Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: the study was conducted with a method similar to the recognised guidelines. TDI, isomer ratio and purity not specified. No GLP.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1964
Report date:
1964
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.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
m-tolylidene diisocyanate
EC Number:
247-722-4
EC Name:
m-tolylidene diisocyanate
Cas Number:
26471-62-5
IUPAC Name:
2,4-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:
Animals weighing from 2215 to 3180 grams
TEST ANIMALS
- Source: no data available
- Age at study initiation: no data available
- Weight at study initiation: no data available
- Fasting period before study: no data available
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data available


ENVIRONMENTAL CONDITIONS: no data available

IN-LIFE DATES: no data available

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
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. Animals' backs were covered with non-occlusive dressing and confined for 24 hours. At the end of the 24-hr period, the back of each rabbit was washed and the area of compound application examined for evidence of
irritation. 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 performed on each animal at termination.
Duration of exposure:
24 hours
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
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 9 400 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
All animals appeared essentially normal throughout the 14-day observation period.
Body weight:
All animals showed either a body weight gain, or maintained body weight during the study, with the exception of 2 showing a slight weight loss
unrelated to application of the test substance.
Gross pathology:
All animals at all dosage levels were considered essentially normal at necropsy examination. Potential target organs: None observed. No apparent
difference between the sexes.
Other findings:
- Other observations: Dermal irritation was seen at each of the four dosage levels. Peak irritation occurred between the 5th and 10th days following 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:
not classified
Remarks:
Migrated information
Executive summary:

In an acute dermal toxicity study (Wazeter, 1964), groups of albino rabbits (2/sex) were dermally exposed to Toluene Diisocyanate for 24h at doses of 2500 -9400 mg/kg bw. Tested substance was applied to intact and abraded skin. Animals then were observed for 14 days. All rabbits survived the course of study. The application of Toluene Diisocyanate resulted in delayed dermal irritation but all skin lesions subsided by the 14th day of observation. At necropsy examination, all animals were considered as being essentially normal. Dermal LD50 is > 9400 mg/kg bw.