determined in this study.
Result:
The notified chemical did not exhibit estrogenic activity as determined by endpoints,
vaginal cornification, increase in uterine weight to body weight ratio and uterine weight
under test conditions.
9.4.2 In Vitro Digestion Study (Kross, 1965)
The study description implies that this assay was done to ascertain the breakdown of this
chemical when used as a food additive.
Digestion systems: System 1: Simulated intestinal fluid containing pancreatin
(pH adjusted) prepared according to United States
Pharmacopoeia (USP) XVIth revision;
System 2: Similar to System 1 except that 1 g freshly
prepared rat liver homogenate replaced the pancreatin.
Sample size and duration: A 100 mg sample was added to 50 mL of System 1 or 2 for a
digestion period of 4 hours.
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NA/817 24/34
Degree of Hydrolysis: The degree of hydrolysis of the notified chemical was
determined by digest in 6N HCl for 4 hours.
Test method: Similar to that described in USP.
Result: Under test conditions, the liver homogenate produced
greater (58%) hydrolytic breakdown than intestinal fluid
(33%). Study authors presumed the breakdown products to
be benzoic acid and triethylene glycol, and suggested that
digestion would be virtually complete under in vivo
conditions.
9.4.3 Excretion Study in Rats and Dogs (Morgoreidge, 1967)
Species/strain: Young adult FDRL rats and adult beagle dogs.
Number/sex of animals: Study 1: 1/sex dogs, 1/sex rats;
Study 2: 1/sex dogs, 1/sex rats;
Study 3: 1 female dog.
Observation period: Study 1: 72 hours;
Study 2: 120 hours (5 days);
Study 3: 0-24, 25-72 and 73-120 hours.
Urine and feces samples were collected separately during the
observation period. Radioactivity was measured and
reported for urine and combined urine and faeces.
Oral (gavage, 5 mg/kg [C14] labeled notified chemical in
Method of administration:
propylene glycol solution).
The radioactive C14 was in the carbonyl position of the
Comment:
benzoic acid moiety of the ester. The radioactive
metabolites were assumed to include the known metabolites,
hippuric acid and benzoyl glucuronic acid.
In dogs, absorption was higher in males than females. In
both species, total recovery increased over time (measured
up to 120 hours), but highest excretion occurred, in both
urine and faeces, in the first 24 hours. Most recovered label
was found in urine (96-100% and 58-99% in rats and dogs,
respectively).
Result: The notified chemical was readily and rapidly absorbed from
the gastrointestinal tract of both rats and dogs, and its
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NA/817 25/34
benzoic acid metabolites were rapidly excreted.
9.5 Overall Assessment of Toxicological Data
The notified chemical was of very low acute oral toxicity (LD50=5 313 mg/kg) and low acute
dermal toxicity (LD50>2 000 mg/kg) in rats. It was not an skin irritant but a slight eye irritant
in rabbits. The notified chemical was not a skin sensitiser in guinea pig.
A 13 week dietary study on the notified chemical was performed in rats. The control and
highest dose groups also had a recovery period of 4 weeks. Lower bodyweight gain,
haematological changes and changes in blood clinical chemistry were observed in rats at
1 600 mg/kg/day and above. Based on these effects, the NOEL established for this study is
1 000 mg/kg/day.
Three in vitro genotoxicity studies were provided. The notified chemical was not mutagenic
in bacteria, in human lymphocyte culture, or in mouse lymphoma L5178Y cells.
There were 3 other studies provided in the submission. The notified chemical did not exhibit
estrogenic activity based on the endpoints of vaginal cornification, increase in uterine weight
to body weight ratio and increase in uterine weight. The excretion study indicated that the
notified chemical was readily and rapidly absorbed from the gastrointestinal tract of both rats
and dogs, and its metabolites were rapidly excreted. This result was consistent with the in
vitro digestion study which suggested a virtually complete digestion under in vivo conditions.
According to NOHSC Approved Criteria for Classifying Hazardous Substances (National
Occupational Health and Safety Commission, 1999), the notified chemical is not classified as
a hazardous substance.
10. ASSESSMENT OF ENVIRONMENTAL EFFECTS
Due to the rapid biodegradation of the chemical, it was not possible for the notifier to obtain
reliable ecotoxicity data against aquatic organisms. In preliminary test work under static
conditions (medium replacement every 24 hours) with no fish, daphnia or algae present, the
concentration of the test material could not be maintained within 20% of the nominal
concentrations over the test periods required by the relevant protocols. This explanation is
acceptable although analytical data supporting this assertion would have been of use. A
QSAR estimate on the acute toxicity of the compound against the fish species Pimephales
promelas (fathead minnow) from the ASTER data base (USEPA, 2000) was LC50 of 4 mg/L.
