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EC number: 931-250-7 | CAS number: -
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- fertility, other
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- Not reported
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study is classified as reliable without restrictions because it is an acceptable and well-documented study report.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
- Principles of method if other than guideline:
- This was a reproductive study performed in two parts. In the first part, males were treated for 70 to 90 days with 0 (1mL of distilled water), 750, 1500, or 3000 mg/kg/day of undiluted JP-8 jet fuel, then mated to untreated females (one female at a time). In the second part of the study, female rats were administered the test compound at doses of 0 (1mL of distilled water), 375, 750, or 1500 mg/kg/day undiluted JP-8 jet fuel for 90 -day prior to mating, through mating, gestation, delivery, and lactation for a total of 21 weeks.
- GLP compliance:
- yes
- Limit test:
- no
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
- Other: The fuel met the requirements of Military Specification MIL-T-83133A.
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles River Breeding Labs, Kingston, New York
- Weight at study initiation: 180 to 220 grams
- Housing: Individually, except during cohabitation (1 male with 1 female)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25 °C
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on mating procedure:
- - M/F ratio per cage: 1 to 1
- Length of cohabitation: Not reported
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): Not reported - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- Not applicable
- Duration of treatment / exposure:
- Males were treated for 70 to 90 days. Females were treated for 21 weeks.
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
Males: 750, 1500, or 3000 mg/kg/day
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
Females: 325, 750, or 1500 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- A minimum of 20 male rats per dose were used to test male fertility and a minimum of 35 female rats were used to test effects on female fertility.
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: Doses were based on a previous 90-day study.
- Positive control:
- None reported
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Not reported
- Cage side observations examined were not reported.
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations:Daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OTHER: Hematology (table 1), clinical chemistry (table 2), and urinalysis (table 3) was performed on a maximum of 10 females per treatment. In the same rats used for haematology and clinical chemistry, the brain, kidneys, liver, spleen, and ovaries were weighed. - Oestrous cyclicity (parental animals):
- Not performed
- Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
sperm count in epididymides, sperm motility, velocity, linearity, maximum and mean amplitude of lateral head displacement, beat/cross frequency, mean radius, number of circular cells, % circular cells/motile cells, % circular cells/all cells - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 5 postpartum: Four male and four female pups
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, weight gain
GROSS EXAMINATION OF DEAD PUPS:no - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals were sacrificed on day 90 of treatment (mating occurred during days 70 to 90 of treatment.
- Maternal animals: All surviving animals were sacrificed 1 day after weaning.
GROSS NECROPSY
- Gross necropsy details were not reported.
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table 4 were prepared for microscopic examination and weighed, respectively. - Postmortem examinations (offspring):
- No postmortem examinations were conducted on the offspring.
- Statistics:
- General toxicity data: an ANOVA with or without multiple comparisons
Reproductive measures: a one- or two-factor ANOVA and a post-hoc comparison of dose using two-tailed t-test with pooled error was used for continuous data; a Chi-square test of proportions followed by a Fischer's Exact test was used for categorical data - Reproductive indices:
- Pregnancy rate, gestation duration, litter size
- Offspring viability indices:
- Live and dead offspring, pup weight on postnatal days 1, 4, 7, 14, 21, and 90
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Details on results (P0)
BODY WEIGHT AND WEIGHT GAIN (PARENTAL ANIMALS): Body weights in male rats were decreased in a dose-dependent manner. Terminal body weights were approximately 545 grams, 520 grams, 475 grams, and 315 grams in the control, 750, 1500, and 3000 mg/kg/day, respectively (results were approximated from a figure). In females, body weight was only significantly reduced in the high-dose group, but the differences were not significant at terminal sacrifice. The body weight in females at 20 weeks (1 week before sacrifice) was approximately 400 grams, 385 grams, 382 grams, and 335 grams in the control, 375, 750, and 1500 mg/kg/day, respectively.
HAEMATOLOGY (PARENTAL ANIMALS): Haematology was not measured in the males and no effects were noted in the females.
CLINICAL CHEMISTRY (PARENTAL ANIMALS): Clinical chemistry was not measured in the males and no effects were noted in the females.
URINALYSIS (PARENTAL ANIMALS): Urinalysis was not measured in the males and no effects were noted in the females.
ORGAN WEIGHTS (PARENTAL ANIMALS): Absolute and relative liver weights were increased in mid- and high-dose females (Table 5), but were not accompanied by any histological findings.
HISTOPATHOLOGY (PARENTAL ANIMALS): The test compound caused perianal dermatitis (high-dose only) and stomach hyperplasia (mid- and high-dose) in the female rats (Table 6).
