File No: NA/495
August 1997
NATIONAL INDUSTRIAL CHEMICALS NOTIFICATION
AND ASSESSMENT SCHEME
FULL PUBLIC REPORT
PPT
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 Worksafe Australia which also conducts the occupational health &
safety assessment. The assessment of environmental hazard is conducted by the
Department of the Environment, Sport, and Territories and the assessment of
public health is conducted by the Department of Health and Family Services.
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, Worksafe Australia, 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
For Enquiries please contact the Administration Coordinator at:
Street Address: 92 Parramatta Rd Camperdown, NSW 2050, AUSTRALIA
Postal Address: GPO Box 58, Sydney 2001, AUSTRALIA
Telephone: (61) (02) 9577-9466 FAX (61) (02) 9577-9465
Director
Chemicals Notification and Assessment
NA/495
FULL PUBLIC REPORT
PPT
1. APPLICANT
Novo Nordisk Bioindustrial Pty Ltd of Unit 3, 22 Loyalty Road NORTH ROCKS NSW
2151 has submitted a limited notification statement in support of their application
for an assessment certificate for 10H-phenothiazine-10-propionic acid; hereafter
referred to as PPT. No claims for exempt information were made by the notifier,
and the assessment report is published here in its entirety.
2. IDENTITY OF THE CHEMICAL
Chemical Name: 10H-phenothiazine-10-propionic acid
Chemical Abstracts Service
(CAS) Registry No.: 362-03-8
Other Names: 10-phenothiazine propionic acid
3-(10-phenothiazinyl) propionic acid
-(10-phenothiazinyl) propionic acid
3-phenothiazine-10-yl-propionic acid
10-(propionic acid) phenothiazine
PPA
PPT
Trade Name: DeniLiteTM (3% notified chemical)
DeniLiteTM Plus (9% notified chemical)
Molecular Formula: C15H13NO2S
Structural Formula:
S
N
CO2H
Molecular Weight: 271.3
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Method of Detection high performance liquid chromatography (HPLC)
and Determination:
Spectral Data: ultraviolet/visible (UV/Vis), infrared (IR) and
nuclear magnetic resonance spectra were
provided by the notifier; major characteristic
peaks were found in the IR spectrum at: 2 500-
3 300, 1 710, 1 590, 1 450, 1 000-1 400 and 400-
1 000 cm-1
3. PHYSICAL AND CHEMICAL PROPERTIES
Appearance at 20癈 the notified chemical in pure form is an off white
and 101.3 kPa: crystalline powder
Melting Point: 160 - 164.5癈
Boiling Point: > 180癈 (decomposes before boiling)
Specific Gravity: 1.351
1.0 x 10-4 kPa at 25癈
Vapour Pressure:
51.2 ?0.9 mg/L (pH approximately 6.7)
Water Solubility:
Partition Co-efficient
log P ow = 1.87 at 22 ?0.5癈
(n-octanol/water):
Hydrolysis as a Function
of pH: T1/2 at pH 4.0, 7.0, 9.0 > 1 year (estimated)
Adsorption/Desorption: not provided
Dissociation Constant: pKa is approximately 5-6 (in 50% ethanol)(see
comments below)
Surface Activity: 62.4 mN/m
> 105 祄
Particle Size: 28.2% (% mass)
60.0 - 105 祄 3.3%
30.0 - 60.0 祄 30.7%
10.4 - 30.0 祄 29.5%
0.5 - 10.4 祄 8.3%
(particle size determined by image analysis)
Flash Point: non-flammable
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Flammability Limits: non-flammable
Autoignition Temperature: no relative self-ignition temperature below its
melting range
Explosive Properties: not explosive
Reactivity/Stability: not oxidising
Comments on Physico-Chemical Properties
Tests were performed according to OECD test guidelines (1) at facilities complying
with OECD Principles of Good Laboratory Practice.
The notified chemical is hydrolytically stable over the environmental pH range.
No data has been provided for the adsorption/desorption behaviour of the
chemical. The moderate water solubility and relatively low partition coefficient
would indicate that the chemical is not likely to adsorb strongly to soils and
sediments.
The dissociation constant was determined in a 50% ethanolic solution because of
the relatively low water solubility of the chemical. The value is typical for a
carboxylic acid.
The notified chemical is not expected to be surface active. By definition, a chemical
has surface activity when the surface tension is less than 60 mN/m (2).
4. PURITY OF THE CHEMICAL
Degree of Purity: 97-100%
Toxic or Hazardous
Impurities: none
Non-hazardous Impurities 10-H-phenothiazine (0-1%)
(> 1% by weight): polyacrylate (0-2%)
Additives/Adjuvants: none
5. USE, VOLUME AND FORMULATION
The notified chemical will not be manufactured or reformulated in Australia. It will
be used in the textile industry as a enzyme mediator in oxido-reductase catalysed
reactions and will be imported as a component of two end use products;
DeniLiteTM and DeniLiteTM Plus (containing 3.0% and 9.0% of PPT, respectively).
