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EC number: 265-200-4 | CAS number: 64742-96-7 A complex combination of hydrocarbons obtained from the distillation of crude oil or natural gasoline. It consists predominantly of saturated hydrocarbons having carbon numbers predominantly in the range of C11 through C16 and boiling in the range of approximately 190°C to 290°C (374°F to 554°F).
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study is classified as reliable without restrictions because it was carried out in a method similar/equivalent to OECD TG 413.
Data source
Reference
- Reference Type:
- publication
- Title:
- A 90-day continuous vapor inhalation toxicity study of JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 rats and C57BL/6 mice
- Author:
- Mattie, D.R., Alden, C.L., Newell, T.K., Gaworski, C.L., Flemming, C.D.
- Year:
- 1 991
- Bibliographic source:
- Toxicologic Pathology 19(2):77-87
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- Only 2 concentrations were used
- GLP compliance:
- not specified
Test material
- Reference substance name:
- most likely 8008-20-6
- IUPAC Name:
- most likely 8008-20-6
- Reference substance name:
- JP-8 jet fuel
- IUPAC Name:
- JP-8 jet fuel
- Test material form:
- other: low viscosity liquid hydrocarbon
- Details on test material:
- - Name of test material (as cited in study report): JP-8 jet fuel
- Substance type:Kerosine
- Physical state: Liquid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Rats: Charles River Breeding Laboratory, Wilmington, Massachusetts
- Age at study initiation: Approximately 10 weeks old
- Housing: gang-caged
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:Thomas Dome inhalation chambers (25 cubic meters) with heated glass evaporation towers through which the test material was passed, an air stream flowing through the tower carried the vapours into the main chamber
- Method of holding animals in test chamber: Each chamber housed numerous animals in stainless steel, wire-mesh cages.
TEST ATMOSPHERE
- Brief description of analytical method used: A gas chromatograph trace of the sample of each drum as it entered the exposure chamber to ensure consistency over the study period. A gas chromatograph trace was routinely obtained for each chamber every 2 weeks.
- Samples taken from breathing zone: yes/no
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Constant (24 hours a day) for the 90 days
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500, or 1000 mg/m3
Basis:
other: nominal conc. (vapour)
- No. of animals per sex per dose:
- 95 male rats per dose; 75 female rats per dose
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: Not reported
- Rationale for selecting satellite groups: Not reported
- Post-exposure recovery period in satellite groups: Male rats: 2 weeks, 2 months, 9 months, and 21 months; female rats: 9 and 21 months
- Section schedule rationale (if not random): Not reported
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes on rats; no on mice
- Time schedule for examinations: Biweekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of exposure period, 2 weeks and 2 and 21 months after exposure termination
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: All rats sacrificed at the end of exposure; 10 male rats per group at 2 weeks and 2 months; 10 male rats and 10 female rats at final sacrifice (21 months)
- Parameters measured were not specified.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:At the end of the exposure period, 2 weeks and 2 and 21 months after exposure termination
- Animals fasted: No data
- How many animals: All rats sacrificed at the end of the exposure period; 10 male rats per group at 2 weeks and 2 months; 10 male rats and 10 female rats at final sacrifice (21 months)
- Parameters measured were not specified.
URINALYSIS: Yes
- Time schedule for collection of urine: Pre-exposure and at each scheduled sacrifice
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters measured were only specified as including cell count and osmolarity.
NEUROBEHAVIOURAL EXAMINATION: No
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, a detailed list of tissues was not provided and it is stated that approximately 40 tissues per animal were fixed for routine histopathology. - Other examinations:
- Rat liver, kidney, and spleen were weighed.
