Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-10-19 to 2011-12-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
With acceptable restrictions. GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted 30 May 2008
Deviations:
yes
Remarks:
3 animals were subject to reduced exposure time ranging between >4 to 24 hours
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24th Feb, 1987
Deviations:
yes
Remarks:
3 animals were subject to reduced exposure time ranging between >4 to 24 hours
GLP compliance:
yes (incl. QA statement)
Remarks:
Certificate dated 6 April 2009
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzyl methacrylate
EC Number:
219-674-4
EC Name:
Benzyl methacrylate
Cas Number:
2495-37-6
Molecular formula:
C11H12O2
IUPAC Name:
benzyl 2-methylprop-2-enoate
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl methacrylate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- WISTAR rats Crl:WI(Han) (full barrier)
- Age at study initiation: males: approx. 13 weeks, females: approx. 14 weeks
- Weight at study initiation: males: 250-267 g, females: 205-223 g
- Fasting period before study: no
- Housing: separate IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding, full barrier in air-conditioned room
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 2011-09-20 to 2011-11-10

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: gauze-dressing with non-irritating tape, fixed with additional dressing in suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): n/a (undiluted)
- Constant volume or concentration used: yes (single dose)

Duration of exposure:
24 h (except for 3 test animals which unwrapped themselves overnight, leading to a shortened application period of 4 to 24 hours)
For the animals which unwrapped themselves, no signs of toxicity and significant dermal irritation were observed. As at the 4 h control observation the dressing was tight on all animals, it is very likely that the 3 animals unwrapped themselves clearly after the 4 h period. It can be expected that these animals have been exposed to the test item partially also by the oral route, while grooving, in addition to the dermal route.
It is concluded that the abbreviated exposure period has no effect on the overall result and the classification of the test item, and that a sufficient estimation of the dermal toxicity is ensured.
The validity of the study is not affected and according to animal welfare reasons it was decided not to repeat the study.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation several times on day of dosing (at least once during first 30 minutes and with special attention given during the first 4 hours post-dose). Symptoms were recorded as soon as noticed. Thereafter, daily observations for clinical signs until end of observation period. All abnormalities were recorded. Animals were weighed on day 1 (prior to application of dose) and on day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
-- In case of gross pathological changes, tissues were preserved for a possible histopathological evaluation.
-- The treated areas of skin were examined daily for signs of primary skin irritation. Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404, adopted 24th April 2002.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
All animals survived until the end of the observation period of 14 days.
Clinical signs:
No signs of systemic toxicity were observed
Body weight:
A slight weight loss was recorded for 1 of 5 female animals during the first week, but 4 of 5 female animals showed weight gain during the second week and stagnation was recorded for 1 of 5 female animals. According to discussion by the study authors, the effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded. The male animals showed weight gain during the first and the second week of the observation.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.
Other findings:
Signs of irritation:
- very slight erythema (grade 1, reversible within 8 days) was observed in 1/5 females on days 4, 5, and 7; this animal showed also eschar (up to day 10) and desquamation (up to day 12)
- eschar, desquamation and scratches were observed in one further female, without leading to scoring
- all effects were reversible within 13 days - females with reduced exposure time due to unwrapping showed either no effects or only non-scored eschar (day 5 to 7) or scratches (day 7)
- No skin irritation was observed at the males.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The LD50-value for acute dermal toxicity of the test substance BNMA is > 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (adopted 24th Feb, 1987), EU Method B.3 (adopted 30 May 2008), 5 male and 5 female young adult WISTAR Crl: WI(Han) rats were dermally exposed to BNMA (98.37%) for 24 hours under a semiocclusive dressing to approx. 10% of body surface area at doses of 2000 mg/kg bw. Animals then were observed for 14 days.

No animal died. Erythema grade 1 was observed in 1 of 5 female animals. Eschar and scratches were observed in 3 of 5 female animals. Desquamation was observed in 2 of 5 female animals. No signs of irritation were found for the male animals. All signs of irritation were reversible within the observation period. No clinical signs of systemic toxicity were observed. Weight gain was positive and within normal range, except for 3 female rats which temporarily lost weight in the first week. No macroscopic substance related pathologic organ findings were noted during necropsy.

Dermal LD50

Males > 2000  mg/kg bw

Females > 2000  mg/kg bw

Combined > 2000  mg/kg bw

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