4,4'-methylenediphenyldiisocyanate and 2,4'-diisocyanatodiphenylmethane and their oligomerisation reaction products with 2,2'-oxydiethanol, propane-1,2-diol and butane-1,3-diol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented study report which meets basic scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1964

Report date:

1964

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Full details not in report. Numbers per dose = 2 and doses above limit dose used.

Principles of method if other than guideline:

Pre guideline study nevertheless fullfills the modern requirements.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

9016-87-9

Cas Number:

9016-87-9

IUPAC Name:

9016-87-9

Constituent 2

Reference substance name:

Isocyanic acid, polymethylenepolyphenylene ester

IUPAC Name:

Isocyanic acid, polymethylenepolyphenylene ester

Details on test material:

- Name of test material (as cited in study report): Polymethylene Polyphenylisocyanate (PAPI)
- Physical state: dark, viscous, oily liquid
- Analytical purity: pure, no further information

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean body weight at study initiation: 2215-3180 g
- Housing: single
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 3 inch2 (19.35 cm2) in case of abraded skin
- Preparation of test site: The dorsal skin was prepared for treatment by closely clipping of the hair with an electric clipper in 2 rabbits (1 male and 1 female) per group. In addition, the skin of the rest of 2 rabbits per group was abraded by producing shallow incisions with a scalpel blade. The animals were confined in immobilising holders for 24 hours with their backs covered in rubberised cloth.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm water
- Time after start of exposure: 24 hr

Duration of exposure:

24 hr

Doses:

2500, 3900, 6000 and 9400 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed daily for clinical signs and dermal irritation. Body weights were obtained for each animal at the end of the experiment.
- Necropsy of survivors performed: yes. All animals were sacrificed with air embolization.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 9 400 mg/kg bw

Mortality:

No mortalities were observed.

Clinical signs:

other: All the animals appeared normal throughout the 14 days observation period with the exception of dermal irritation.

Gross pathology:

No substance- related abnormalities were observed. Sub-endocardial haemorrhages, apparently dose related observed were of questionable significance due to sacrifice of animals by air embolisation.

Other findings:

Dermal irritation: The irritation noted was slight in all instances. The slight erytherma produced initially at all dosage levels was negative after seven
days. All animals at all dosage levels did exhibit a slight coriaceousness which in most instances continued throughout the 14-day observation period. Transient atonia was observed in a few animals at the three high dosage levels; however, this again was slight in nature. One animal at the highest dosage level exhibited slight edema during the first and second days of the study. There was no desquamation nor fissuring noted with this
compound.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU