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EC number: 202-046-9 | CAS number: 91-17-8
- 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
Endpoint summary
Administrative data
Description of key information
Subacute studies on oral repeated dose toxicity in rats are available. Subcaute and subchronic repeated dose toxicity studies in rats, mice, dogs and guinea pigs with inhalation exposure to decahydronaphthalene are available (see below "Additional information"). No data available on repeated dermal exposure with the test item. A data waiver is claimed.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
- Principles of method if other than guideline:
- daily oral dosing up to 28 days
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- no data
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- no data
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
- Remarks:
- Doses / Concentrations:
0, 10, 100, 1000 mg/kg bw/d
Basis:
actual ingested - No. of animals per sex per dose:
- 30 male
5 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- 5 males each were sacrificed on days 1, 3, 7, 14, 28 and 14 days post -treatment
5 females were sacrificed on day 28 - Positive control:
- no data
- Observations and examinations performed and frequency:
- no data
- Sacrifice and pathology:
- no data
- 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
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- kidney toxicity in male rats at dose levels >10 mg/kg bw/d
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Increased incidences of hyaline droplets in the renal proximal tubule cells of male rats, increased cell turnover, and focal renal tubule damage were seen in the 100 and 1,000 mg/kg groups.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no adverse effects were seen up to the highest dose level
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 10 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Kidney toxicity, hyaline droplets
- Critical effects observed:
- not specified
- Conclusions:
- Male specific kidney toxicity was observed upon oral administration of decahydronaphthalene at dose levels of 100 and 1000 mg/kg bw/d administered by gavage. Hystology of kidneys identified possible mechanism for this sex and species specific toxicity.
- Executive summary:
Kidneys from male and female Wistar rats dosed with Decalin, were examined by light and electron microscopy. Paraffin histology showed hyaline droplet accumulation in the renal proximal tubular cells of the male rats. Resin histology at both the light and electron microscope level, along with cytochemical procedures for acid phosphatase and the protein 'alpha 2U globulin', helped further in the characterisation of these cytoplasmic inclusions. These techniques confirmed that the accumulation of hyaline droplets seen by paraffin histology represented an increase in the size and number of secondary lysosomes which have been shown to be involved in protein uptake and metabolism. Time course studies showed that increased numbers of small dense lysosomes appear first, which then increase in size, presumably by fusion. Crystalloid bodies form in these large lysosomes eventually giving rise to rectilinear bodies. The accumulation of these protein laden secondary lysosomes took place primarily in the cells of the S1 and S2 segments of the proximal tubules. In extreme cases of lysosomal accumulation however, loading of the S3 segments was noted. In tubules where cellular inclusion loading was heavy, there was evidence of increased cell turnover. The kidneys of female rats appeared normal.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Klimisch 2 (reliable with restrictions)
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1996-09-16 to 1996-12-18
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to Guideline study
- Principles of method if other than guideline:
- Repeated Dose Toxicity, U.S. NTP
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS
- Source: Taconic Laboratory Animals and Services, Germantown (NY, USA)
- Age: 6 weeks at study initiation
- Weight at study initiation: males mean 97 g, females mean 90 g (core study)
Number of animals: total 25 males + 20 females per exposure concentration
- Food a(d libitum except during exposure and urine collection periods), irradiated: NTP-2000 open formula pelleted diet (Zeigler Brothers, Inc., Gardners, PA)
