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Diss Factsheets
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EC number: 939-340-8 | CAS number: 28182-81-2
- 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
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Endpoint summary
Administrative data
Description of key information
Subchronic study: LOAEC: 21 mg/m³ (rat, 90 d, local)
Subacute study: LOAEC: 17.5 mg/m³ (rat, 15d, local)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- reliable
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 3.4 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- reliable
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity inhalation:
A subacute inhalation toxicity study was performed similar to the OECD testguideline 412 (Bayer, 1985). In brief, 10 male and 10 female Wistar rats each dose level were head-nose exposes to aerosols of Hexamethylene diisocyanate, oligomers (biuret). Exposure was for 6h daily on 5 consecutive days for 3 weeks (total of 15 exposures). The analytical determination of the exposure atmospheres resulted in respirable aerosol concentrations of 3.7, 17.5, 76.6 mg/m³. Mortality occurred in the high dose group (3/20 animals). Reversible and dose dependent clinical signs of respiratory irritation (e.g. repiratory distress), increase in lung weights and histopathological findings indicative for irritation of the upper and lower respiratory tract were observed in in the mid and high dose groups. With the lowest tested exposure atmosphere (3.7 mg/m³) no signs of respiratory irritation. Unspecific local irritation at the respiratory tract was identified as the key toxicological effect and in general no signs of systemic toxicity occurred.
A subchronic inhalation toxicity study was performed similar to the OECD testguideline 413 (Bayer, 1988). In brief, 10 male and 10 female Wistar rats each dose level were head-nose exposes to aerosols of Hexamethylene diisocyanate, oligomers (biuret). Exposure was for 6h daily on 5 consecutive days for 13 weeks. The analytical determination of the exposure atmospheres resulted in respirable aerosol concentrations of 0.4, 3.4 and 21 mg/m³. In addition to the assay parameters of the guideline lung function measurements (whole body plethysmography) were performed in 2 male and 2 female animals of each exposure group at the end of the exposure period.
In 7 of 20 animals of the high dose group (21 mg/m³) clinical symptoms (e.g. respiratory distress) were observed, 5 of these died or were sacrificed in a moribund state. Additionally slight and statistically significant increases in lung weights and histopathological findings indicative for pulmonary irritation were observed at this dose level (bronchioalveolar hyperplasia, mild focal histiocytosis). No histopathological findings at the upper respiratory tract were determined (trachea, olfactory epithelium, pharynx, larynx).
With the two lower tested aerosol concentrations (0.4, 3.4 mg/m³) no signs of respiratory irritation were observed. Unspecific local irritation at the respiratory tract was identified as the key toxicological effect and in general no signs of systemic toxicity occurred. In the performed lung function measurements no significant effects on breathing function were identified at all dose levels.
Both studies demonstrated that adverse effects were caused by unspecific irritation-related responses occurring predominantly in the lower respiratory tract. Indicators of pulmonary irritations were confined to mild respiratory distress, increased lung weights and histopathological findings in the bronchio-alveolar region (e.g. focal interstitial fibrosis, proliferation). The no observed adverse effect concentration was identified as 3.4 mg/m³ from the subchronic study (LOAEC 21 mg/m³) which well corresponded with results from the subacute study (NOAEC3.7 mg/m³, LOAEC 17.5 mg/m³), indicating that the observed effect pattern is not progressively increasing with exposure time.
Comparing all findings relevant for the determination of a NOAEC for Hexamethylene diisocyanate, oligomers (biuret), is suggesting a value in the range of 3-4 mg/m3 whether the exposure of rats was acute, subacute or subchronic (Pauluhn, 2001).
Justification for classification or non-classification
Dangerous substance Directive (67/548/EEC)
The available experimental test data are considered reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the criteria of Directive 67/548/EEC, as amended for the 28thtime in Directive 2001/59/EC, classification for STOT (RE) is not justified, due to lack of cumulative toxicity.
Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are considered reliable and suitable for the purpose of classification under Regulation 1272/2008. Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the 2ndtime in Directive EC 286/2011, classification for STOT (RE) is not justified, due to lack of cumulative toxicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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