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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:
1985-02-04 to 1985-02-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

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)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of 2,2,4-trimethylhexa-1,6-diyl diisocyanate and 2,4,4-trimethylhexa-1,6-diyl diisocyanate
EC Number:
915-277-1
Cas Number:
32052-51-0
Molecular formula:
C11H18N2O2
IUPAC Name:
Reaction mass of 2,2,4-trimethylhexa-1,6-diyl diisocyanate and 2,4,4-trimethylhexa-1,6-diyl diisocyanate
Test material form:
other: liquid
Details on test material:
2,2,4-/2,4,4-trimethylhexane-1,6-diisocyanate of Hüls AG, purity > 99.0 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ORGANISMS: 
- Strain: Bor: WISW (SPF TNO)
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation: males mean 259 g, females mean 199 g
- Controls: no
Housing conditions:
- Room temperature 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%)
- Light: 12h per day
- Air exchange: 15-fold per hour
- Access to water: ad libitum
- Diet: R10 diet for rats (Ssniff, Soest)

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: no vehicle
Details on dermal exposure:
ADMINISTRATION: 
- Area covered: dorsal skin (shaved 24 hours in advance)
- Occlusion: mull patch, elastic dressing (for 24 hours)
- Removal of test substance: after patch removal, washing with warm water  and swabbing with cellulose

Duration of exposure:
24 h, removal of test substance: after patch removal, washing with warm water  and swabbing with cellulose
Doses:
7000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
EXAMINATIONS: 
- Post dose observation period: 14 days
- Body weights: before, and 1, 7, 14 days post dosing
- Clinical signs and mortality: within 6 hours after dosing, thereafter  daily
- Necropsy: all animals (macroscopic), no further details
Statistics:
not required

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 000 mg/kg bw
Mortality:
MORTALITY: No deaths occurred
Clinical signs:
CLINICAL SIGNS: Immediately after treatment, animals showed intense  defense reactions and vocalization, piloerection, agitation, and took a  
stretched (caused by patch), mostly abdominal position. After 24 hours  (patch removal), the skin of the application area showed slight erythema  and severe edema. After 2 days, it showed a brown discoloration and  slight induration. Piloerection was still present, and hypothermia and  slowed down motions were observed in one animal. Except for the local  effects, the animals were free from symptoms after four days. By the end  of the study, the application area showed incrustation and scar  formation. 
Body weight:
Body weight development was transiently inhibited.
Gross pathology:
NECROPSY FINDINGS: Hyperemia in the mucosa of stomach and small  intestine, in peritoneum and diaphragm; mottling on livers and kidneys;  fusion of abdominal organs.
Other findings:
no other findings

Any other information on results incl. tables

no further results

Applicant's summary and conclusion

Conclusions:
In a determination of the acute dermal toxicity on male and female rats it was found that the LD50 of the test item 2,2,4(2,4,4)-trimethylhexa-
methylenediisocyanate is greater than 7000 mg/kg of body weight.
Executive summary:

A test performed according to OECD TG 402 with male and female rats (Hüls AG, 1985) demonstrated the low acute dermal toxicity of 2,2,4(2,4,4)-trimethylhexamethylenediisocyanate. No animal (= 0/10) died after 24 hours occlusive application of 7000 mg/kg.   Immediately after treatment, animals showed intense  defense reactions and vocalization,  piloerection, agitation, and took a  stretched (caused by patch), mostly abdominal position. After 24 hours (patch removal),  the skin of the application area  showed slight erythema  and severe edema. After 2 days,  it showed a brown discoloration and  slight induration. Piloerection  was still present, and hypothermia and  slowed down motions were observed in one animal. Except for the local  effects, the animals were free from symptoms after four days. By the end  of the study,  the application area showed incrustation and scar  formation.