4,4'-methylenedicyclohexyl diisocyanate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan - Feb 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

e.g. non-GLP, test material (classified as Skin Irrit. Cat. 2) was applied undiluted

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)

Version / remarks:

(1981)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-methylenedicyclohexyl diisocyanate

EC Number:

225-863-2

EC Name:

4,4'-methylenedicyclohexyl diisocyanate

Cas Number:

5124-30-1

Molecular formula:

C15H22N2O2

IUPAC Name:

1,1'-methylenebis(4-isocyanatocyclohexane)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Bor: WISW (SPF TNO)
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation (mean): males 240 g, females 211 g
- Housing: singly in Makrolon type III cages
- Diet and 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:

other: covered with a mull patch, wrapped with an elastic bandage, fixed with Leukoflex

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The application area was shorn 24 hours before administration.
- Type of wrap if used: The application area was covered with a mull patch (7x5 cm), wrapped with an elastic bandage and fixed with Leukoflex for 24 hours.
- Removal of test substance: Treated areas were washed with warm water after removal of the dressings.

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:

For dose finding a pretest was performed in advance. No details reported.

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for effects during the first 6 hours after treatment and then daily in the further course of the study. Onset, type and duration of any clinical sign and onset of mortalities were recorded.
- Frequency of weighing: before application, and 1, 7, and 14 days thereafter
- Necropsy of survivors performed: yes

Statistics:

The statistical means of body weights were calculated. The LD50 was determined according to Litchfield and Wilcoxon (J. Pharmacol. Exp. Ther. 96, 1949, 99).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Mortality:

Mortalities were not observed.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Body weight gain was transiently decreased.

Gross pathology:

At necropsy 7 animals showed partial hyperemia of the small intestine mucosa and 3 animals strong hyperemia of the forestomach mucosa. Additionally for one animal partly thickening of the forestomach mucosa was noted.

Applicant's summary and conclusion

Executive summary:

An acute dermal toxicity study was conducted according to OECD TG 402 with 5 male and female rats per dose group. In that study the animals were once exposed for 24 hours to the undiluted test substance at a limit dose of 7000 mg/kg. The animals were observed for mortality, body weight gain and clinical signs for a period of 14 days. Gross necropsy was performed at termination of study.

Mortalities were not observed in the course of the study. Body weight gain was transiently decreased. The treated skin areas exhibited signs of irritation (erythema, oedema, scab formation). Gross necropsy findings, i.e. partial hyperemia of the small intestine mucosa, strong hyperemia of the forestomach mucosa and in one animal thickening of the forestomach mucosa also indicated irritant properties of the substance.

The LD50 was concluded to be > 7000 mg/kg bw.