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These products will be used for the bleaching of textile dyes without the use of
chlorine based chemicals.
Up to one tonne of the notified chemical will be imported per annum for each of the
first five years.
6. OCCUPATIONAL EXPOSURE
End use products containing the notified chemical will be imported in 25 kg jerry
cans. Waterside, warehouse and transport workers are unlikely to come into
contact with the notified chemical except in the event of an accident or leaking
packaging.
Dermal exposure to the notified chemical is possible when workers pour end use
products into closed systems such as dosing tanks, prior to addition to industrial
washing machines. Inhalation exposure is unlikely at this stage, although
accidental ocular contact may occur. The notifier states that workers are expected
to be handling the end use products for only several minutes per day.
Mixing of DeniLiteTM with water in an industrial washing machine will form low
concentrations of free radicals as an intermediate in the bleaching process. The
notifier indicates that it is not known if the free radical form of the notified chemical
will form in the event of a spillage or skin/eye contact. Presumably, however, free
radical formation would occur if the spilt product contacted water. The toxicological
significance of this intermediate is also not known.
Dermal exposure to an oxidised derivative, 10H-phenothiazine-10-propionic acid 5-
oxide (PPTO) is likely when workers are unloading textiles from industrial washing
machines. Concentrations of both the notified chemical and the oxidised derivative
are both expected to be very low, however, as there are several rinsing steps which
follow immediately after treatment of the fabric.
Worker exposure to other potentially hazardous components of the end use
products may also occur.
7. PUBLIC EXPOSURE
Products containing the notified chemical will be used for bleaching of dyes such
as indigo (used for dyeing denim) to produce a highly abraded textile appearance.
At the completion of the bleaching process, the notified chemical, PPT, will be
totally oxidised to PPTO. After bleaching, the textiles will be washed, and the
notified claims that all PPTO will be removed.
The notifier has indicated that the chemical will not be present in textiles used for
clothing manufacture. However, minimal quantities of the oxidised form of the
notified chemical may not wash out. If small amounts of the oxidised form is
retained in the textiles, dermal exposure could occur following contact. However,
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exposure should be minimal.
Minimal public exposure may result from disposal of the unused products which
contain the notified chemical, or accidental spillage of the products during
transport and storage. However, adequate measures are described by the notifier
to minimise the risk of public exposure during disposal, or in the event of
accidental spillage.
8. ENVIRONMENTAL EXPOSURE
Release
No release or exposure to the environment is expected from this chemical during
transportation, with the exception of accidental spillage. There are adequate
instructions on the Material Safety Data Sheets (MSDS) for the products containing
the notified chemical to cope with accidental spillage.
After emptying, the jerry cans which contain the notified chemical will be rinsed into
industrial washing machines leaving trace amounts in cans. Empty cans will be
disposed of to landfill.
The notified chemical undergoes rapid conversion to the oxidised derivative PPTO
during treatment of the fabric (the structure of PPTO is shown below). Because of
this oxidation, the notified chemical will not be released with the effluent from the
fabric treatment process. Almost all the imported notified chemical will be
discharged to the sewer as PPTO after dilution in on-site sewerage treatment
plants.
PPTO
O
S
N CO2H
Fate
PPTO will be discharged into the sewer at low levels. The partition coefficient and
water solubility of PPTO have not been determined. Calculation of the log Kow for
PPT and PPTO, using atom/fragment contribution method developed by Syracuse
Research Corporation (3), shows a drop of greater than 2 orders of magnitude in
log K ow between PPT and PPTO. Hence, PPTO is not expected to adsorb strongly.
Additionally, due to its high polarity the water solubility of PPTO would be
significantly greater than that of PPT.
Although no biodegradation data needs to be provided for chemicals imported at
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rates less than 1 000 kg per annum according to the Act, the notifier has provided
biodegradation data for both PPT and PPTO. Both PPT and PPTO were examined
for biodegradation potential using EEC Directive 92/69, Part C.4-C (Modified Sturm
Test), and OECD Test Guideline 301B (1, 2). At levels of 10 and
15 mgC/L (mg carbon/litre), PPT showed cumulative CO2 production values of 3
and 7% of theoretical values, respectively. PPTO was no more than 1% degraded
at 10 and 15 mgC/L and no degradation was observed at 15 mgC/L. These results
indicate that neither PPT or PPTO are readily biodegradable under the conditions
of the test. Bacterial inhibition tests using a modified closed bottle test (OECD
Method 301D (1)) were conducted for both PPT and PPTO. The biodegradation of
the reference material, sodium benzoate, was examined over five days at
concentrations of 10 and 15 mgC/L. Both PPT and PPTO were found to have no
inhibitory effect on the biodegradation of the reference material under these
conditions.
