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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Act, September 27, 1973.
Deviations:
not specified
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methylstyrene
EC Number:
210-762-8
EC Name:
4-methylstyrene
Cas Number:
622-97-9
Molecular formula:
C9H10
IUPAC Name:
1-methyl-4-vinylbenzene
Test material form:
liquid
Details on test material:
- Name as cited in study report: MCTR-243-77

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test animals:
- Weight at study initiation: 2.10 to 2.50 kg
- Housing: Not specified (each animal was restrained in a harness during the 24 h application period)

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Removal of the test substance
- Washing: Using a damp towel
- Time after start of exposure: 24 h
- Amount(s) applied: 0.5, 1.0, 2.0, 4.0 or 5.0 mL/kg
- Concentration: Undiluted
- For solids, paste formed: Not applicable
Duration of exposure:
24 hours
Doses:
Group 1: 0.5 mL/kg bw (total volume given: 1.1 mL)
Group 2: 1.0 mL/kg bw (total volume given: 2.2 - 2.3 mL)
Group 3: 2.0 mL/kg bw (total volume given: 4.3 - 4.5 mL)
Group 4: 4.0 mL/kg bw (total volume given: 8.4 - 9.0 mL)
Group 5: 5.0 mL/kg bw (total volume given: 11.0 - 12.5 mL)
No. of animals per sex per dose:
2 males and 2 females
Control animals:
no
Details on study design:
The skin of one male and one female in each group was abraded, while the skin of the remaining male and female was left un-abraded. The test substance was applied to the site and remained in contact with the skin for 24 h, during which time each animal was restrained in a harness. An occlusive wrap was not used (the dental dam routinely used for this purpose was found to be incompatible with the test substance). After the 24 h application period, each animal was removed from its harness and the unabsorbed test substance was removed using a damp towel. All animals were observed for signs of dermal irritation, gross signs of systemic toxicity indicative of percutaneous absorption, and mortality, once daily for the following 14 days. At the end of the observation period, all animals were weighed, killed and a macroscopic examination was performed at necropsy.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
Based on a relative density of 0.917, this is equivalent to an LD50 of 4585 mg/kg bw
Mortality:
There were no mortalities.
Clinical signs:
There were no signs of systemic toxicity or behavioral changes. At the site of test substance application, the following findings were noted: slight to moderate erythema and very slight to slight edema were noted in Groups 1, 2, 3 and 4, with moderate responses occurring in Group 5. These findings returned to normal during the second week of the observation period, except in Group 5 where they persisted throughout the observation period. Slight fissuring was noted occasionally in two animals in Group 1 and one animal in Group 2, and (this finding) was classified as being slight to moderate in Group 5. A dose-related incidence of coriaceous skin was noted in most animals, with slight responses in Groups 1, 2, 3 and 4 which returned to normal by the end of the observation period. Moderate responses of coriaceous skin were noted in Group 5. In addition, atonia and desquamation were noted in Group 5.
Body weight:
There was no indication of an adverse effect on body weight.
Gross pathology:
There were no remarkable macroscopic findings at necropsy.

Applicant's summary and conclusion

Conclusions:
Under the study conditions, the dermal LD50 was determined to be >5.0 mL/kg bw. Based on a relative density of 0.917, this is equivalent to an LD50 of 4585 mg/kg bw.
Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance according to Federal Hazardous Substances Act, September 27, 1973. Five groups of 2 male and 2 female rabbits were given a single non-occluded 24 h application of the test substance at 0.5, 1.0, 2.0, 4.0 or 5.0 mL/kg bw. The skin of two rabbits per group was abraded while the skin of remaining two rabbits was left intact. After 24 h, residual test substance was removed and the animals were observed for a further 14 d. Mortality and clinical signs were recorded daily, including examination for signs of skin irritation and systemic toxicity. Body weights were determined on Day 0 (day of application) and on Day 14, prior to necropsy. At necropsy, a macroscopic examination was performed. No mortality occurred in any of the rabbits during the study and no signs of systemic toxicity or behavioral changes were noted. At the site of test substance application, the following findings were noted: slight to moderate erythema and very slight to slight edema in all groups. These findings returned to normal during the second week of the observation period, except in Group 5. Slight fissuring was noted occasionally in two animals in Group 1 and one animal in Group 2. This finding was classified as being slight to moderate in Group 5. A dose-related incidence of coriaceous skin was noted in most animals, with slight responses in Groups 1, 2, 3 and 4 which returned to normal by the end of the observation period. Moderate responses of coriaceous skin were noted in Group 5. In addition, atonia and desquamation were noted in Group 5. Under the study conditions, the dermal LD50 was determined to be >5.0 mL/kg bw. Based on a relative density of 0.917, this is equivalent to an LD50 of 4585 mg/kg bw ( Adamik, 1997).