Hexamethylene 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:

other: guideline study with acceptable restrictions; kind of limit test with unusual dose, no rationale for dose selection reported

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethylene diisocyanate

EC Number:

212-485-8

EC Name:

Hexamethylene diisocyanate

Cas Number:

822-06-0

Molecular formula:

C8H12N2O2

IUPAC Name:

1,6-diisocyanatohexane

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann (Borchen, Germany)
- Age at study initiation: no data
- Mean weight at study initiation: males: 242 g; females: 206 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 5x7 cm
- % coverage: not specified
- Type of wrap if used: mull patch, elastic dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not specified

Duration of exposure:

24 hours

Doses:

7000 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
- Frequency of observations and weighing: for 6 hours on day of exposure, daily thereafter (clinical signs); before exposure and on days 1, 7 and 14 after treatment (body weights)
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

LD50 values were calculated according to the method of Litchfield and Wilcoxon (J. Pharmacol. exper. Therap. 96: 99, 1949).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Mortality:

All 10 animals survived the treatment.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Body weight gain was transiently inhibited.

Gross pathology:

Hyperemia and swelling of the gastric mucosa (all animals); distinct hyperemia of the of small intestine mucosa, peritoneum, pleura, diaphragm and pancreas (all animals); pale spots on kidney (3 animals); dark spots on liver (2 animals).

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information

Executive summary:

The acute dermal toxicity of Hexamethylendiisocyanat-1,6 was low with an LD50 value > 7000 mg/kg bw for male and female rats according to OECD TG 402. Single occlusive administration of 7000 mg/kg bw for 24 hours was tolerated without mortalities. The animals showed clinical signs (rough hair, crusts and scars in application area) up to the end of the 14-day observation period. Body weight gain was transiently inhibited. Gross necropsy revealed hyperemia and swelling of the gastric mucosa as well as distinct hyperemia of the of small intestine mucosa, peritoneum, pleura, diaphragm and pancreas in all animals.