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Toxicological information

Acute Toxicity: dermal

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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

Constituent 1
Chemical structure
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)
Details on test material:
4,4'-methylenedicyclohexyl diisocyanate, purity > 99.3 %

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: Approximately 30 minutes after treatment animals showed restlessness and tried to remove dressings. Later on animals adopted a stretched position, and transiently vocalization, piloerection and Straub reaction was observed. 24 hours after removal of dress
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.