1,3-bis(1-isocyanato-1-methylethyl)benzene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 5, 1981 to May 21, 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3-bis(1-isocyanato-1-methylethyl)benzene

EC Number:

220-474-4

EC Name:

1,3-bis(1-isocyanato-1-methylethyl)benzene

Cas Number:

2778-42-9

Molecular formula:

C14H16N2O2

IUPAC Name:

1,3-bis(1-isocyanato-1-methylethyl)benzene

Details on test material:

- Name of test material (as cited in study report): 85,772
- Lot/batch No.: S-13708-76

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Hewitt, N.J.
- Housing: Stainless steel cages with wire mesh bottoms
- Diet: Certified Rabbit Chow #5322 (Ralston Purina Company), ad libitum
- Water: Potable water, ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 h fluorescent light/12 h dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal surface (back)
- Type of wrap if used: Occlusive wrap secured by bandaging and elastic tape


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2,000 mg/kg bw
- Concentration (if solution): Undiluted
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2,000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed twice daily for general condition, behavior, and signs of toxicity; Body weights were recorded on Days -1, 0, 1, 2, 3, 6, 10 and 14
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs and body weight

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

One death occurred on Day 4

Clinical signs:

- Dermal irritation at the abraded sites; mean score of 3.9, maximal score on Day 14 with eschar formation
- No signs of systemic toxicity

Body weight:

No remarkable changes in the body weights

Gross pathology:

No significant pathological changes

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the test conditions, acute dermal LD50 of the test material in rabbits was determined to be > 2,000 mg/kg bw.

Executive summary:

A study was conducted to evaluate acute dermal toxicity of the test substance in rabbits. The study was performed according to a method similar or equivalent to OECD Guideline 402. The substance (2,000 mg/kg bw) was applied topically to the abraded skin of 5 male and female young adult rabbits via 24 h occlusive patches. All animals were observed twice daily throughout the 15 day study and all surviving animals were sacrificed. A gross post-mortem examination was performed and samples of the treated skin were retained. One death occurred on Day 4 but no specific signs of systemic toxicity were observed. Dermal irritation occurred at the abraded sites with mean score (Draize score) of 3.9 and maximal score observed on Day 14 with eschar formation. Under the study conditions, the acute dermal LD50 of the test substance in rabbits was determined to be >2,000 mg/kg bw (Chow, 1981).