- Statistics:
- A repeated measures analysis of variance was used to analyze body weights. Possible differences between the sexes were examined using a 2-way analysis of variance. Haematology, clinical chemistry, and organ weights were analyzed using a 2 or 3 factorial analysis of variance. Bonferoni correction was used where appropriate. Tumour data were analysed using a chi-square test for proportions and an Armitage Test for Trends. Bonferoni corrections of the Fisher Exact Test or Bates Exact Chi-square were used where appropriate. The Kaplan-Meier product-limit method was used for survival distribution, which was then analyzed with the Mantel-Cox statistic. A p less than 0.05 was used to determine significance.
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 specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY: In rats, there were no effects on clinical signs or mortality. In mice, necrotising dermatitis associated with fighting occurred in both sexes, but lead to an increase mortality in treated mice from 2 weeks to 9 months after cessation of treatment.
BODY WEIGHT AND WEIGHT GAIN: Male rats had a significant and dose-dependent decrease in body weight (table 1) during exposure, which remained lower than the controls throughout the 21-month recovery period.
HAEMATOLOGY: There were no biologically significant changes in haematology.
CLINICAL CHEMISTRY: There were no biologically significant changes in clinical chemistry.
URINALYSIS: There was a dose-dependent increase in urinary renal epithelial cell numbers in male rats (only group measured) with an increase in incidence and severity at the end of the exposure period. However, this was reversed by the after a 2 week recovery period.
ORGAN WEIGHTS: There was a significant increase in absolute and relative kidney weight in male rats at the end of the 90-day exposure period (table 1). This was not observed at the 9-month recovery period, but after a 21-month recovery period relative kidney weights were significantly increased in the low-dose group and absolute and relative kidney weights were significantly increased in the high-dose group. Kidney weights were not affected in the female rats.
HISTOPATHOLOGY: NON-NEOPLASTIC: Both male rat treatment groups developed hydrocarbon-induced nephropathy (table 2), which included exacerbated hyaline droplet formation, granular casts in the outer medulla, and increased incidence and severity of lesions undifferentiable from those of chronic progressive nephrosis. The hyaline droplet response was resolved by the 2 week recovery period and the granular casts were resolved after 9 or 21 months of recovery. However, the lesions of chronic progressive nephrosis and the linear mineralization in the inner medulla continued to increase in incidence and severity throughout the recovery period. There were no other significant histopathological findings.
HISTOPATHOLOGY: NEOPLASTIC: Although there was a slight increase in thyroid C cell adenomas in the females (14, 16, and 27% in the control, low- and high-dose group, respectively), the findings were not significant and the combined incidence for thyroid neoplasms in the control group exceeded the expected incidence for this strain and age.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 500 mg/m³ air (nominal)
- Sex:
- male
- Basis for effect level:
- other: Body weight; organ weights; and histopathology. These effects were due to alpha-2u globulin-mediated nephropathy.
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/m³ air (nominal)
- Sex:
- female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1
Body and kidney weights in male rats |
||||||
90-day exposure |
||||||
|
n |
Control |
n |
500 mg/m3 |
n |
1000 mg/m3 |
Body weight |
