Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-11-25 to 1985-12-09
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 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate homopolymer, uretdione type
EC Number:
938-351-5
Molecular formula:
residual C12H18N2O2, otherwise C24H36N4O4 (dimer) and higher species
IUPAC Name:
3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate homopolymer, uretdione type
Details on test material:
Isophorone diisocyanate oligomer (uretdione type) of Hüls AG

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: 5 males mean 181 g, 5 females mean 178 g
- Controls: no
Environmental conditions: - Feed: R 10 complete feed for rats (Ssniff, Soest; Germany)
- Water: tap water ad libitum
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%)
- Air change: 15 times per hour
- Illumination: 12 hour light/dark rhythm

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil
Details on oral exposure:
ADMINISTRATION: 
- Doses per time period: single dose (gavage)
- Volume administered or concentration: 20 ml/kg bw
- Post dose observation period: 14 days
Doses:
10 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
EXAMINATIONS:
- 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)
Statistics:
not required

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
MORTALITY: No deaths
Clinical signs:
CLINICAL SIGNS: 
- 30-60 minutes after dosing: slightly ruffled fur, restlessness
- 2-5 hours after dosing: additionally crouched posture, diuresis and  diarrhea
- 24 hours after dosing: ruffled fur and diuresis
- 48 hours after dosing: no more signs of toxicity
Body weight:
Body weight gain was not affected.
Gross pathology:
NECROPSY FINDINGS: partial hyperemia of small intestine mucosa (4  animals), additionally congestion spleen (1 animal); slight hyperemia of  
gastric mucosa (1 animal)
Other findings:
no other findings

Any other information on results incl. tables

no other information

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the acute toxicity of isophorone diisocyanate cyclodimer in Wistar rats was established to exceed
10 000 mg/kg bw.
Executive summary:

The acute oral toxicity study of isophorone diisocyanate cyclodimer was determined with 5 male and 5 female WISTAR rats. Both male and female rats were treated with 10 000 mg/kg bw. Animals were observed for symptoms of clinical toxicity and mortality for 14 days after treatment. The treated animals showed slightly ruffled fur and restlessness 30-60 minutes after dosing,  2-5 hours after dosing additionally crouched posture, diuresis and  diarrhea. 24 hours after dosing the rats revealed ruffled fur and diuresis. 48 hours after dosing all rats were free of symptoms. No mortality occured, no apparent changes were found in body weight.

Dissection at the end of the experiment revealed partial hyperemia of small intestine mucosa (4  animals),  additionally congestion spleen (1 animal) and slight hyperemia of  gastric mucosa (1 animal).

Therefore the oral LD50 value of isophorone diisocyanate cyclodimer in Wistar rats was established to exceed 10 000 mg/kg bw.