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EC number: 223-861-6 | CAS number: 4098-71-9
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- Ecotoxicological Summary
- Aquatic toxicity
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- Short-term toxicity to fish
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- Toxicological Summary
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- Additional toxicological data

Respiratory sensitisation
Administrative data
- Endpoint:
- respiratory sensitisation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1994-01-31 to 1994-03-04
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: exposure criteria of OECD Guideline 403 (1981) and Directive 84/449/EEC, B.6 fulfilled
- Deviations:
- not applicable
- Principles of method if other than guideline:
- exposure criteria of OECD Guideline 403 (1981) and Directive 84/449/EEC, B.6 fulfilled
Pauluhn J and Eben A (1991). Validation of a non-invasive technique to assess immediate- or delayed-onset of airway hyperreactivity in guinea-pigs.
J. Appl. Toxicol. 11, 423-431; Pauluhn J (1994). Validation of an improved nose-only exposure system for rodents. J. Appl. Toxicol. 14, 55-62. - GLP compliance:
- yes
Test material
- 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 Bayer AG, Batch No. 1.5 / 3-20, purity > 99 %
Constituent 1
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Strain: Hartley [Crl:(HA)BR]
- Sex: female
- Source: Charles River Wiga, Sulzbach (Germany)
- Age: ca. 2 months
- Weight at study initiation: 237-273 g; mean 256 g
- pre-experimental treatment of animals and animal housing: animals were acclimatized for at least 5 days before use; before start of experiment health status of each animal was assessed; animals were assigned to exposure gruops at random;
- diet: Altromin 3022 (Altromin GmbH, Lage)
- tap-water ad libitum
ENVIRONMENTAL CONDITIONS:
- room temperature: 22 °C (+/- 2°C)
- humidity: appr. 50%
- dark/light: 12h/12h (14 watt/m2)
- air-exchange: appr. 10-fold/h
Test system
- Route of induction exposure:
- intradermal
- Route of challenge exposure:
- other: nose only inhalation of aerosol
- Vehicle:
- other: corn oil
- Concentration:
- first day: 10.2 mg/m3 test substance 30 min nose-only
second day: 0.05; 0.15; 0.5 % Acetylcholine for 15 min each
last day: 35.5 mg/m3 conjugate of test substance with guinea pig serum albumin - No. of animals per dose:
- 8 treated
8 vehicle (control) - Details on study design:
- 1st application: Induction 0.1 % intracutaneous
2nd application: Challenge other: nose only inhalation of aerosol
ADMINISTRATION/EXPOSURE
- Induction schedule: days 0, 2, 4 (100 ul each)
- Challenge schedule: 4 subgroups, 4 animals each
days 21/22/28 (control subgroup a)
days 22/23/29 (treated subgroup a)
days 23/24/30 (control subgroup b)
days 24/25/31 (treated subgroup b)
- Concentrations used for challenge:
first day: 10.2 mg/m3 test substance 30 min nose-only
second day: 0.05; 0.15; 0.5 % Acetylcholine for 15 min each
last day: 35.5 mg/m3 conjugate of test substance with guinea pig serum albumin
EXAMINATIONS
- During sacrifice the trachea, lung and lung associated lymph nodes were fixed and subjected to histopathological evaluation. Lung weights were also determined - Pilot study: assessment of the approximate irritant threshold concentration - Challenge controls:
- Validity of this animal model was assessed with the known human sensitizer Trimellitic Anhydride. Additional ACh challenge was performed to enhance identification of and distinction between specific as well as non specific airway hyperresponsiveness.
- Positive control substance(s):
- trimellitic anhydride (TMA)
- Negative control substance(s):
- other: vehicle (corn oil)
Results and discussion
- Results:
- RESULTS OF PILOT STUDY: see test concentration RESULTS OF TEST - Sensitization reaction: High titer IgG1 antibody observed proved that successful sensitization had occurred. However,
when challenged, the incidence of immediate-onset respiratory reactions was roughly the same in all groups. No delayed-onset
reactions, deaths or anaphylactic reactions were observed. Challenge with acetylcholine did not evoke group specific respiratory
responses. - Clinical signs: No clinical signs or specific abnormalities were observed at necropsy. - Positive control results:
- Severe reactions were observed with trimellitic anhydride (CAS RN 552-30-7) when investigated with the current animal model,
using the same induction and challenged. - Negative control results:
- no relevant reactions observed
Any other information on results incl. tables
no further remarks
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study the test item did not induce respiratory sensitization in guinea-pigs.
- Executive summary:
Respiratory tract sensitization of guinea pigs following intradermal induction (1%, 100 µl) was examined in this study in accordance with the exposure criteria defined in OECD TG 403. High titer IgG1 antibody observed proved that successful sensitization had occurred. However, when challenged by nose only inhalation of aerosol at varying concentrations, the incidence of immediate-onset respiratory reactions was roughly the same in all groups. No delayed-onset reactions, deaths or anaphylactic reactions were observed. Challenge with acetylcholine did not show specific respiratory responses indicating that the animals were hyperrespondive to cholinergic acetylcholine stimuli. Severe reactions were observed with trimellitic anhydride (CAS No. 552-30-7) when investigated with the current animal model, using the equivalent induction and challenge. Under the conditions of this study the test item did not induce respiratory sensitization in guinea-pigs.
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