3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate homopolymer, isocyanurate type

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-02-15 - 1195-03-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study; GLP study without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: 92/69/EEC

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: TSCA § 798.1150 (1989)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: 93/21/EEC

Deviations:

no

GLP compliance:

yes

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, oligomers

EC Number:

500-125-5

EC Name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers

Cas Number:

53880-05-0

Molecular formula:

residual C12H18N2O2, otherwise C36H54N6O6 (trimer) and higher species

IUPAC Name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate homopolymer

Constituent 2

Reference substance name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate homopolymer, isocyanurate type

EC Number:

931-312-3

Cas Number:

53880-05-0

Molecular formula:

residual C12H18N2O2, otherwise C36H54N6O6 (trimer) and higher species

IUPAC Name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate homopolymer, isocyanurate type

Details on test material:

Test substance of Hüls AG, Batch 0894 no. 3193
ca. 0.3 % isophorone diisocyanate monomer, 50-60 % trimer, 40-50 % pentamer and higher oligomers

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Strain: Hsd Cpb:WU (formerly BOR:WISW (SPF-Cpb))
- Source: Harlan Winkelmann GmbH, Borchen (Germany)
- Age: 2-3 months
- Weight at study initiation: males 190-207 g, females 173-193 g
- Number of animals: 5 per concentration and sex
- Controls: conditioned air

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

other: directed-flow nose-only inhalation

Vehicle:

other: compressed air

Details on inhalation exposure:

- Particle size:    
489 mg/m3: MMAD ca. 1.9 µm, GSD ca. 1.8, relative mass < 3 µm ca. 70 %   
2830 mg/m3: MMAD ca. 3.4 µm, GSD ca. 1.7, relative mass < 3 µm ca. 42 %   
5010 mg/m3: MMAD ca. 3.5 µm, GSD ca. 1.7, relative mass < 3 µm ca. 39 %

- Type or preparation of particles: micronization followed by 489 mg/m3: Wright-Dust-Feeder followed by cyclone   
higher concentrations: Exactomat 4200
- Concentration monitoring: samples from breathing zone to  cellulose-acetate filter, gravimetric evaluation
- Particle size determination: samples from breathing zone to cascade  impactors

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

489; 2830; 5010 mg/m3

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Post dose observation period: 2 weeks

EXAMINATIONS:  - body weights: before exposure, days 3 and 7, weekly thereafter
- clinical signs and mortality: several times on day of exposure, twice  (weekends: once) daily thereafter, including: changes in skin and fur;  
eyes; mucous membranes; respiratory, circulatory, autonomic and central  nervous system; somatomotor activity and behavior pattern; Functional  Observational Battery; rectal temperatures.
- necropsy: all animals (macroscopic)

Statistics:

With graphs of means of data, the indicated parameters were evaluated relative to controls (mean = 100 %). The single standard deviations are also
shown relative to the means of the controls. Statistically significant differences (versus control) are indicated by asterisks ('*' for p <0.05 and '**' for
p<0.01).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 010 mg/m³ air

Exp. duration:

4 h

Remarks on result:

other: No deaths occurred.

Mortality:

No deaths occurred.

Clinical signs:

other: Concentration-dependent signs pertinent to mild  respiratory tract irritation (bradypnea, labored breathing pattern,  serous discharge from the nose, hypothermia); secondary nonspecific signs  (motility reduced, ungroomed hair-coat, piloerection).  All si

Body weight:

Body weight gain was transiently decreased in the 5010 mg/m3 group.

Gross pathology:

No evidence of macroscopically discernible organ  changes was found. A slightly increased number of red foci on the lungs had no clear 
concentration-dependence and was considered to be of no  toxicological relevance.

Other findings:

No other treatment related effects were observed within this study.

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Conclusions:

The aerosolized test substance (dust) proved to have no significant acute inhalation toxicity to rats. The clinical observations demonstrate that the
dust acts as mild respiratory tract irritant.

Executive summary:

The study on the acute inhalation toxicity of IPDI homopolymer in rats has been conducted in accordance with OECD Guideline No. 403. Ten male and ten female rats were exposed to a solid aerosol (dust) average concentration of 489, 2830, and 5010 mg/m³ air. Attempts were made so that aerosol generated was respirable to rats. The animals were observed for 14 days after application. The LC₅₀ (inhal., aerosol, 4 hr) in rats (male, female) value was estimated to be > 5010 mg/m³.

Aerosol (dust) concentrations up to and including 5010 mg/m³ did not induce test substance related mortality. In all groups exposed to the test compound concentration-dependent signs pertinent to mild respiratory tract irritation (bradypnea, laboured breathing pattern, serous discharge from nose, hypothermia) as well as secondary nonspecific signs (motility reduced, ungroomed hair-coat, piloerection) were observed. The body weight gain was decreased in the 5010 mg/m³ group. All signs were transient in nature and disappeared within the first 3 postexposure days.