Registration Dossier

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Isobutyl acrylate
EC Number:
203-417-8
EC Name:
Isobutyl acrylate
Cas Number:
106-63-8
Molecular formula:
C7H12O2
IUPAC Name:
2-methylpropyl prop-2-enoate
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Lot No. S8003-01-6A

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc., Michigan
- Age at study initiation: approx. 15 weeks
- Weight at study initiation: 2,3 - 2,5 kg
- Housing: individually (stainless steel cages)
- Diet (e.g. ad libitum): measured amount (High Fiber Rabbit Diet 7015 (Harlan Teklad)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test material was applied to the test site in a thin uniform layer which was approximately 0.03 g/cm². The area of application (approximately 180 cm²) was covered with a 4-ply 9.5-cm x 19-cm gauze patch secured with paper tape and overwrapped with Saran Wrap® and Elastoplast® tape to provide an occlusive dressing.
Duration of exposure:
24 h
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
- Other examinations performed: clinical signs, body weight,organ weights, pathology
Statistics:
No statistical evaluation.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
Three males and all five females exhibited weight losses of 27 to 129 g during the first week of the study. Some recovery from these weight losses were noted during the second week of the study although one additional male exhibited a 25 g weight loss from Day 7 to Day 14.
Body weight:
Clinical signs of toxicity in three male and all five females included hypoactivity, staggered gait, injected iris, and/or decreased food consumption. All animals returned to a normal appearance by Day 4 after treatment.
Gross pathology:
At necropsy, the treated skin of each animal was observed to be thickened, diffusely dark red, or had multiple, dark red, eroded areas of variable size. The subcutis of the treated skin in some animals was also observed to have dark red areas of variable size. These observations were indicative of irritation caused by the test material. There were no other visible lesions in any of the animals.
Other findings:
Dermal irritation (based on the most severe score for each animal at any time point) consisted of severe erythema and edema, marked atonia, slight desquamation, marked coriaceousness, and slight to moderate fissuring. Subcutaneous hemorrhaging, blanching, eschar, and possible necrotic areas were also observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The estimated dermal LD50 values for male and female rabbits were determined to be greater than 2,000 mg/kg.
Executive summary:

Isobutyl Acrylate, was evaluated for its acute dermal toxicity potential in male and female rabbits of the Hra:(NZW)SPF strain when administered as a single topical application at a level of 2,000 mg/kg of body weight. No mortality was observed during the study. The estimated dermal LD50 values for male and female rabbits were determined to be greater than 2,000 mg/kg. Clinical signs of toxicity included hypoactivity, staggered gait, decreased food consumption, and injected iris, all of which were transient in nature. All animals returned to a normal appearance by Day 4 after treatment. Body weight losses from 27 to 129 g were observed in three males and all five females during the first week. Some recovery from these weight losses were noted during the second week with the exception that one additional male exhibited a 25 g weight loss from Day 7 to Day 14. The test material produced severe dermal irritation which was probably associated with the observed weight losses. At necropsy, the treated skin of each animal was observed to be thickened, diffusely dark red, or had multiple, dark red, eroded areas of variable size. The subcutis of the treated skin in some animals was also observed to have dark red areas of variable size. These observations were indicative of irritation caused by the test material. There were no other visible lesions in any of the animals.