Given the expected low partition coefficient, moderately high water solubility and
lack of biodegradability it is anticipated that PPTO will remain dissolved in waste
water and will not be removed during sewerage treatment, according to the
SimpleTreat model (4).
PPT is not expected to bioaccumulate due to its moderately high water solubility
and low partition coefficient (5). As it is anticipated that PPTO would have higher
water solubility and a lower partition coefficient it would also not be expected to
bioaccumulate.
9. EVALUATION OF TOXICOLOGICAL DATA
Toxicological data are not required for chemicals with import volumes less than
1 tonne per annum, according to the Act. However, the following toxicological data
were provided by the notifier for PPT.
9.1 Acute Toxicity
Summary of the acute toxicity of PPT
Test Species Outcome Reference
acute oral toxicity rat LD 50 > 2 000 mg/kg (6)
acute dermal toxicity rat LD 50 > 2 000 mg/kg (7)
inhalation toxicity rat LC 50 > 5.32 mg/L (8)
skin irritation rabbit non-irritant (9)
eye irritation rabbit slight irritant (10)
skin sensitisation guinea pig non-sensitiser (11)
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9.1.1 Oral Toxicity (6)
Species/strain: rat/CD strain
Number/sex of animals: 5/sex
Observation period: 15 days
Method of administration: single dose of 2 000 mg/kg given by gavage;
vehicle was 0.5% (w/v) methyl cellulose in
purified water
Clinical observations: none
Mortality: none
Morphological findings: none
Test method: similar to EEC Directive 92/69/EEC (2)
LD 50: > 2 000 mg/kg
Result: the notified chemical is of low oral toxicity in
rats
9.1.2 Dermal Toxicity (7)
Species/strain: rat/CD strain
Number/sex of animals: 5/sex
Observation period: 15 days
Method of administration: single dose of 2 000 mg/kg applied to an
intact skin site and moistened with purified
water; occlusive dressing applied for
24 hours; the dressing was removed and
excess test material wiped away
Clinical observations: there were no local signs of reaction to
treatment; one male showed pigmented
orbital secretion on day 2
Mortality: none
Morphological findings: none
Test method: similar to EEC Directive 92/69/EEC (2)
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LD 50: > 2 000 mg/kg
Result: the notified chemical was of low dermal
toxicity in rats
9.1.3 Inhalation Toxicity (8)
Species/strain: rat/CD strain
Number/sex of animals: 5/sex
Observation period: 14 days
Method of administration: the test material was passed through an
ultracentrifugal mill fitted with a 0.2 mm
screen; material was packed into a Wright
Dust Feed Mechanism; atmosphere
generated by suspending material scraped
from the surface of the compressed powder
in a stream of dry air; the exposure period
was 4 hours; the nominal atmospheric
concentration was 8.12 mg/L; the achieved
chamber concentration was 5.32 mg/L; the
mass median equivalent aerodynamic
diameter was 6.73 祄
Clinical observations: during the exposure period a number of
animals exhibited soiled and wet fur, reduced
respiratory rate, exaggerated respiration,
struggling in the restraint tube and excessive
salivation; hunched posture and wet fur was
noted in all animals during the 2 hours
following exposure; all animals appeared
normal from the day following exposure to the
end of the study
Mortality: none
Morphological findings: none
Test method: similar to EEC Directive 92/69/EEC (2)
LC 50: > 5.32 mg/L
Result: the notified chemical was of low inhalation
toxicity in rats
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9.1.4 Skin Irritation (9)
Species/strain: rabbit/New Zealand White
Number/sex of animals: 3/male
Observation period: 72 hours
Method of administration: 0.5 g of the test substance was moistened
with purified water and applied to a 6 cm2
intact dorsal skin site; skin covered by gauze
and semi-occlusive dressing for 4 hours;
excess material removed from test site after
dressing removed; observations made at
1 hour, 1, 2 and 3 days after removal of
dressing and scored according to the
method of Draize (12)
Draize scores (12): all Draize scores were zero
Test method: similar to EEC Directive 92/69/EEC (2)
Result: the notified chemical was not a skin irritant in
rabbits
9.1.5 Eye Irritation (10)
Species/strain: rabbit/New Zealand White
Number/sex of animals: 2 male/1 female
Observation period: 72 hours
Method of administration: 0.1 g of the test material was placed in the
conjunctival sac of the left eye of each animal;
right eye served as control
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Draize scores (12) of unirrigated eyes:
Time after instillation
Animal 1 hour 1 day 2 days 3 days
Cornea no corneal effects were noted
Iris
1 1 0 0 0
2 1 0 0 0
3 0 0 0 0
ra cb dc ra cb dc ra cb dc ra cb dc
Conjunctiv
a
1 2 0 0 2 0 0 2 0 0 0 0 0
2 2 0 2 2 0 0 1 0 0 0 0 0
3 1 0 1 2 0 1 0 0 0 0 0 0
1
see Attachment 1 for Draize scales
a b
chemosis c discharge
