3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate

EC Number:

223-861-6

EC Name:

3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate

Cas Number:

4098-71-9

Molecular formula:

C12H18N2O2

IUPAC Name:

5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane

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 or test system and environmental conditions:

TEST ANIMALS:
- Source: Winkelmann, Paderborn (Germany)
- Weight at study initiation: 110-140 g
- diet: Ssniff Intermast; Diet deprived 16 hours before oral application of test substance
- Water ad libitum

ENVIRONMENTAL CONDITIONS:
- Room temperature 22°C;
- Air humidity 45-55%;
- Light 12 hours per day

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:

other: decrease in activity, diarrhea, piloerection, in higher  dose groups also tremor (beginning 20 min after dosing, lasting 24 hours) - .

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, disturbances of coordination, diarrhoea, 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. Subsequently the surviving animals showed normal behaviour again throughout the observation period. 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.