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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
DATA QUALITY: Study was conducted in accordance with a recognized scientific procedure for determining the acute dermal toxicity of a test substance, following GLP regulations. The study meets national and international scientific standards and provides sufficient information to support the conclusions regarding the acute dermal toxicityof n-Butyl Methacrylate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Supplier: Du Pont
- Name of test material (as cited in study report): n-Butyl athacrylate
- Physical state: liquid
- Analytical purity: 99.49 %
- Purity test date: no data
- Lot/batch No.: 19845
- Expiration date of the lot/batch: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hare Marland, Hewitt, NJ, USA
- Age at study initiation: young adult
- Weight at study initiation: 2550 +/- 103 g for males and 2536 +/- 59 g for females
- Housing: singly in stainless steel , wire-mesh cages
- Diet (e.g. ad libitum): Purina certified high fiber rabbit chow #5325
- Water (e.g. ad libitum): tap water
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 190 cm²
- % coverage: 10
- Type of wrap if used: oclusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with soap and water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The day before dosing each rabbit's hair  was shaved between the scapular and lumbar region of the back. Animals  were fitted with a plastic Elizabethan collar toprevent ingestion. The  test material was then spread evenly over a gauze pad (about 190 sq. cm or  10% of the bodysurface area) and then this was applied to the exposed  skin site and held in contact by impervious bandages for 24 hours. After 24  hours the bandages were removed and the skin sites washed with soap and  water. Dermal effects were scoredaccording to Draize. Animals were  observed for mortality,body weight change (days 1, 7 adnd 14) and general  behavior throughout the study. All animals were subjected to a  gross necropsy after a 14 day observation period.
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
There were no deaths. 
Clinical signs:
Slight to moderate erythema but no edema was observed in all animals 1 day after application of the test substance. Red spots vere observed in the treated skin of 1 animal. By day 4 after application, no or moderate to severe erythema but no edema vas observed. Six animals exhibited thickening of the skin and 1 exhibited superficial necrosis. By day 7, mild to severe erythema and, no to severe edema vere observed. Four animals exhibited superficial necrosis. Epidermal scaling, thickening of the skin, and sloughing vere also observed. By day 12, mild to severe erythema and no to severe edema vere observed. Superficial necrosis vas observed in 7 animals; areas of necrosis were observed in 1 of these animais. Epidermal scaling, thickening of the skin, sloughing, and hair loss vere also observed. Additionally, 1 animal exhibited fissuring with bleeding. By.day 14, superficial necrosis was observed in 3 animals; 2 of these exhibited areas of necrosis. Mild to severe erythema and no to severe edema, eschar, epidermal scaling, thickening of the skin, sloughing, and hair loss were still present.
Body weight:
Weight losses of 1-3% occurred in some rabbits 1 day after application of the test substance. One of these rabbits appeared not to be eating 1 or 2 days after application.
Gross pathology:
Treatment-related discoloration vas noted in the treated area of 4 male and 2 female rabbits at necropsy. Other gross observations vere believed to be spontaneous and/or incidental lesions. No target organ vas identified.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
In a valid guideline study the acute dermal LD0 in rabbits was >2000 mg/kg bw.
Executive summary:

In an OECD 402 and GLP study, a single dose of n-butyl methacrylate was applied to the shaved, intact skin of 5 male and 5 femaleNew Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were observed for 14 days following application.

No rabbits died within 14 days after dosing. No to severe erythema and no to severe edema were observed in the treated rabbits during the study. Superficial necrosis was observed in 1 rabbit on day 4 after application of the test substance and in most other rabbits by day 12 after application. Two rabbits also exhibited necrosis during the study. No target organ was identified at necropsy.

Under the conditions of this test, the acute dermal LD0 for n-butyl methacrylate was greater than 2000 mg/kg of body weight.