13 |
308 ± 5 |
15 |
293 ± 5 * |
14 |
283 ± 5 ** |
Kidney weight |
13 |
2.0 ± 0.03 |
13 |
2.5 ± 0.06 ** |
13 |
2.9 ± 0.06 ** |
Kidney/Body weight |
13 |
0.7 ± 0.01 |
13 |
0.9 ± 0.01 ** |
13 |
1.0 ± 0.02 ** |
9-month recovery |
||||||
Body weight |
10 |
416 ± 10 |
10 |
405 ± 5 |
10 |
397 ± 6 * |
Kidney weight |
10 |
2.7 ± 0.05 |
10 |
2.6 ± 0.05 |
10 |
2.8 ± 0.09 |
Kidney/Body weight |
10 |
0.6 ± 0.01 |
10 |
0.7 ± 0.01 |
10 |
0.7 ± 0.02 |
21-month recovery |
||||||
Body weight |
10 |
440 ± 9 |
10 |
370 ± 10 ** |
10 |
376 ± 9 ** |
Kidney weight |
10 |
3.2 ± 0.15 |
10 |
3.1 ± 0.16 |
10 |
3.6 ± 0.23 ** |
Kidney/Body weight |
10 |
0.7 ± 0.04 |
10 |
0.9 ± 0.06 ** |
10 |
1.0 ± 0.09 ** |
* p<0.05
** p<0.01
Table 2
Kidney histopathology in male rats (incidence and severity) |
|||||
90-day exposure |
|||||
|
Hyaline droplets |
Chronic progressive nephrosis |
Granular casts |
Linear papilla mineralization |
Urothelial hyperplasia |
Control |
100% (1.5) |
82% (0.4) |
0 |
0 |
0 |
500 mg/m3 |
100% (4) |
100% (1.1) |
100% (2) |
0 |
0 |
1000 mg/m3 |
100% (4) |
100% (2) |
100% (2.2) |
57% (0.6) |
0 |
2-week recovery |
|||||
Control |
86% (1) |
43% (0.4) |
0 |
0 |
0 |
500 mg/m3 |
100% (0.7) |
100% (0.8) |
100% (1.6) |
71% (0.7) |
0 |
1000 mg/m3 |
100% (0.7) |
100% (1.2) |
100% (2.5) |
88% (0.7) |
0 |
2-month recovery |
|||||
Control |
100% (1.0) |
83% (0.4) |
0 |
0 |
0 |
500 mg/m3 |
100% (1.0) |
100% (1) |
100% (0.5) |
86% (0.8) |
0 |
1000 mg/m3 |
100% (1.1) |
100% (1.3) |
100% (0.5) |
100% (1) |
0 |
9-month recovery |
|||||
Control |
75% (0.4) |
100% (0.6) |
0 |
0 |
0 |
500 mg/m3 |
100% (0.4) |
91% (1.3) |
14% (0.4) |
100% (1.2) |
14% |
1000 mg/m3 |
100% (0.4) |
100% (1.5) |
13% (0.4) |
100% (1.7) |
13% |
21-month recovery |
|||||
Control |
29% (0.5) |
100% (3) |
0 |
0 |
18% |
500 mg/m3 |
11% (0.4) |
100% (3.9) |
0 |
100% (2) |
78% |
1000 mg/m3 |
0 |
100% (4.7) |
0 |
100% (2.4) |
100% |
Applicant's summary and conclusion
- Conclusions:
- Male rats developed hydrocarbon-induced nephropathy and decreased body weight. Therefore, the LOAEL in male rats is 500 mg/m3. There were no significant treatment-related effects in female rats; therefore, the NOAEL in female rats is greater than or equal to 1000 mg/m3. However, effects seen in male rats were due to alpha-2u globulin-mediated nephropathy, and, as such, are not relevant to human exposure.
- Executive summary:
In a 90-day inhalation toxicity study, JP-8 jet fuel was administered to 95 male Fisher 344 rats and 75 female Fischer 344 rats per concentration by dynamic whole body exposure at concentrations of 0, 500 or 1000 mg/m3(0, 0.5, or 1.0 mg/L) for 24 hours per day, 7 days/week for a total of 90 days. At the end of the exposure period 15 rats/sex/concentration were sacrificed. The remaining animals were periodically sacrificed over a 2 year period.
The male rats developed hydrocarbon-induced nephropathy at both treatment concentrations. Male rats had decreased body weight and decreased absolute and relative kidney weight at both treatment concentrations. Female rats were unaffected by treatment. The NOAEL for male rats is difficult to establish, since potential adverse effects may be masked by male rat specific hydrocarbon nephropathy. However, based on the hydrocarbon-induced nephropathy and reduced body weights and increased kidney weights, the LOAEL in male rats is 500 mg/m3. These effects are not relevant for human exposure. The NOAEL for female rats is greater than or equal to 1000 mg/m3.
This study received a Klimisch score of 1 and is classified as reliable without restrictions because it was carried out in a method similar/equivalent to OECD TG 413.
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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