- Water (ad libitum): tap water
- Housing: individually in Stainless-steel wire bottom (Hazleton System, Inc., Aberdeen, MD)
ENVIRONMENTAL CONDITIONS (CHAMBER)
- Temperature: 72° ± 3° F
- Relative humidity: 50% ± 15%
- Room fluorescent light: 12 hours/day
- Chamber air changes: 15/hour - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: clean air
- Details on inhalation exposure:
- ADMINISTRATION / EXPOSURE
- Duration of exposure:
2 weeks: 5 male renal toxicity rats
6 weeks: 10 male + 10 female clinical pathology rats
14 weeks: 10 male + 10 female core study rats
- Type of exposure: whole-body inhalation
- Vehicle: clean air
- Concentration in vehicle: established within 12 minutes, monitored every 24 minutes At 72 +- 3 °F (22.2 °C) the ppm concentrations
correspond to: 143, 285, 570, 1141, 2282 mg/m3 - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations in the exposure chambers were monitored every 24 minutes by an on-line gas chromatograph
- Duration of treatment / exposure:
- 2, 6, or 14 weeks; 1 additional day before end of study
- Frequency of treatment:
- 6 hours (+ 12 minutes concentration buildup)/day, 5 days/week
- Remarks:
- Doses / Concentrations:
25, 50, 100, 200, 400 ppm
Basis: analytical conc. - No. of animals per sex per dose:
- 25 male and 20 female rats
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: observed twice daily
- Mortality: observed twice daily
- Clinical findings: weekly
- Body weight: initially, weekly, end of study
- Hematology: Blood sampling on days 3 and 23 (clinical pathology group) or at end of study (core
study group). Determination of hematocrit; packed red cell volume; hemoglobin; erthrocyte, reticulocyte, nucleated erythrocyte, and platelet counts; mean cell volume; mean cell hemoglobin; mean cell hemoglobin concentration; and leukocyte count and differentials
- Biochemistry: Urea nitrogen, creatinine, total protein, albumin, globulin, albumin/globulin ratio, alanine aminotransferase, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and bile acids
- Urinalysis: sampling during week 12. Determination of creatinine, glucose, glucose/creatinine ratio, protein, protein/creatinine ratio, alkaline phosphatase, alkaline phosphatase/creatinine ratio, alkaline aminotransferase, aspartate aminotransferase, aspartate aminotransferase/creatinine ratio, lactate dehydrogenase, lactate dehydrogenase/creatinine ratio, gamma-glutamyltransferase, gamma-glutamyltransferase/creatinine ratio, N-acetyl-beta-D-glucosaminidase, N-acetyl-beta-D-glucosaminidase/creatinine ratio, volume, and specific gravity
OTHER EXAMINATIONS:
- Sperm motility: Collection of sperm samples from 0, 100, 200, and 400 ppm males at the end of the study. Evaluation of: spermatid heads per
testis, per gram testis, per cauda, and per gram cauda and epididymal spermatozoal motility. The left cauda, left epididymis, and left testis were
weighed.
- Vaginal cytology: Collection of vaginal samples for up to 12 consecutive days prior to the end of the study from 0, 100, 200, or 400 ppm females.
The percentage of time spent in the various estrous cycle stages and estrous cycle length were evaluated.
- Renal effects: 16 hour-urine samples (all exposure concentrations) from
- 2 weeks: 5 male renal toxicity + 5 female clinical pathology rats: volume and decalol excretion;
- 6 weeks: 5 male + 5 female clinical pathology rats: volume and decalol excretion;
- 12 weeks:10 male + 10 female core study rats: volume.
Urine analysis (all exposure groups) for
- weeks 2 and 6: decalol and creatinine
- week 12: creatinine Right kidney sample analysis (all male groups) for
- weeks 2, 6, and 14: cis- and trans-decahydronaphthalene, cis- and trans-decahydro-2-naphthalone, a2u-globulin Right kidney sample analysis
(females) for
- week 14: cis- and trans-decahydronaphthalene Calculation of several concentration ratios.
- Assessment of cell proliferation: Analysis of left kidney sections and duodenum from
- 5 male renal toxicity rats (2 weeks),
- 5 male clinical pathology rats (6 weeks),
- 5 or 10 male core study rats (14 weeks) - Sacrifice and pathology:
- SACRIFICE
Carbon dioxide asphyxiation
PATHOLOGY
Necropsy was performed on all core study animals. Organs weighed were the heart, right kidney, liver, lung, right testis, and thymus.
