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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-02-04 to 1985-02-18

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions: Kind of limit test with unusual dose, no rationale for dose selection reported

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)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

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 Hüls AG, purity > 99 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS:
- Source: Winkelmann, Borchen (Germany)
- Weight at study initiation: males 265 g, females 208 g (mean)
- 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)
- Randomisation: By reference to an arbitrary number table on distribution into the test cages

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION: 
- Occlusion: yes
- Removal of test substance: with warm water after 24 hours

Duration of exposure:

24 hours

Doses:

7000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXAMINATIONS: 
- Clinical observation and mortality: for 6 hours on day of exposure,  daily thereafter
- Body weights: Before exposure and on days 1, 7 and 14 after treatment
- Gross pathology: After observation period (14 days)
- LD 50 is generally determined according to Litchfield and Wilcoxon

Statistics:

median of body weights were calculated

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Remarks on result:

other: 95% CL not applicable

Mortality:

MORTALITY:  - Number of deaths at each dose: no deaths

Clinical signs:

other: CLINICAL SIGNS: 5/5 females and 5/5 males showed signs of intoxication  for up to 72 hours: After 24 hours most animals showed piloerection,   sedation, ataxia, hypothermia, hunched position, irritations at  application site. 

Gross pathology:

NECROPSY FINDINGS: hyperemia of stomach and intestinal mucosa, pale  kidneys with dark spots, incrustation and cicatrization at application  site 
(number of affected animals not reported)

Other findings:

no further findings

Any other information on results incl. tables

Increase in body weight (means) in g:

• before administartion (fasting): 236.4 g


• 24h after administration: 236.6 g


• 1 week after administration: 230.6 g


• 2 weeks after administration: 248.2 g
   
  
  

Applicant's summary and conclusion

Conclusions:

Sublethal symptoms of intoxication but no treatment related mortality was observed within the 14 day post-dosing period with the dose used in this study. Under the conditions of this acute dermal toxicity test the LD50 (dermal) was calculated to be > 7000 mg/kg bw in male and female rats. Therefore under the conditions of this study the acute toxicity of 3-Isocyanatomethyl-3.5.5-trimethylcyclohexyl isocyanate after dermal application in rats is very low.

Executive summary:

A test performed according to OECD TG 402 with male and female rats (Hüls AG, 1985) demonstrated the low acute dermal toxicity of3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate. The treated animals showed signs of toxicity for up to 72 hours. There was a temporary inhibitive influence on the increase in body weight. Dissection at the end of the experiment showed hyperaemia of the gastric and small intestinal mucosa as well as very pale-coloured kidneys with dark flecks. The application area showed incrustations and scars on the skin. No animal (= 0/10) died after 24 hours occlusive application of 7000 mg/kg. Non-specific transient signs of intoxication (sedation, ataxia) and obvious skin irritation at the application site were observed in all animals.