Registration Dossier
Registration Dossier
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EC number: 223-861-6 | CAS number: 4098-71-9
Immunotoxicity
Administrative data
- Endpoint:
- immunotoxicity
- Remarks:
- other: immunological response to IPDI conjugates
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- not described
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Intradermal or inhalative exposure of animals with IPDI haptene followed by a subcutane challenge with the IPDI conjugate . Blood samples are evaluated for specific antibody classes which may relate to challenge results.
- GLP compliance:
- not specified
- Limit test:
- no
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:
- no details descibed about purity of the test substance
Constituent 1
Test animals
- Species:
- guinea pig
- Strain:
- other: English smooth haired
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Species: guinea pigs
- Strain: English smooth haired
- Sex: female
- Source: Hilltop Lab Animals, Scottdale (PA, USA)
- Weight at study initiation: 250-300 g
- Number of animals: 4
Administration / exposure
- Route of administration:
- other: intradermal
- Vehicle:
- not specified
- Details on exposure:
- ADMINISTRATION/EXPOSURE
- Preparation of test substance for induction: hapten alone and conjugation with guinea pig serum albumin (GPA)
- Induction schedule: multiple intradermal injections for 3-5 months, total dose ca. 250 µl
- Concentration in Freunds Complete Adjuvant (FCA): IPDI-GPA conjugate applied emulsified in FCA
- Challenge schedule: subcutaneous injection 5 days before being bled of animals - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no further details
- Duration of treatment / exposure:
- 3-5 months
- Frequency of treatment:
- Induction schedule: multiple intradermal injections for 3-5 months, total dose ca. 250 µl
- No. of animals per sex per dose:
- 4
- Details on study design:
- The immunologic evaluation of allergenic hapten-protein conjugates with isophorone diisocyanate (IPDI) was reported. The specificity of the
IPDI-ovalbumine was verified with antiserum by ELISA. The reactivity of guinea-pig sera to an IPDI-ovalbumine conjugate after aerosol- or
intradermal exposure of donor animals to IPDI was tested using ELISA optical density at 490 nm.
Examinations
- Observations and clinical examinations performed and frequency:
- not described
- Sacrifice and pathology:
- bleeding of animals 5 days after challenge, examinations not described
- Cell viabilities:
- not applicable
- Humoral immunity examinations:
- Examination of guinea pig sera for IgG1 and IgG2 with reactivity for hapten-conjugates
- Specific cell-mediated immunity:
- not described
- Non-specific cell-mediated immunity:
- not descibed
- Other functional activity assays:
- no
- Other examinations:
- attempts to demonstrate activity in these sera by passive hemagglutination have not been successful. However, absorption of positive sera with hapten-conjugate-bearing sheep red blood cells specifically reduced ELISA reactivity.
- Positive control:
- not described
- Statistics:
- not described
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Gross pathological findings:
- not specified
- Details on results:
- 7/8 intradermally injected guinea-pigs were positive for IgG1-antibody to IPDI. 4 had titer greater than 1/1000. None of 16
guinea-pigs exposed to IPDI aerosol showed a positive reaction (optical density > 0.22, dilution 1/20).
Specific immunotoxic examinations
- Cell viabilities:
- not specified
- Humoral immunity examinations:
- effects observed, treatment-related
- Specific cell-mediated immunity:
- not specified
- Non-specific cell-mediated immunity:
- not specified
- Other functional activity assays:
- not specified
- Other findings:
- effects observed, treatment-related
Effect levels
- Dose descriptor:
- other: IgG concentration measured as optical density at 490 nm
- Effect level:
- other: optical density at 490nm
- Sex:
- female
- Basis for effect level:
- other: no effect level described
Any other information on results incl. tables
no further remarks
Applicant's summary and conclusion
- Conclusions:
- Significant quantities of anaphylactically active class of immunoglobulin have been found in sera from guinea pigs sensitised to IPDI only by dermal exposure. No significant increase of anaphylactically active class of immunoglobulin have been found in sera from guinea pigs sensitised to IPDI by inhalation of IPDI aerosol.
- Executive summary:
The immunologic evaluation of allergenic Isophorone diisocyanate-protein conjugates was reported. Antibodies to the test item have been detected by an ELISA procedure. In detail, significant quantities of anaphylactically active class of immunoglobulin have been found in sera from guinea pigs sensitised to IPDI only by dermal exposure. No significant increase of anaphylactically active class of immunoglobulin have been found in sera from guinea pigs sensitised to IPDI by inhalation of IPDI aerosol. These antibodies were specifically inhibited by homologous hapten.
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