- Weights: heart, right kidney, liver, lung, right testis, thymus
- Macroscopic: yes, no details reported
- Microscopic: 0 and 400 ppm core study rats: gross lesions, adrenal gland, bone with marrow, brain, clitoral gland, esophagus, heart, large intestine (cecum, colon, rectum), small intestine (duodenum, jejunum, ileum), kidney, larynx, liver, lung, lymph nodes (mandibular, mesenteric, bronchial, and mediastinal), mamary gland, nose, ovary, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skin, spleen, stomach (forestomach and glandular), testis with epididymis and semial vesicle, thymus, thyroid gland, trachea, urinary bladder, and uterus
Other groups: kidney of male rats. - Statistics:
- STATISTICAL METHODS: not specifically reported; general data compiled with carcinogenicity study data in chapter 5.7
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no clinical findings related to exposure.
- Mortality:
- no mortality observed
- Description (incidence):
- All rats survived to the end of the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Mean body weights of exposed groups were similar to those of the control groups.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- Several transient observations were minimal and not considered toxicologically relevant
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Several transient observations were minimal and not considered toxicologically relevant
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant findings were consistent with the renal toxicity data and the renal lesions observed microscopically:
increase in glucose/creatinine ratio (males >= 25 ppm: 20-93 %)
increase in protein/creatinine ratio (males >= 25 ppm: 19-44 %)
increase in aspartate aminotransferase/creatinine ratio (males >= 25 ppm: 4.9-6.7fold, females >= 50 ppm: 1.7-2.3fold)
increase in lactate dehydrogenase/creatinine ratio (males and females >= 25 ppm: 3.0-4.2fold and 1.5-2.1fold, respetively) - Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute and/or relative kidney and liver weights of male rats exposed to >= 50 ppm were increased, s. "Any other information on results incl. tables"
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Incidences and/or severities of hyaline droplet accumulation and renal tubule regeneration in the kidney generally increased with increasing exposure concentration. Granular casts were seen in the kidney at 6 weeks and at terminal sacrifice.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- Concentrations of a2u-globulin in the kidney as well as the a2u globulin/soluble protein ratios were significantly increased in the 200 and 400 ppm males at weeks 2, 6, and 14. Sperm motility and vaginal cytology parameters were not affected by exposure.
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 25 ppm
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- urinalysis
- Dose descriptor:
- LOAEC
- Effect level:
- > 25 ppm
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Critical effects observed:
- not specified
- Conclusions:
- Urinalysis showed significant findings (increase in lactate dehydrogenase/creatinine ratio and in aspartate aminotransferase/creatinine ratio) in male and female rats exposed to 25 ppm and greater. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm were increased. Females were not affected. So the changes in enzyme urine levels in female rats are not adverse effects, because they are not related to any simultaneous increase of kidney weight damage and therefore, 25 ppm is determined to be the no observed effect concentration (NOAEC) in female rats in this 90 day study.
Furthermore, Decahydronaphthalene causes male rat-specific alpha2u-globulin nephropathy. This type of kidney toxicity characterised by increased formation of hyaline droplets, increased concentration of alpha2u-globulin results in increased cell proliferation and may increase renal adenoma and carcinoma rates. Because the mechanism has been established as species and sex-specific for the male rat it is generally considered to be of no relevance for human health, endpoints resulting from male nephrotoxicity are not considered as relevant. - Executive summary:
Groups of 25 male and 20 female F344/N rats were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 2 (five male renal toxicity rats), 6 (10 male and 10 female clinical pathology rats), or 14 (10 core study rats) weeks. All rats survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber control groups. Urinalysis results indicated that decalin exposure caused increases in urine glucose and protein concentrations and enzyme activities that were consistent with the renal lesions observed microscopically. Renal toxicity studies were performed on rats sacrificed at 2 and 6 weeks and at the end of the study. In kidney tissue examined for cell proliferation, the numbers of PCNA-labeled cells and labeling indices were generally significantly greater than those of the chamber controls in exposed groups of rats at all three time points. Concentrations of alpha2u-globulin in the kidney as well as the alpha2u-globulin/soluble protein ratios were significantly increased at week 2 in all exposed groups and in the 200 and 400 ppm groups at week 6 and at the end of the study. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm or greater were increased. Females were not affected. Incidences of renal tubule regeneration and granular casts in the medulla of the kidney in exposed male rats were increased, and the severities of hyaline droplets generally increased with increasing exposure concentration.