The notifier did supply test reports on the acute toxicity of the compound to earthworms, and
on the inhibition of respiration for sewage bacteria.
Test Species Result
Acute Toxicity to Earthworm Eisenia foetida LC50 > 1 000 mg/kg
FULL PUBLIC REPORT 31 October,
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NA/817 26/34
[OECD TG 207] NOEL > 1 000 mg/kg
Inhibition of Bacterial Sewage bacteria EC50 >100 mg/L
Respiration [OECD TG 209]
Earthworm s
A test on the acute toxicity of the new compound to earthworms was submitted (Johnson,
1998). Groups of 40 worms were placed in soil containing nominally 0 (control), 95, 171,
309, 556 and 1,000 mg/kg of the test compound, and their condition was monitored over a 14
day period. There were no mortalities among the worms over the test period, nor were any
other adverse effects observed. Accordingly, the results of this test indicate that the material
is non toxic to this species. However, it is noted that the compound is rapidly biodegraded in
aqueous media (see above), and it is likely that the worms were not exposed to the full
nominal test levels of the compound over the 14 day period.
Sewage Bacteria
A test on the inhibition of bacterial respiration was conducted (Jenkins, 1998b). The test
substance was suspended in artificial sewage at nominal loadings of 1, 10 and 100 mg/L using
a 30 minute period of sonication to assist dispersion. The test flasks were inoculated with
sewage sludge bacteria and aerated for 30 minutes. Following aeration, the contents of the
flasks were poured into darkened 300 mL BOD bottles fitted with oxygen sensing electrodes.
The rate of oxygen consumption was measured for the dispersions, and compared with that in
a control vessel. None of the tests indicated any significant inhibition of bacterial respiration
compared with the controls, and it was concluded that the new chemical is not toxic to
sewage bacteria up to the limits of its water solubility.
In contrast to tests with the new chemical, a reference test conducted with 3,5-dichlorophenol
gave an EC50 of 8.3 mg/L, indicating the viability of the bacterial culture used.
It is also to be noted that in the tests for ready biodegradation (see above), no inhibitory
effects of the compound on bacterial activity was observed. This is in agreement with the
present result.
11. ASSESSMENT OF ENVIRONMENTAL HAZARD
The environmental hazard from the notified chemical is not expected to be high when it is
used for the manufacture of adhesives as indicated in the notification. The adhesives will be
used within industry and by the general domestic consumer.
Very little of the chemical is expected to be released during manufacturing of adhesive
formulations, and release is estimated at a maximum of 2% of import quantity, or a maximum
of 5 tonnes year. It is expected that this would be placed into landfill. Release of the
compound during industrial use of adhesives is expected to be small, although comparatively
larger proportions could be released when adhesives are used by the general public. The
associated waste would also be placed into landfill. Old articles containing the new chemical
such as furniture or books would most likely be discarded into landfill or be incinerated.
FULL PUBLIC REPORT 31 October,
2000
NA/817 27/34
Assuming none is incinerated, a maximum of 250 tonnes could be placed into landfill each
year.
The compound is readily biodegradable under aerobic conditions, and is ultimately
degradable under anaerobic conditions. Once placed into landfill the compound is likely to be
slowly released as a consequence of the degradation of the polymer matrix of the adhesives in
which it is encapsulated, and is then expected to become associated with the organic
component of soils and sediments. Subsequently the compound will be degraded through
biological processes to carbon dioxide, methane (in anaerobic conditions) and water.
The compound exhibited no toxicity to earthworms, with a 14 day LC50 > 1 000 mg/kg. Due
to the rapid biodegradation of the chemical, it was not possible to generate ecotoxicity data
for the compound against aquatic species although ASTER data predicted a 96 hr LC50 for
fathead minnow of 4 mg/L. However, very little of the compound is expected to enter the
water compartment so exposure to aquatic organisms is expected to be low. The new
chemical is readily biodegradable and the low value for Log Pow (3.2) and water solubility
(30.4 mg/L) indicate low potential for bioaccumulation. This is supported by two low QSAR
estimates of the BCF (58 and 524).
12. ASSESSMENT OF PUBLIC AND OCCUPATIONAL HEALTH AND SAFETY
EFFECTS
The notified chemical, Benzoflex S-358, was of very low acute oral toxicity and low acute
dermal toxicity in rats. It was not a skin irritant but a slight eye irritant in rabbits, and not a
skin sensitiser in guinea pigs. The NOEL established from a repeat dose dietary study in rats
for Benzoflex S-358 is 1 000 mg/kg/day. The notified chemical was not mutagenic in
bacteria, in human lymphocyte culture, or in mouse lymphoma cells. In addition, the notified
chemical did not exhibit estrogenic activity in rats. An excretion study and an in vitro
digestion study indicated that the notified chemical was readily and rapidly absorbed from the
gastrointestinal tract in both rats and dogs, and its metabolites were rapidly excreted.