redness
Test method: similar to EEC Directive 92/69/EEC (2)
Result: the notified chemical was a slight eye irritant
in rabbits
9.1.6 Skin Sensitisation (11)
Species/strain: guinea pig/Dunkin-Hartley
Number of animals: 15/sex
Induction procedure: Day 1: 3 pairs of intradermal injections:
- 0.1 mL Freund's complete adjuvant
(FCA): purified water (1:1(v/v))
- 0.1 mL of 3% concentration of test
material in propylene glycol
- 0.1 mL of 3% concentration of test
material in FCA: propylene glycol
(1:1 (v/v))
Day 7: test area treated with 0.5 mL 10%
(w/v) sodium lauryl sulfate in
petrolatum
Day 8: occluded application of 0.6 mL test
material (50% in propylene glycol) for
48 hours
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Challenge procedure: Day 22: occluded application of 0.03 mL test
material (50% and 10% in propylene
glycol) for 24 hours
Challenge outcome:
Test animals Control animals
Challenge
concentratio 24 hours* 48 hours* 24 hours 48 hours
n
10% 0/20** 0/20 0/10 0/10
50% 0/20 0/20 0/10 0/10
* time after patch removal
** number of animals exhibiting positive response
Test method: similar to EEC Directive 92/69/EEC (2)
Result: the notified chemical was not a skin
sensitiser in guinea pigs
9.2 Repeated Dose Toxicity (13, 14)
The results of two repeat dose oral toxicity studies were submitted by the notifier.
One of these is summarised below (13). The second study dosed rats for a 28
day period at 25, 150 and 1 000 mg/kg/day (14). A brief comment on the outcome
of the second study is provided in under the `results' heading of this section.
Species/strain: rat/CD strain
Number/sex of animals: 40/sex
Method of administration: gavage; vehicle was 0.5% (w/v) methyl
cellulose
Dose/Study duration:: test material administered daily for a total of
28 days:
control: 0 mg/kg/day
low dose: 50 mg/kg/day
mid dose: 150 mg/kg/day
high dose: 750 mg/kg/day
all animals were sacrificed at the end of the
treatment period
Clinical observations: the following symptoms were observed in
animals which died or were killed in extremis
during the study: post-dose salivation and
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piloerection, underactiveness, prostration,
poor reflexes; survivors in the high dose
group also exhibited underactiveness and
excess salivation; pink stained, ungroomed
fur were noted in these animals from week 3
food consumption, body weight gain and food
utilisation of animals in the high dose group
were lower than controls
Mortality: 2 males and 3 females from the high dose
group died or were killed in extremis during
the study; these deaths occurred by day 6
Clinical packed cell volumes, haemoglobin
chemistry/Haematology: concentration and erythrocyte numbers were
lower in animals from the high dose group
when compared with controls; total leucocyte
and platelet numbers of animals in this
group were higher than controls
plasma alanine and aspartate amino-
transferase activities and total bilirubin, urea
and creatinine concentrations were higher in
animals from the high dose group than
controls
Histopathology: adrenal, kidney, liver and testes weights of
animals of the high dose group were higher
than controls
at necropsy of the animals which survived the
test period, 2 animals in the high dose group
were found to have areas of change on the
kidneys; cystic and non-cystic tubular dilation
with or without proteinaceous casts;
interstitial inflammation and basophilic
tubules and less frequent pyelonephritis and
capsular fibrosis were observed in animals
from the high dose group
enlargement and congestion of the spleen
was observed in a number of the high dose
animals
Test method: similar to OECD guidelines (1)
Result: treatment of rats with the notified chemical at
the high dose (750 mg/kg/day) induced a
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number of changes in the kidneys and red
blood cells indicative of organ toxicity; results
of the second repeat dose study (14) also
found evidence of kidney toxicity at high
(1 000 mg/kg/day) doses
9.3 Genotoxicity
9.3.1 Salmonella typhimurium Reverse Mutation Assay (15)
Strains: Salmonella typhimurium TA 98, TA 100,
TA 1535 TA 1537
25 - 2500 礸/plate; vehicle was DMSO;
Concentration range:
assays were carried out in the presence or
absence of rat liver S9 fraction
Test method: similar to OECD guidelines (1)
Result: the notified chemical was not mutagenic in
the bacterial strains tested in the presence or
absence of metabolic activation; concurrent
positive controls demonstrated the sensitivity
of the assay
9.3.2 Micronucleus Assay in the Bone Marrow Cells of the Mouse (16)
Species/strain: mouse/CD1 strain
Number and sex of animals: 90/sex
Doses: 250, 500 or 1 000 mg/kg/day for 2
consecutive days; vehicle was 1% methyl
cellulose; animals were sacrificed 24 or 48
hours after final treatment
Method of administration: gavage
Test method: similar to OECD guidelines (1)
