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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No data on purity of test substance

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
; if relevant deviations exist they are described under materials and methods or as appropriate entries in this endpoint study record
Principles of method if other than guideline:
Method based on "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the staff of the Division of Pharmacology, FDA (1959), complies with OECD Guideline 401 (1981)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Isophorone diisocyanate of Veba-Chemie AG, Gelsenkirchen (Germany); purity not reported; pH value 5.5

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Winkelmann, Paderborn (Germany)
- Weight at study initiation: 110-140 g
Environmental conditions:
Keeping of animals: diet: Ssniff Intermast;
Water ad libitum;
Room temperature 22°C;
Air humidity 45-55%;
Light 12 hours per day,
Diet deprived 16 hours before oral application of test substance

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Doses: calculated from volume
- Doses per time period: single dose (gavage)
Doses:
4.21; 5.29; 6.67; 8.40; 10.58 g/kg bw
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
no
Details on study design:
- Volume administered or concentration: undiluted test substance, 3.98;  5.00; 6.30; 7.94; 10.00 ml/kg bw   * 1.058g/ml = 4.21; 5.29; 6.67; 8.40; 10.58 g/kg bw
- Post dose observation period: 14 days
EXAMINATIONS: 
central nervous system, lung, heart, heart sac, stomach,  large intestine, small intestine, liver, spleen, kidneys, serosa, lymph  nodes, gonads, perineum
Statistics:
- LD50 calculation: according to Litchfield and Wilcoxon, in connection  with the Gauß integral

Results and discussion

Preliminary study:
not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 814 mg/kg bw
95% CL:
>= 4 295 - <= 5 396
Remarks on result:
other: 95% CL in mg/kg bw
Mortality:
- Time of death: within 3 days
- Number of deaths at each dose 14 days after substance application:    3.98 ml/kg: 2/10 ;  5.00 ml/kg: 8/10 ; 6.30 ml/kg: 10/10; 7.94 ml/kg: 10/10; 10.00 ml/kg: 10/10      
- LD50 (24 hours) = 7.10 ml/kg = 7512 mg/kg   confidence interval: 6.02 - 8.38 ml/kg  
- LD50 (7 days, 14 days) = 4.55 ml/kg = 4814 mg/kg   confidence interval: 4.06 - 5.10 ml/kg
Clinical signs:
decrease in activity, diarrhea, piloerection, in higher  dose groups also tremor (beginning 20 min after dosing, lasting 24 hours) - .
Body weight:
Growth rates returned to normal by the end of the post exposure  observation period
Gross pathology:
NECROPSY FINDINGS: reddening of stomach and intestinal mucosa of dead  animals, loss of hair at perineum of survivors

Any other information on results incl. tables

table of results see under attached background material

Applicant's summary and conclusion

Conclusions:
Treatment related mortality and other sublethal symptoms were observed in rats within the 14 day post-dosing period for the doses used in this acute oral toxicity study. The LD50 (oral) was calculated to be 4814 mg/kg bw in rats. Under the conditions of this study the acute toxicity of test item after oral exposure in rats was very low
Executive summary:

The test item was applied once to 5 dose-groups of rats (5 male and 5 female Wistar rats per dose-group) in doses of 3.98 ml/kg bw; 5.00 ml/kg bw; 6.30 ml/kg bw; 7.94 ml/kg bw and 10.00 ml/kg bw of undiluted test item. The observation period was 14 days. At the highest dose (10.00 ml/kg bw) all animals died within 24 hours after oral application of the test item. Clinical signs were reddening of stomach and intestinal mucosa in dead animals.

In all doses groups a decrease in activity, diarrhea, piloerection, and in higher dose groups (>= 7.94 ml/kg bw) also tremor was observed beginning 20 min after dosing and lasting 24 hours. A loss of hair at perineum was observed among the survivors at the end of the study. According to this study the LD50 value (oral) was determined to be 4814 mg/kg bw in rats for the test item 3-Isocyanatomethyl-3.5.5-trimethylcyclohexyl isocyanate. Therefore under the conditions of this study the acute toxicity of 3-Isocyanatomethyl-3.5.5-trimethylcyclohexyl isocyanate after oral application in rats is very low.