According to NOHSC Approved Criteria for Classifying Hazardous Substances (National
Occupational Health and Safety Commission, 1999), Benzoflex S-358 is not classified as a
hazardous substance.
Besides Benzoflex S-358, the import product, Benzoflex 2088 contains 45% diethylene
glycol dibenzoate (CAS No 120-55-8) and 23% dipropylene glycol dibenzoate (CAS No
27138-31-4). The notifier provided some toxicity data for diethylene glycol dibenzoate and
dipropylene glycol dibenzoate in the material safety data sheet (MSDS). Both ingredients
were of very low acute oral and inhalation toxicity, and low acute dermal toxicity. They were
not skin irritants or sensitisers, but caused very slight conjunctival irritation in rabbit eyes.
These two chemicals were not mutagenic in bacteria or mammalian cells, or clastogenic in
Chinese hamster lung cell in vitro. Treated rats did not exhibit estrogenic activity and had
NOELs of 1 000 mg/kg/day following repeated dosing for 13 weeks.
Occupational Health and Safety
FULL PUBLIC REPORT 31 October,
2000
NA/817 28/34
Waterside, warehouse and transport workers will only be exposed to the notified chemical in
the event of an accident or damage to packaging. The occupational health risk to these
workers is negligible.
At the manufacturing sites, the blending, filling and packaging processes are expected to be
within closed systems. When preparing small batches, operators will add the product
containing 25% the notified chemical into blending tanks manually. For large batches, this
process will be mechanical. The quality control staff and maintenance workers will handle
the notified chemical in small qualities and for short periods of time. Slight eye irritation may
occur on acute exposure to the notified chemical, hence, workers should wear goggles when
handling the notified chemical in an open process. The notified chemical has been used
overseas for a number of years, but the notifier has not observed any work related injuries or
diseases in workers exposed to this chemical. Considering the low toxicity hazard of the
notified chemical and the overall low occupational exposure, the health risk for workers at the
manufacturing sites is low.
End users will handle the adhesive products containing approximately 9 to 17% of the
notified chemical. They may apply the adhesives manually or mechanically. Based on the
low percentage of the notified chemical in adhesives and low toxicity of the notified
chemical, the health risk for end use workers handling the adhesive products containing the
notified chemical is low. The notified chemical becomes fixed into the articles after the
adhesive dries.
Public Health
Exposure of the general public as a result of manufacture, transport and disposal of the
product containing the notified chemical is assessed as negligible. Although adhesive
products containing notified chemical are to be used in the packaging industry, they will also
be used by the general public in domestic situations. Dermal and possible ocular contact with
products containing the notified chemical are likely during use. However, the risk to public
health is considered to be minimal due to the low concentration of the notified chemical in
products to be used by the public, the low dermal toxicity and slight eye irritancy of the
notified chemical.
13. RECOMMENDATIONS
To minimise occupational exposure to Benzoflex S-358 the following guidelines and
precautions should be observed:
Safety goggles should be selected and fitted in accordance with Australian Standard
?br>
(AS) 1336 (Standards Australia, 1994) to comply with Australian/New Zealand
Standard (AS/NZS) 1337 (Standards Australia/Standards New Zealand, 1992);
Spillage of the notified chemical should be avoided. Spillages should be cleaned up
?br>
promptly with absorbents which should be put into containers for disposal;
Good personal hygiene should be practised to minimise the potential for ingestion;
?br>
FULL PUBLIC REPORT 31 October,
2000
NA/817 29/34
A copy of the MSDS should be easily accessible to employees.
?br>
If products containing the notified chemical are hazardous to health in accordance with the
NOHSC Approved Criteria for Classifying Hazardous Substances (National Occupational
Health and Safety Commission, 1999), workplace practices and control procedures consistent
with State and territory hazardous substances regulations must be in operation.
14. MATERIAL SAFETY DATA SHEET
The MSDS for Benzoflex 2088 containing the notified chemical were provided in a format
consistent with the National Code of Practice for the Preparation of Material Safety Data
Sheets ((National Occupational Health and Safety Commission, 1994).
This MSDS was provided by the applicant as part of the notification statement. It is
reproduced here as a matter of public record. The accuracy of this information remains the
responsibility of the applicant.
15. REQUIREMENTS FOR SECONDARY NOTIFICATION
Under the Act, secondary notification of the notified chemical may be required if any of the
circumstances stipulated under subsection 64(2) of the Act arise. No other specific conditions
are prescribed.
16. REFERENCES
Adams K (1998) Benzoflex S-358: mammalian cell mutation assay, Project No. VCL
279/973590, Huntingdon Life Sciences Ltd, Cambridgeshire, England.