Comments: signs of systemic toxicity were noted in
several animals from the high dose group
and 2 animals died following the second
administration; one treated male from the
48 hour high dose group showed increased
levels of polychromatic erythrocytes which
influenced statistical analysis; treated males
and females at the 24 hour sample and
females at the 48 hour sample did not exhibit
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increased frequencies of polychromatic
erythrocytes when compared with concurrent
controls
Result: the notified chemical did not produce a
statistically significant increase in
polychromatic erythrocytes (following non-
parametric testing) when compared with
controls
9.3.3 Chromosomal Aberrations in Cultured Human Lymphocytes (17)
Doses: without S9 mix:
21 hour harvest: 25-200 礸/mL
45 hour harvest: 12.5-200 礸/mL
(cells exposed continuously for the test
period)
with S9 mix:
21 hour harvest: 50-1 000 礸/mL
45 hour harvest: 50-800 礸/mL
(cells exposed for 3 hours and harvested 18
or 42 hours later)
Test method: similar to OECD Guidelines for Testing of
Chemicals (1)
Result: the notified chemical showed clear evidence
of clastogenic activity in the presence of
metabolic activation (S9 mix), although only at
cytotoxic concentrations (800 礸/mL in the
first test and 600 礸/mL in the second test)
9.3.4 Unscheduled DNA synthesis in Rat Liver (18)
Species/strain: rat/Wistar
Number and sex of animals: 15/male
Doses: 632.5 or 2 000 mg/kg; animals were
sacrificed 2-4 hours or 12-14 hours after
treatment; hepatocytes were isolated and
examined for unscheduled DNA synthesis
Method of administration: gavage; vehicle was 1% (w/v) methyl
cellulose
Test method: UKEMS Test Guidelines (19)
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Result: the notified chemical did not induce
unscheduled DNA synthesis under the
conditions employed
9.4 Preliminary Teratology Study (20)
Species/strain: rat/CD strain
Number/sex of animals: 24/female
Method of administration: gavage; vehicle was 0.5% (w/v)
methylcellulose
Dose/Study duration: test material administered daily to pregnant
rats from day 6 to day 15 inclusive; scheduled
doses were as follows:
control: 0 mg/kg/day
low dose: 100 mg/kg/day
mid dose: 300 mg/kg/day
high dose: 1 000 mg/kg/day
all animals were sacrificed on day 20 of
gestation and uterine contents examined
Clinical observations: 3 females receiving 1 000 mg/kg/day were
killed in extremis on day 7 of gestation as a
result of treatment; the remainder of the
animals in this group were removed from the
study
Comments: macroscopic examination of females from
groups dosed with 100 or 300 mg/kg/day at
necropsy showed no treatment-related signs;
litter responses were similar in all groups
(as assessed by the numbers of corpora
lutea, implantations and viable young, extent
of pre- and post- implantation losses and
foetal and placental weights); macroscopic
examination of the foetuses did not reveal
any findings considered to be treatment
related
Test method: similar to EEC Directive 92/69/EEC (2)
Result: doses of up to 300 mg/kg/day for a 10 day
period during gestation did not induce
teratogenic effects in a preliminary teratology
study
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9.5 Overall Assessment of Toxicological Data
The notified chemical was of low acute oral and dermal toxicity to rats
(LD 50 > 2 000 mg/kg in both studies). The LC50 was found to be greater than
5.32 mg/L in an inhalation toxicity study in the same species, indicating that
the notified chemical is also of low toxicity when administered via this route.
It was not a skin irritant when tested in rabbits but caused slight eye
irritation in the same species. The notified chemical was not a skin
sensitiser in guinea pigs.
A 28-day repeat dose oral toxicity study in rats indicated that treatment with
high doses of the notified chemical (750 mg/kg/day) resulted in some
kidney and erythrocyte effects. A second study confirmed kidney toxicity at
high doses (1 000 mg/kg/day)
Genotoxicity studies indicated that the notified chemical was not mutagenic
in a bacterial reverse mutation study and did not induce unscheduled DNA
synthesis in rat hepatocytes in an in vivo/in vitro study. Clastogenic activity
was noted in an in vitro human lymphocyte study, however, this was only
observed at cytotoxic concentrations. Some evidence of chromosome
damage was noted in an in vivo mouse micronucleus assay at high doses.
The results of these tests indicate that the notified chemical may be weakly
genotoxic.
A preliminary teratology study indicated that maternal doses of up to
300 mg/kg/day did not induce abnormalities, as assessed by foetal
numbers and development.
Based on the results of toxicological studies summarised above, PPT
would not be classified as hazardous according to the Approved Criteria for
Classifying Hazardous Substances (21).
