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EC number: 242-060-2 | CAS number: 18172-67-3
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 14 weeks in 2005
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Recent study conducted by NTP similarly to OECD guideline 413 with deviations: food consumption, hematology, ophthalmological examination, some organ weights were not recorded.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- other: data available on NTP website
- Title:
- Unnamed
- Year:
- 2 006
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- food consumption, hematology, ophthalmological examination, some organ weights were not recorded
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Pin-2(3)-ene
- EC Number:
- 201-291-9
- EC Name:
- Pin-2(3)-ene
- Cas Number:
- 80-56-8
- Molecular formula:
- C10H16
- IUPAC Name:
- 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
- Details on test material:
- Purity ≥ 97%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- After a 10- to 14-day quarantine period, animals are assigned at random to treatment groups.
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Remarks on MMAD:
- MMAD / GSD: no data
- Details on inhalation exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 14 weeks; 6 hours per day
- Frequency of treatment:
- five times per week, weekdays only
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
25 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
50 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
100 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
200 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
400 ppm
Basis:
nominal conc.
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- No
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes for moribundity and death
Time schedule: twice daily, at least 6 hours apart (before 10:00 AM and after 2:00 PM)
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
Time schedule for examinations: on Day 1 of the test, after 7 days and at weekly intervals thereafter
FOOD CONSUMPTION: No
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: Yes
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- no data
- Statistics:
- Kaplan-Meier used for probability of survival. Statistical analyses used for possible dose-related effect on survival was Cox (Cox D.R. (1972) Regression models and life tables. J.R. Stat. Soc. B34: 187-220.) for testing two groups for equality; and Tarone’s (Tarone R.E. (1975) Tests for trend in life table analysis. Biometrika 62; 679-682) life table test for a dose-related trend.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- MORTALITY
In the high dose group (400 ppm), 6 females were found dead before the end of the study (4 on Day 36, 1 on Day 50 and 1 on Day 91). All other animals survived until terminal sacrifice.
CLINICAL EXAMINATION
Three females of the high dose group (which survived until terminal sacrifice) displayed mild tremors.
BODY WEIGHT AND WEIGHT GAIN
Males: during the first week of treatment, the body weight gain was slightly lower in all treated groups when compared to the control group. The overall bodyweight gain was significantly lower in the high dose group (197 g vs 224 g in the control group).
Females: during the first week of treatment, the body weight gain was lower in the high dose group only when compared to the treated group. Thereafter the mean bwg of females in the high dose group was variable but overall approximately half this of the control group. All surviving females at 400 ppm lost weight between week 12 and week 14.
CLINICAL CHEMISTRY
Males showed statistically significant reductions in sorbitol dehydrogenase activity at 400 ppm, alanine aminotransferase activity at levels ≥50 ppm, and alkaline phosphatase activity at levels ≥100 ppm. Females showed statistically significant reductions in alanine aminotransferase activity at levels ≥200 ppm, and alkaline phosphatase activity at the 400 ppm. There were significant decreases at lower levels of exposure for females but these changes were not dose-dependent. None of these changes in enzyme activity were related to organ weight changes or evidence of histopathology.
ORGAN WEIGHTS
Absolute and relative liver weights were statistically increased in males at 200 ppm and greater and relative and absolute kidney weights were increased in males at 100 ppm and greater. In females, relative and absolute liver weights were increased at levels of ≥50 ppm, but there were no increases in either hepatic enzymes or any evidence of histopathological changes at any of these dose levels.
Females showed statistically significant decreases in absolute and relative thymus weights and increased relative lung weight at the 400 ppm level.
HISTOPATHOLOGY: NON-NEOPLASTIC
Examination of the male kidneys at all dose levels revealed lesions including granular casts and hyaline droplets indicative of α2u-globulin nephropathy.
In females there was no evidence of histopathology in any organ at any dose level. Specifically, there was no evidence of histopathological changes to the clitoris, ovaries, uterus, epididymis, preputial gland, seminal vesicles, and testes for any of the control or test groups of animals.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 25 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Nephropathy which is relevant only in male rats. Lower body weight gain in the high dose group. In humans, this LOAEL will not be relevant.
- Dose descriptor:
- NOAEL
- Effect level:
- 200 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Based on mortality and lower body weight gain in the high dose group.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1 - Mean body weight gain (g) in males
Dose Group | Wk 1-2 | Wk 1-14 |
Vehicle Control | 55.6 | 224 |
25 ppm | 45.7 | 212 |
50 ppm | 49.2 | 221 |
100 ppm | 36.6 | 207 |
200 ppm | 46.0 | 216 |
400 ppm | 33.2 | 197 |
Table 2 - Mean body weight gain (g) in females
Dose Group | Wk 1-2 | Wk 1-14 |
Vehicle Control | 26.4 | 99 |
25 ppm | 25.1 | 101 |
50 ppm | 27.5 | 109 |
100 ppm | 19.0 | 99 |
200 ppm | 22.7 | 105 |
400 ppm | 16.2 | 57 |
Applicant's summary and conclusion
- Conclusions:
- The LOAEL in male rats is the lowest dose level tested, but it is not relevant to humans as it is based on renal effects linked to alpha2µ-globulin accumulation. When considering effects other than those on kidneys in males, a lower body weight gain was observed at 400 ppm when compared to controls.
A NOAEL could be defined in female rats at 200 ppm on the basis of mortality and a lower body weight gain at the next dose level when compared to controls.
The overall NOAEL relevant for humans is 200 ppm, equivalent to ca. 170 mg/kg bw/day. - Executive summary:
In a 90-day inhalation study conducted by NTP similarly to OECD guideline 413, groups of 10 animals per dose and per sex were administered for 6 hours per day, 5 weekdays per week at 0, 25, 50, 100, 200 and 400 ppm for a total of 14 weeks. The animals were observed twice per day and weighed once per week. A complete histopathologic evaluation including treatment-related gross lesions was performed on all animals, including early death animals. Treatment-related lesions (target organs) were identified and these organs and gross lesions were examined to a no-effect level.
Apart from lesions including granular casts and hyaline droplets indicative of alpha2µ-globulin nephropathy observed in all treated group males, a lower body weight gain than in controls was observed in the high dose group in both sexes. In addition, 6 females died and 3 females displayed mild tremors in the high dose group too.
The LOAEL in male rats is the lowest dose level tested, but it is not relevant to humans as it is based on renal effects linked to alpha2µ-globulin accumulation. When considering effects other than those on kidneys in males, a lower body weight gain was observed at 400 ppm when compared to controls. A NOAEL could be defined in female rats at 200 ppm on the basis of mortality and a lower body weight gain at the next dose level when compared to controls. Mortality was observed in female rats in the high dose group. As no specific target organ was sufficiently impaired by the treatment to cause mortality, it may be concluded that these deaths have a general systemic toxicity origin.
The overall NOAEL relevant for humans is 200 ppm.
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.
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