Akhurst L (1998) Benzoflex S-358: In vitro mammalian chromosome aberration test in
human lymphocytes, Project No. VCL 280/973041, Huntingdon Life Sciences Ltd,
Cambridgeshire, England.
Barnes SP (1998) Benzoflex S-358: Evaluation of ultimate anaerobic biodegradability by
measurement of biogas production; Huntingdon Life Sciences Ltd, report for Velsicol
Chemical Corp. VCL/289; 23 October 1998.
Coleman D (1998) Benzoflex S-358: Skin sensitization to the guinea-pig, Project No. VCL
275/973101/SS, Huntingdon Life Sciences Ltd, Cambridgeshire, England.
Connell DW (1990) Bioaccumulation of Xenobiotic Compounds;CRC Press.
FULL PUBLIC REPORT 31 October,
2000
NA/817 30/34
Jenkins WR (1998a) Benzoflex S-358: Assessment of ready biodegradability ?Modified
Sturm Test; Huntingdon Life Sciences Ltd, report for Velsicol Chemical Corp. VCL/287; 5
November 1998.
Jenkins WR (1998b) Benzoflex S-358: Activated sludge ?Respiration inhibition test;
Huntingdon Life Sciences Ltd, report for Velsicol Chemical Corp. VCL/286; 5 November
1998.
Johnson AJ (1998) Benzoflex S-358: Acute Toxicity to the Earthworm; Huntingdon Life
Sciences Ltd, report for Velsicol Chemical Corp. VCL/294; 27 November 1998.
Kitching J (1998) Benzoflex S-358: Bacterial mutation aqssay (S. typhimurium and E. coli),
Project No. VCL 278/973339, Huntingdon Life Sciences Ltd, Cambridgeshire, England.
Kross R (1965) In vitro digestion experiments on triethylene glycol dibenzoate, Project No.
86975c, Food and Drug Research Laboratories, USA.
McRae L (1998a) Benzoflex S-358: Acute dermal toxicity to the rat, Project No. VCL
291/973247/AC, Huntingdon Life Sciences Ltd, Cambridgeshire, England.
McRae L (1998b) Benzoflex S-358: Acute oral toxicity to the rat, Project No. VCL
274/973566/AC, Huntingdon Life Sciences Ltd, Cambridgeshire, England.
Morgoreidge K (1967) Studies on the excretion of triethylene glycol dibenzoate in rats and
dogs, Project No. 87452, Food and Drug Research Laboratories, USA.
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2000
NA/817 31/34
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FULL PUBLIC REPORT 31 October,
2000
NA/817 32/34
Attachment 1
The Draize Scale (Draize, 1959) for evaluation of skin reactions is as follows:
Erythema Formation Rating Oedema Formation Rating
No erythema 0 No oedema 0
Very slight erythema (barely perceptible) 1 Very slight oedema (barely perceptible) 1
Well-defined erythema 2 Slight oedema (edges of area well-defined 2
by definite raising
Moderate to severe erythema 3 Moderate oedema (raised approx. 1 mm) 3
Severe oedema (raised more than 1 mm 4
Severe erythema (beet redness) 4
and extending beyond area of exposure)
The Draize scale (Draize et al., 1944) for evaluation of eye reactions is as follows:
CORNEA
Opacity Rating Area of Cornea involved Rating
No opacity 0 none 25% or less (not zero) 1
1 slight 25% to 50% 2
Diffuse area, details of iris clearly
visible
Easily visible translucent areas, details 2 mild 50% to 75% 3
of iris slightly obscure
Opalescent areas, no details of iris 3 Greater than 75% 4
visible, size of pupil barely discernible moderate
Opaque, iris invisible 4 severe
CONJUNCTIVAE
Redness Rating Chemosis Rating Discharge Rating
No discharge
0 none
Vessels normal 0 none
0 none No swelling
Any swelling above Any amount different
1 slight
Vessels definitely 1 slight
1
injected above normal normal from normal
slight
2 mild
Obvious swelling with Discharge with
More diffuse, deeper 2 mod.
2 mod.
moistening of lids and
crimson red with partial eversion of lids
adjacent hairs
individual vessels not
Swelling with lids half-
easily discernible
3 mod. Discharge with 3 severe
closed
moistening of lids and
Diffuse beefy red 3 severe
Swelling with lids half- hairs and considerable
4 severe
closed to completely area around eye
closed
IRIS
Values Rating
Normal 0 none
Folds above normal, congestion, swelling, circumcorneal injection, iris reacts to light 1 slight
No reaction to light, haemorrhage, gross destruction 2 severe
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FULL PUBLIC REPORT
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MSDS
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FULL PUBLIC REPORT
NA/ 34/34
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