10. ASSESSMENT OF ENVIRONMENTAL EFFECTS
Although no ecotoxicological data needs to be provided for chemicals imported at
rates less than 1 tonne per annum according to the Act, the following ecotoxicity
studies have been supplied by the notifier for PPT and PPTO. The tests were
carried out according to OECD Test Methods (1).
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Species Test Results
PPT
fathead minnow Acute Toxicity LC 50 = 88.1 mg/L
(OECD Method 203)
Pimephales NOEC = 11.2 mg/L
Promelas
Daphnia magna Acute Immobilisation NOEC = 3.12 mg/L
(OECD Method 202, Part 1) EC50 = 8.42 (7.13-10.3) mg/L
algae Growth Inhibition NOEbC = 0.067 mg/L (72 hour)
Selenastrum (OECD Method 201) NOErC = 0.89 mg/L (72 hour)
capricornutum EbC50 = 2.03 mg/L (72 hour)
ErC50 = 6.58 mg/L (0-72 hour)
PPTO
fathead minnow Acute Toxicity NOEC = 95.1 mg/L
(OECD Method 203)
Pimephales
Promelas
Daphnia magna Acute Immobilisation NOEC = 81.8 mg/L
(OECD Method 202, Part 1)
algae Growth Inhibition NOEC = 37.7 mg/L (72 hour)
Selenastrum (OECD Method 201) EbC50 = 88.7 mg/L (72 hour)
capricornutum ErC50 > 101 mg/L (0-72 hour)
In the acute toxicity test for fish of PPT only two measured concentrations showed
lethal effects. The LC50 was estimated to be 88.1 mg/L, based on 50% mortality at
this concentration. No unusual observations were made during the acute toxicity to
fish for PPTO. The effects were only examined at one measured concentration in a
limit test.
For PPT the highest measured concentration at which Daphnia immobilisation
was 5% or less (also the NOEC) after 48 hours was 3.12 mg/L; at the highest
measured concentration 95% immobilisation was observed. The effect of PPTO
on daphnia
was only examined at one measured concentration in a limit test. No immobility or
adverse effects were observed at this concentration.
The algal EbC50 and ErC50 for PPT were determined by non-linear interpolation
between two concentrations that bracket the 50% effect level. For PPTO, the 50%
inhibition of the growth rate was not observed and therefore the ErC50 must be
greater than 101 mg/L.
The ecotoxicity data for the notified chemical, PPT, is moderately toxic daphnia and
algae and slightly toxic to fish, while PPTO is likely to be practically non-toxic to fish,
daphnia and algae. As noted above, neither PPT or PPTO is likely to inhibit
sewerage micro-organisms.
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11. ASSESSMENT OF ENVIRONMENTAL HAZARD
The notifier has estimated a predicted environmental concentration (PEC) of
6.25 ppb of PPTO as a result of discharge from a large textile plant to the sewer
(based on the use of 5 kg of PPT, with a waste water flow of 4 000 m3 per day and
a surface dilution factor of 200). The major user of the notified chemical will be in
Adelaide and the discharge from the textile plants waste water treatment system is
expected to be treated at the Bolivar sewerage treatment works (average flow rate
of between 130 and 160 ML per day). The discharge of 5 kg of PPT as PPTO into
this sewerage system would result in a concentration of 40 ppb in discharge from
the Bolivar sewerage treatment works. This would undergo a further 10 fold
dilution in receiving waters to give a PEC of 4.0 ppb. This concentration is four
orders of magnitude lower than the lowest NOEC observed for algae (the most
sensitive species). Thus, the discharge of PPTO from textile plants is not expected
to be hazardous to aquatic organisms. Assuming that the PPT was discharged (ie
no oxidation occurred) the PEC would be approximately 3.8 ppb. This level is
around three orders of magnitude lower than the lowest OEC observed for algae.
Thus, it would not be hazardous to aquatic organisms. Dilution rates in other
capital cities are likely to be similar or greater.
The environmental hazard from the proposed use the notified chemical and its
resulting oxidised form is rated as low.
12. ASSESSMENT OF PUBLIC AND OCCUPATIONAL HEALTH AND SAFETY
EFFECTS
The occupational health risk posed to transport workers is negligible under normal
circumstances, as they will only be handling unopened jerry cans of products
containing the notified chemical.
Workers in textile processing factories will be exposed to products containing
relatively low concentrations of the notified chemical for several minutes per day.