Reference
Concentration | Kidney | Liver | ||
absolute | relative | absolute | relative | |
25 ppm | +5.8 % | +4.5 % * | +5.5 % | +3.9 % |
50 ppm | +5.3 % | +7.9 % ** | +5.1 % | +8.0 % ** |
100 ppm | +3.3 % | +7.7 % ** | +1.2 % | +5.5 % ** |
200 ppm | +15.0 % ** | +11.5 % ** | +12.1 % ** | +8.7 % ** |
400 ppm | +19.8 % ** | +19.6 % ** | +11.2 % ** | +10.9 % ** |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 143 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Klimisch 1 (reliable without restrictions)
- System:
- urinary
- Organ:
- kidney
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1996-09-16 to 1996-12-18
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to Guideline study
- Principles of method if other than guideline:
- Repeated Dose Toxicity, U.S. NTP
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS
- Source: Taconic Laboratory Animals and Services, Germantown (NY, USA)
- Age: 6 weeks at study initiation
- Weight at study initiation: males mean 97 g, females mean 90 g (core study)
Number of animals: total 25 males + 20 females per exposure concentration
- Food a(d libitum except during exposure and urine collection periods), irradiated: NTP-2000 open formula pelleted diet (Zeigler Brothers, Inc., Gardners, PA)
- Water (ad libitum): tap water
- Housing: individually in Stainless-steel wire bottom (Hazleton System, Inc., Aberdeen, MD)
ENVIRONMENTAL CONDITIONS (CHAMBER)
- Temperature: 72° ± 3° F
- Relative humidity: 50% ± 15%
- Room fluorescent light: 12 hours/day
- Chamber air changes: 15/hour - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: clean air
- Details on inhalation exposure:
- ADMINISTRATION / EXPOSURE
- Duration of exposure:
2 weeks: 5 male renal toxicity rats
6 weeks: 10 male + 10 female clinical pathology rats
14 weeks: 10 male + 10 female core study rats
- Type of exposure: whole-body inhalation
- Vehicle: clean air
- Concentration in vehicle: established within 12 minutes, monitored every 24 minutes At 72 +- 3 °F (22.2 °C) the ppm concentrations
correspond to: 143, 285, 570, 1141, 2282 mg/m3 - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations in the exposure chambers were monitored every 24 minutes by an on-line gas chromatograph
- Duration of treatment / exposure:
- 2, 6, or 14 weeks; 1 additional day before end of study
- Frequency of treatment:
- 6 hours (+ 12 minutes concentration buildup)/day, 5 days/week
- Remarks:
- Doses / Concentrations:
25, 50, 100, 200, 400 ppm
Basis: analytical conc. - No. of animals per sex per dose:
- 25 male and 20 female rats
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: observed twice daily
- Mortality: observed twice daily
- Clinical findings: weekly
- Body weight: initially, weekly, end of study
- Hematology: Blood sampling on days 3 and 23 (clinical pathology group) or at end of study (core
study group). Determination of hematocrit; packed red cell volume; hemoglobin; erthrocyte, reticulocyte, nucleated erythrocyte, and platelet counts; mean cell volume; mean cell hemoglobin; mean cell hemoglobin concentration; and leukocyte count and differentials
- Biochemistry: Urea nitrogen, creatinine, total protein, albumin, globulin, albumin/globulin ratio, alanine aminotransferase, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and bile acids
- Urinalysis: sampling during week 12. Determination of creatinine, glucose, glucose/creatinine ratio, protein, protein/creatinine ratio, alkaline phosphatase, alkaline phosphatase/creatinine ratio, alkaline aminotransferase, aspartate aminotransferase, aspartate aminotransferase/creatinine ratio, lactate dehydrogenase, lactate dehydrogenase/creatinine ratio, gamma-glutamyltransferase, gamma-glutamyltransferase/creatinine ratio, N-acetyl-beta-D-glucosaminidase, N-acetyl-beta-D-glucosaminidase/creatinine ratio, volume, and specific gravity
OTHER EXAMINATIONS:
- Sperm motility: Collection of sperm samples from 0, 100, 200, and 400 ppm males at the end of the study. Evaluation of: spermatid heads per
testis, per gram testis, per cauda, and per gram cauda and epididymal spermatozoal motility. The left cauda, left epididymis, and left testis were
weighed.
