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EC number: 212-485-8 | CAS number: 822-06-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Respiratory sensitisation
Administrative data
- Endpoint:
- respiratory sensitisation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- The technical exposure criteria specified in OECD Guideline No. 403 and the corresponding EC Guideline 892/69/EEC (1992) were fulfilled insofar as these are applicable to this study. General recommendations on the techniques used for the generation and characterization of atmospheres (ASTM E 981-84; Alarie, 1973) were observed. Specific, internationally harmonized test procedures for experiments to assess the lung sensitization potential of low- or high-molecular weight compounds are not currently available.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Hexamethylene diisocyanate
- EC Number:
- 212-485-8
- EC Name:
- Hexamethylene diisocyanate
- Cas Number:
- 822-06-0
- Molecular formula:
- C8H12N2O2
- IUPAC Name:
- 1,6-diisocyanatohexane
Constituent 1
Test animals
- Species:
- guinea pig
- Strain:
- other: Dunkin-Hartley Pirbright-White
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (Sulzfeld, Germany)
- Age at study initiation: approx. 2 weeks
- Housing: 4 per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Test system
- Route of induction exposure:
- other: intradermal and inhalation
- Route of challenge exposure:
- inhalation
- Vehicle:
- other: intradermal: desiccated corn oil - inhalation: vapour
- Concentration:
- see details on study design
- No. of animals per dose:
- 8
- Details on study design:
- Groups of eight female guinea-pigs were intradermally induced once per day on days 0, 2, and 4 (injection volume: 100 µl / 0.3 % solution in desiccated corn oil and one additional group of animals were exposed for five consecutive days (days 0 - 4) by inhalation (duration of exposure: 3 hrs/day) to average concentrations of 1,6 -hexamethylene diisocyanate (vapour) of 27.4 mg/m3 air. The latter group of animals received an additional single intradermal induction on day 0. Control animals received the vehicle alone (intradermally) under othenvise identical conditions (no inhalation exposure). During the recovery period (starting on day 21) a hapten-challenge (target concentrations: approximately 0.5 mg hapten/m3 air) was performed (challenge duration: 30 min). One day before and one day after the hapten-challenge an acetylcholine bronchoprovocation challenge (stepped concentrations in steps of 0.1%, 0.2%, 0.4% and 0.8%, w/v; duration of each 15-min) was performed. Following day 28 all guinea pigs were challenged again with the respective guinea pig serum albumin (GPSA) conjugate of the hapten (mean concentration: approximately 50 mg/m3 air). During and after challenge exposures immediate-onset respiratory reactions were evaluated by measurement of respiratory rate, tidal volume, respiratory minute volume, inspiratory and expiratory times, and peak expiratory flow rate. Additional parameters were derived mathematically. In some of the groups also measurements for delayed-onset responses were incorporated. On day after the GPSA-conjugate challenge, animals were sacrificed, and the lungs, including trachea and lung associated lymph nodes, were examined histopathologically. The weight of the excised lungs was determined. At sacrifice blood was sampled for serological examinations.
Results and discussion
- Results:
- Following induction, inflammatory skin reactions were observed. Also during the inhalation induction, signs indicative of respiratory tract irritation occurred. During or following hapten-challenges, the incidence of immediate-onset type respiratory reactions were roughly the same in all groups whereas during or following conjugate-challenges immediate-onset respiratory reactions occurred in a higher incidence in the 1,6-hexamethylene diisocyanate (HDI) sensitized groups when compared to the control groups. The comparison of both routes of induction demonstrates that the incidence of responding animals was not appreciably different when additional inhalation induction exposures were made. The acetylcholine bronchoprovocation challenge demonstrated that previous inhalation induction exposures to HDI do not evoke a conspicuous non-specific bronchial hyperreactivity. The histopathological investigations revealed inflammatory responses in those groups receiving inhalation induction exposures (bronchiolitis). Independent on the route of induction evidence of a specific airway eosinophilia and eosinophil infiltration into lung associated lymph nodes, a hallmark of allergic airway hyperresponsiveness, was observed. The serological investigations revealed a marked increase in anti-HDI IgG1-antibody titres.
Applicant's summary and conclusion
- Interpretation of results:
- sensitising
- Executive summary:
When animals that were sensitized intradermally or by inhalation and were subsequently challenged by inhalation with the respective hapten of 1,6 -hexamethylene diisocyanate no conclusive immediate-onset responses were observed. As a result of challenge with the respective conjugate of the hapten conclusive immediate-onset responses occurred. Additional evidence of a lung sensitizing potential was provided by the histopathological examination which revealed an increased eosinophilia of airways and lung associated lymph nodes as well as specific IgG1-antibody. Therefore, this study provides clear evidence that 1,6-hexamethylene diisocyanate is a respiratory sensitizer in the guinea pig bioassay.
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