Results of toxicological studies in animals indicate that PPT is unlikely to be
acutely toxic, and will not cause skin irritation or sensitisation if repeated skin
contact occurs. Based on the outcome of rabbit studies, some eye irritation may
result if accidental ocular exposure occurs in the workplace. Based on the results
of genotoxicity studies, which showed PPT to have weak genotoxic activity,
personal protective equipment should be worn when handling end use products
containing the notified chemicals. Given that end-use products contain relatively
low concentrations of PPT, however, and that effects in genotoxicity studies and a
repeat-dose study were seen only at high doses, adverse health effects following
long-term use of PPT are unlikely. Based on the expected low worker exposures
and the results of toxicity studies, the risk posed to workers in textile processing is
low.
The notifier states that normal handling precautions should be taken to prevent
exposure to other components of the end use products, which include ethoxylated
FULL PUBLIC REPORT 19
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fatty alcohol (skin and eye irritation potential) and enzyme products (potential for
sensitisation by inhalation).
Textiles treated with the notified chemical will be used for clothing. In the unlikely
event that the oxidised derivative, PPTO is retained in the textiles, the amount
would be minimal and should therefore pose a negligible hazard to the public.
The potential for minor public exposure exists during transport and disposal of
products containing the notified chemical, This is minimised by the recommended
practices during storage and transportation.
13. RECOMMENDATIONS
To minimise occupational exposure to PPT, the following guidelines and
precautions should be observed:
? It is good work practice to wear industrial clothing which conforms to the
specifications detailed in Australian Standard (AS) 2919 (22) and occupational
footwear which conforms to Australian and New Zealand Standard (AS/NZS)
2210 (23) to minimise exposure when handling any industrial chemical;
? Impermeable gloves or mittens should conform to AS 2161 (24);
? Spillage of products containing the notified polymer should be avoided,
spillages should be cleaned up promptly and put into containers for disposal;
? Good personal hygiene should be practised to minimise the potential for
ingestion;
? A copy of the MSDS should be easily accessible to employees.
Workers should be aware that DeniLiteTM and DeniLiteTM Plus contain other
potentially hazardous ingredients, and appropriate precautions should be taken in
the workplace to avoid exposure to these components.
14. MATERIAL SAFETY DATA SHEET
The MSDS for a product containing the notified chemical was provided in
accordance with the National Code of Practice for the Preparation of Material Safety
Data Sheets (25).
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.
FULL PUBLIC REPORT 20
NA/495
15. REQUIREMENTS FOR SECONDARY NOTIFICATION
Under the Act, secondary notification of the notified chemical shall be required if
any of the circumstances stipulated under subsection 64(2) of the Act arise.
If conditions of use are varied, greater exposure to the public to the notified
chemicals may occur. In such circumstances, further information may be required
to assess the hazards to public health. The additional information should include
toxicology data on PPTO and data on PPTO retention in bleached and washed
textiles.
16. REFERENCES
1. Organisation for Economic Co-operation and Development 1995-1996,
OECD Guidelines for the Testing of Chemicals on CD-Rom, OECD, Paris.
2. European Economic Community (EEC) 1992, 'Methods for the
Determination of Physico-Chemical Properties', in EEC Directive 92/69,
Annex V, Part A, EEC Publication No. L383, EEC.
3. Environmental Science Centre - Syracuse Research Corporation , On line
LOGKOW Demo, Location: http://esc.syrres.com.
4. European Commission 1996, Technical Guidance Document in Support of
Commission Directive 93/67/EEC on Risk Assessment for New Notified
Substances and Commission Regulation (EC) No 1488/94 on Risk
Assessment for Existing Substances. Part IV, ECSC-EC-EAEC, Brussels,
672-673.
5. Connell, D.W. 1989, 'General characteristics of organic compounds which
exhibit bioaccumulation', in Bioaccumulation of Xenobiotic Compounds,
CRC Press, Boca Raton.
6. Rees, P. 1995, 10H-Phenothiazine-10-propionic acid: Acute Oral Toxicity
Study in the Rat, Project no., 94/NLE043/1299, Pharmaco LSR Ltd, England.
7. Rees, P. 1995, 10H-Phenothiazine-10-propionic acid: Acute Percutaneous
Toxicity Study in the Rat, Project no., 94/NLE091/1250, Pharmaco LSR Ltd,
England.
8. May, K. 1995, 10H-Phenothiazine-10-propionic acid: Acute Inhalation
Toxicity Study in the Rat, Project no., 94/NLE058/1089, Pharmaco LSR Ltd,
England.
9. Rees, P. 1995, 10H-Phenothiazine-10-propionic acid: Acute Dermal
Irritation Test in the Rabbit, Project no., 94/NLE044/1300, Pharmaco LSR
Ltd, England.
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10. Rees, P. 1995, 10H-Phenothiazine-10-propionic acid: Acute Eye Irritation
Test in the Rabbit, Project no., 94/NLE045/1301, Pharmaco LSR Ltd,
England.
11. Rees, P. 1995, 10H-Phenothiazine-10-propionic acid: Delayed Contact
Hypersensitivity in the Guinea Pig, Project no., 94/NLE046/1126, Pharmaco
LSR Ltd, England.