- Vaginal cytology: Collection of vaginal samples for up to 12 consecutive days prior to the end of the study from 0, 100, 200, or 400 ppm females.
The percentage of time spent in the various estrous cycle stages and estrous cycle length were evaluated.
- Renal effects: 16 hour-urine samples (all exposure concentrations) from
- 2 weeks: 5 male renal toxicity + 5 female clinical pathology rats: volume and decalol excretion;
- 6 weeks: 5 male + 5 female clinical pathology rats: volume and decalol excretion;
- 12 weeks:10 male + 10 female core study rats: volume.
Urine analysis (all exposure groups) for
- weeks 2 and 6: decalol and creatinine
- week 12: creatinine Right kidney sample analysis (all male groups) for
- weeks 2, 6, and 14: cis- and trans-decahydronaphthalene, cis- and trans-decahydro-2-naphthalone, a2u-globulin Right kidney sample analysis
(females) for
- week 14: cis- and trans-decahydronaphthalene Calculation of several concentration ratios.
- Assessment of cell proliferation: Analysis of left kidney sections and duodenum from
- 5 male renal toxicity rats (2 weeks),
- 5 male clinical pathology rats (6 weeks),
- 5 or 10 male core study rats (14 weeks) - Sacrifice and pathology:
- SACRIFICE
Carbon dioxide asphyxiation
PATHOLOGY
Necropsy was performed on all core study animals. Organs weighed were the heart, right kidney, liver, lung, right testis, and thymus.
- Weights: heart, right kidney, liver, lung, right testis, thymus
- Macroscopic: yes, no details reported
- Microscopic: 0 and 400 ppm core study rats: gross lesions, adrenal gland, bone with marrow, brain, clitoral gland, esophagus, heart, large intestine (cecum, colon, rectum), small intestine (duodenum, jejunum, ileum), kidney, larynx, liver, lung, lymph nodes (mandibular, mesenteric, bronchial, and mediastinal), mamary gland, nose, ovary, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skin, spleen, stomach (forestomach and glandular), testis with epididymis and semial vesicle, thymus, thyroid gland, trachea, urinary bladder, and uterus
Other groups: kidney of male rats. - Statistics:
- STATISTICAL METHODS: not specifically reported; general data compiled with carcinogenicity study data in chapter 5.7
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no clinical findings related to exposure.
