m-tolylidene diisocyanate

Acute Toxicity: dermal

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:

guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1964

Report date:

1964

Reference 2

Reference Type:

publication

Title:

Toxicology, industrial hygiene and medical control of TDI, MDI and PMPPI

Author:

Woolrich PF

Year:

1982

Bibliographic source:

Am. Ind. Hyg. Assoc. J. 43 (2): 89-97

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Two rabbits/sex instead of 5 were tested per group. The skin of half the rabbits in each group was abraded by producing shallow incisions with a scalpel blade.TDI isomer ratio and purity not specified.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

m-tolylidene diisocyanate

EC Number:

247-722-4

EC Name:

m-tolylidene diisocyanate

Cas Number:

26471-62-5

Molecular formula:

C9H6N2O2

IUPAC Name:

2,4-diisocyanato-1-methylbenzene, 2,6-diisocyanato-1-methylbenzene

Details on test material:

- Name of test material (as cited in study report): Toluene diisocyanate
- Physical state: clear slightly viscous oily liquid
- Analytical purity: considered to be free of impurities

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2215 - 3180 g
- Housing: individually in metal cages
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ~ 3 inches²
- Type of wrap if used: non-occlusive dressing

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

TEST MATERIAL
- Amounts applied: doses of 2500 - 9400 mg/kg

OTHER
TDI applied undiluted to intact or abraded skin of 2 male and 2 female rabbits at doses of 2500 - 9400 mg/kg. The dorsal skin of each rabbit was prepared for treatment by close clipping of the hair with an electric clipper. In addition, the skin of half the rabbits in each group was abraded by producing shallow incisions with a scalpel blade over an area approximately three inches square. The compound was applied to each individual animals in the liquid form as received and administered on a volume basis. The animals were observed daily for a total of 14 days for pharmacotoxic signs and dermal irritation. Body weights were obtained for each animal and a complete necropsy was performed on each animal at termination.

Duration of exposure:

24 h

Doses:

2500, 3900, 6000, and 9400 mg/kg bw

No. of animals per sex per dose:

Four groups of 4 rabbits (2/sex) were used.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (1) and weighing (2):
(1) Observations occured daily
(2) weighing occured at the beginning and at the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: Signs of dermal irritation

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 9 400 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: All animals appeared essentially normal throughout the 14-day observation period.

Gross pathology:

All animals at all dosage levels were considered essentially normal at necropsy examination. No potential target organs were observed. No apparent difference between the sexes was observed.

Other findings:

- Other observations: Dermal irritation was seen at each of the four dosage levels. Peak irritation occurred between the 5th and 10th day after application. During this time, erythema, edema, atonia, and coriaceousness were observed in most cases to a moderate-to-marked degree. From the 8th to the 14th day, moderate-to-marked desquamation and fissuring were observed. This condition subsided by the termination of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met