12. Draize, J.H. 1959, 'Appraisal of the Safety of Chemicals in Foods, Drugs and
Cosmetics', Association of Food and Drug Officials of the US, vol. 49, pp. 2-
56.
13. Johnson, I. 1995, 10H-Phenothiazine-10-propionic acid: Four-week Oral
Toxicity Study in the Rat, Project no., 95/NLE170/1161, Huntingdon Life
Sciences Ltd, England.
14. Johnson, I. 1996, 10H-Phenothiazine-10-propionic acid: Four-week Oral
Toxicity Study in the Rat, Project no., 95/NLE047/0787, Huntingdon Life
Sciences Ltd, England.
15. May, K. 1995, 10H-Phenothiazine-10-propionic acid: Assessment of
Mutagenic Potential in Histdine Auxotrophs of Salmonella typhimurium (the
Ames Test), Project no., 94/NLE048/1283, Pharmaco LSR Ltd, England.
16. McEnaney, S. 1995, PPT: Induction of Micronucei in the Bone Marrow of
Treated Mice Following Oral Administration, Project no., 665/114, Corning
Hazleton (Europe), England.
17. Edwards, C. 1995, 10H-Phenothiazine-10-propionic acid: An in vitro test for
Induction of Chromosome Damage: Cytogenetic Study in Cultured Human
Peripheral Lymphocytes, Project no., 94/NLE049/1009, Pharmaco LSR Ltd,
England.
18. Clare, C. 1995, PPT: Measurement of Unscheduled DNA Synthesis in Rat
Liver Using an in vivo/in vitro Procedure, Project no., 0665/120, Corning
Hazleton (Europe), England.
19. Kennelly, J., R, W., Ashby, J., Lefevre, P., Burlinson, B., Benford, D., Dean, S.
& Mitchell, I.d.G. 1993, 'In vivo Rat Liver UDS assay', in Supplementary
Mutagenicity Tests UKEMS Recommended Procedures, Cambridge
University Press, England, pp. 52-77.
20. Burns, L. 1995, 10H-Phenothiazine-10-propionic acid: Preliminary
Teratology Study in the Rat, Project no., 94/NLE060/0846, Pharmaco LSR
Ltd, England.
21. National Occupational Health and Safety Commission 1994, Approved
Criteria for Classifying Hazardous Substances [NOHSC:1008(1994)],
Australian Government Publishing Service, Canberra.
FULL PUBLIC REPORT 22
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22. Standards Australia 1987, Australian Standard 2919-1987, Industrial
Clothing, Standards Association of Australia, Sydney.
23. Standards Australia/Standards New Zealand 1994, Australian/New Zealand
Standard 2210-1994, Occupational Protective Footwear, Standards
Association of Australia/Standards Association of New Zealand,
Sydney/Wellington.
24. Standards Australia 1978, Australian Standard 2161-1978, Industrial Safety
Gloves and Mittens (excluding electrical and medical gloves), Standards
Association of Australia, Sydney.
25. National Occupational Health and Safety Commission 1994, National Code
of Practice for the Preparation of Material Safety Data Sheets
[NOHSC:2011(1994)], Australian Government Publishing Service, Canberra.
FULL PUBLIC REPORT 23
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Attachment 1
The Draize Scale for evaluation of skin reactions is as follows:
Erythema Formation Rating Oedema Formation Rating
No erythema 0 No oedema 0
Very slight erythema (barely 1 Very slight oedema (barely 1
perceptible) perceptible)
Well-defined erythema 2 Slight oedema (edges of area well- 2
defined by definite raising
Moderate to severe erythema 3 Moderate oedema (raised approx. 1 3
mm)
Severe erythema (beet redness) 4 Severe oedema (raised more than 1 4
mm and extending beyond area of
exposure)
The Draize scale 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
Diffuse area, details of iris clearly 1 slight 25% to 50% 2
visible
Easily visible translucent areas, 2 mild 50% to 75% 3
details of iris slightly obscure
Opalescent areas, no details of iris 3 Greater than 75% 4
visible, size of pupil barely moderate
discernible
Opaque, iris invisible 4 severe
CONJUNCTIVAE
Redness Rating Chemosis Rating Discharge Rating
Vessels normal 0 none No swelling 0 none No discharge 0 none
Vessels definitely 1 Any swelling above 1 slight Any amount different 1 slight
injected above normal slight normal from normal
More diffuse, deeper 2 mod. Obvious swelling 2 mild Discharge with 2 mod.
crimson red with with partial eversion moistening of lids
individual vessels not of lids and adjacent hairs
easily discernible
Swelling with lids 3 mod. Discharge with 3
Diffuse beefy red 3 half-closed moistening of lids severe
severe and hairs and
Swelling with lids 4 considerable area
half-closed to severe around eye
completely 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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