- Mortality:
- no mortality observed
- Description (incidence):
- All rats survived to the end of the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Mean body weights of exposed groups were similar to those of the control groups.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- Several transient observations were minimal and not considered toxicologically relevant
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Several transient observations were minimal and not considered toxicologically relevant
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant findings were consistent with the renal toxicity data and the renal lesions observed microscopically:
increase in glucose/creatinine ratio (males >= 25 ppm: 20-93 %)
increase in protein/creatinine ratio (males >= 25 ppm: 19-44 %)
increase in aspartate aminotransferase/creatinine ratio (males >= 25 ppm: 4.9-6.7fold, females >= 50 ppm: 1.7-2.3fold)
increase in lactate dehydrogenase/creatinine ratio (males and females >= 25 ppm: 3.0-4.2fold and 1.5-2.1fold, respetively) - Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute and/or relative kidney and liver weights of male rats exposed to >= 50 ppm were increased, s. "Any other information on results incl. tables"
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Incidences and/or severities of hyaline droplet accumulation and renal tubule regeneration in the kidney generally increased with increasing exposure concentration. Granular casts were seen in the kidney at 6 weeks and at terminal sacrifice.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- Concentrations of a2u-globulin in the kidney as well as the a2u globulin/soluble protein ratios were significantly increased in the 200 and 400 ppm males at weeks 2, 6, and 14. Sperm motility and vaginal cytology parameters were not affected by exposure.
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 25 ppm
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- urinalysis
- Dose descriptor:
- LOAEC
- Effect level:
- > 25 ppm
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Critical effects observed:
- not specified
- Conclusions:
- Urinalysis showed significant findings (increase in lactate dehydrogenase/creatinine ratio and in aspartate aminotransferase/creatinine ratio) in male and female rats exposed to 25 ppm and greater. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm were increased. Females were not affected. So the changes in enzyme urine levels in female rats are not adverse effects, because they are not related to any simultaneous increase of kidney weight damage and therefore, 25 ppm is determined to be the no observed effect concentration (NOAEC) in female rats in this 90 day study.
Furthermore, Decahydronaphthalene causes male rat-specific alpha2u-globulin nephropathy. This type of kidney toxicity characterised by increased formation of hyaline droplets, increased concentration of alpha2u-globulin results in increased cell proliferation and may increase renal adenoma and carcinoma rates. Because the mechanism has been established as species and sex-specific for the male rat it is generally considered to be of no relevance for human health, endpoints resulting from male nephrotoxicity are not considered as relevant. - Executive summary:
Groups of 25 male and 20 female F344/N rats were exposed to 0, 25, 50, 100, 200, or 400 ppm decalin vapor 6 hours per day, 5 days per week for 2 (five male renal toxicity rats), 6 (10 male and 10 female clinical pathology rats), or 14 (10 core study rats) weeks. All rats survived to the end of the study, and mean body weights of exposed groups were similar to those of the chamber control groups. Urinalysis results indicated that decalin exposure caused increases in urine glucose and protein concentrations and enzyme activities that were consistent with the renal lesions observed microscopically. Renal toxicity studies were performed on rats sacrificed at 2 and 6 weeks and at the end of the study. In kidney tissue examined for cell proliferation, the numbers of PCNA-labeled cells and labeling indices were generally significantly greater than those of the chamber controls in exposed groups of rats at all three time points. Concentrations of alpha2u-globulin in the kidney as well as the alpha2u-globulin/soluble protein ratios were significantly increased at week 2 in all exposed groups and in the 200 and 400 ppm groups at week 6 and at the end of the study. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm or greater were increased. Females were not affected. Incidences of renal tubule regeneration and granular casts in the medulla of the kidney in exposed male rats were increased, and the severities of hyaline droplets generally increased with increasing exposure concentration.
Reference
Concentration | Kidney | Liver | ||
absolute | relative | absolute | relative | |
25 ppm | +5.8 % | +4.5 % * | +5.5 % | +3.9 % |
50 ppm | +5.3 % | +7.9 % ** | +5.1 % | +8.0 % ** |
100 ppm | +3.3 % | +7.7 % ** | +1.2 % | +5.5 % ** |
200 ppm | +15.0 % ** | +11.5 % ** | +12.1 % ** | +8.7 % ** |
400 ppm | +19.8 % ** | +19.6 % ** | +11.2 % ** | +10.9 % ** |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- Klimisch 1 (reliable without restrictions)
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: dermal
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- chronic toxicity: dermal
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
No adverse effects were observed upon repeated oral exposure at dose levels up to 1000 mg/kg bw/day.
In the 90-day inhalation study (NTP 2005) urinalysis showed significant findings (increase in lactate dehydrogenase/creatinine ratio and in aspartate aminotransferase/creatinine ratio) in male and female rats exposed to 25 ppm and greater. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm were increased. Females were not affected. So, the changes in enzyme urine levels in female rats are not adverse effects, because they are not related to any simultaneous increase of kidney weight damage and therefore, 25 ppm (143 mg/m3) is determined to be the no observed effect concentration (NOAEC) in female rats in this 90-day study.
Decahydronaphthalene causes male rat-specific alpha2u-globulin nephropathy. This type of kidney toxicity characterised by increased formation of hyaline droplets, increased concentration of alpha2u-globulin results in increased cell proliferation and may increase renal adenoma and carcinoma rates. Because the mechanism has been established as species and sex-specific for the male rat it is generally considered to be of no relevance for human health, endpoints resulting from male nephrotoxicity are not considered as relevant.
Furthermore, increase liver weight even at the lowest dose level (LOAEC) of 25 ppm (143 mg/m³) in rats was observed in a 16-day inhalation study with rats. As this effect was not observed in the 90-day inhalation study (NTP 2005) it indicates that this effect is rather reversible and hence the LOAEC was not used as starting point for the derivation of the DNEL (see chapter 5.11. of CSR).
Summary of repeated dose toxicity studies with decahydronaphthalene
Route | Type of study | NOAEL/NOAEC | LOAEL/LOAEC | Effect | Reference |
oral | Rat 30 days | 1000 mg/kg bw/d | - | - | Read 1988 |
Rat, male 30 days | 10 mg/kg bw/d | 100 mg/kg bw/d | Males:Kidney, hyaline droplets | Read 1988 | |
inhalation | Rat 14-days | - | 25 ppm 143 mg/m³ | Liver weight | NTP 2005 |
Rat 90-days | 25 ppm 143 mg/m³ | > 25 ppm > 143 mg/m³ | Increase in lactate dehydrogenase/creatinine ratio in males and females | NTP 2005 | |
Mouse 14-days | 50 ppm 285 mg/m³ | 100 ppm 570 mg/m³ | Liver weight | NTP 2005 | |
Mouse 90-days | 25 ppm 143 mg/m³ | 50 ppm 285 mg/m³ | Liver cytomegaly | NTP 2005 | |
Rat, male, 30 days |
| 50 ppm 285 mg/m³ | Reduced body weight | MacEwen 1978 | |
Mouse, female 30 days | 50 ppm 285 mg/m³ | 250 ppm 1425 mg/m³ | Liver, vacuolisation | MacEwen 1978 | |
Guineapig, male, 30 days | - | 50 ppm 285 mg/m³ | Reduced body weight | MacEwen 1978 | |
Rat, female, 90 days | - | 50 ppm 285 mg/m³ | - | MacEwen 1979 | |
Rat, male, 90 days | 5 ppm | - | Males:Kidney, hyaline droplets | MacEwen 1979 | |
Mouse, female 90 days | - | 50 ppm 285 mg/m³ | - | MacEwen 1979 | |
dog, male+female 90 days | - | 50 ppm 285 mg/m³ | - | MacEwen 1979 | |
Rat 20 days | - | 200 ppm 1148 mg/m³ | - | Gage 1970 | |
Rat female 28 days | - | 125 ppm 710 mg/m³ | increased relative liver weight | Stone 1987 | |
Rat female 35 days | - | 25 ppm 143 mg/m³ | Males:Kidney, hyaline droplets | Stone 1987 |
Repeated dose toxicity: inhalation - systemic effects (target organ) digestive: liver; urogenital: kidneys
Justification for classification or non-classification
According to the criteria of CLP Regulation 1272/2008 the test item is not classified because it has a low oral repeated dose toxicity.
Effects observed in a repeated inhalation toxicity study (findings in liver and kidney) do not meet the criteria for classification and labelling.
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