OTHER FINDINGS (PARENTAL ANIMALS): There were no treatment-related effects on reproduction or sperm parameters in males. There were no effects on reproduction, gestation, or litter size in females.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 750 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: body weight
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction
- Effect level:
- >= 3 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: duration of pregnancy; pregnancy rate; sperm characterization
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction
- Effect level:
- >= 1 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: duration of pregnancy; live birth index; pregnancy rate; litter size; litter weight
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
Details on results (F1)
BODY WEIGHT (OFFSPRING): There was a dose-related decrease in pup weight that was significant in the 750 mg/kg/day group on postnatal day 4 only and in the 1500 mg/kg/day group from postnatal day 4 through postnatal day 21 but had recovered by postnatal day 90.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 750 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: pup weight
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
The decreased body weight in males was probably related to nephropathy that is typically produced in male rats exposed to hydrocarbon fuels. Although there were changes in liver weight in the females, this was not accompanied by any changes in clinical chemistry or liver histopathology so is likely not of biological significance. | ||||
Table 5 | ||||
Body weight and liver weights in female rats | ||||
Control | 325 mg/kg/day | 750 mg/kg/day | 1500 mg/kg/day | |
n=10 | n=7 | n=8 | n=8 | |
Terminal Body weight | 351.0 ± 12.6 | 354.3 ± 9.0 | 357.5 ± 6.5 | 348.8 ± 16.3 |
Absolute liver weight | 14.8 ± 0.8 | 15.7 ± 0.6 | 17.8 ± 0.7 * | 19.1 ± 0.7 ** |
Liver to body weight | 4.2 ± 0.1 | 4.4 ± 0.1 | 5.0 ± 0.2 ** | 5.5 ± 0.1 ** |
Liver to brain weight | 754.9 ±38.9 | 823.6 ± 39.8 | 903.1 ± 31.8 * | 993.6 ± 46.3 ** |
* p<0.05 | ||||
** p<0.01 | ||||
Table 6 | ||||
Incidence and severity significant histopathological findings in female rats | ||||
Control | 325 mg/kg/day | 750 mg/kg/day | 1500 mg/kg/day | |
n=8 | n=4 | n=5 | n=6 | |
Perianal dermatitis | 0 | 0 | 0 | 83% (1.2) * |
Anal hyperplasia | 0 | 0 | 0 | 50% (0.7) |
Stomach gastritis | 0 | 50% (0.5) | 20% (0.2) | 0 |
Stomach hyperplasia | 0 | 75% (0.8) | 100% (1.6) * | 100% (1.7) * |
* p<0.05 |
Applicant's summary and conclusion
- Conclusions:
- The study LOAEL for systemic effects is 1500 mg/kg/day and the NOAEL for systemic effects is 750 mg/kg/day, based on reduced body weight in dams and in pups. The LOAEL for adult males rats exposed to JP-8 orally was 750 mg/kg/day due to changes in clinical pathology, body weight, organ weights and the same irritation seen in female rats. The reproduction NOAEL was 3000 and 1500 mg/kg/day in males and females, respectively.
- Executive summary:
This was a reproductive study performed in two parts. In the first part, males were treated for 70 to 90 days with 0 (1mL of distilled water), 750, 1500, or 3000 mg/kg/day of undiluted JP-8 jet fuel, then mated to untreated females (one female at a time). Males were gavaged throughout the cohabitation period and were returned to their individual cage after successful mating. In the second part of the study, female rats were administered the test compound at doses of 0 (1mL of distilled water), 375, 750, or 1500 mg/kg/day undiluted JP-8 jet fuel for 90 -day prior to mating, through mating, gestation, delivery, and lactation for a total of 21 week. During mating, they were housed with untreated males. Litters were standardized to 4 male pups and 4 female pups on postnatal day 5. Although those pups were used for neurobehavioral tests, the data was not provided in the study report.
There were no effects on clinical signs or mortality in either sex. Haematology, clinical chemistry, and urinalysis were measured only in females without any effects noted. Body weights in male rats were decreased in a dose-dependent manner and was likely related to nephropathy that is specific in male rats treated with hydrocarbons. In females, body weight was only significantly reduced in the high-dose group. Absolute and relative liver weights were increased in mid- and high-dose females, but were not likely biologically significant due to the lack of changes in clinical chemistry or histopathology in the liver. The test compound caused perianal dermatitis (high-dose only) and stomach hyperplasia (mid- and high-dose) in the female rats (histopathology was not conducted on the males for this study because previous studies have indicated nephropathy). There were no treatment-related effects on reproduction or sperm parameters in males. There were no effects on reproduction, gestation, or litter size in females. There was a dose-related decrease in pup weight that was significant in the 750 mg/kg/day group on postnatal day 4 only and in the 1500 mg/kg/day group from postnatal day 4 through postnatal day 21 but had recovered by postnatal day 90.
The study LOAEL for systemic effects is 1500 mg/kg/day and the NOAEL for systemic effects is 750 mg/kg/day, based on reduced body weight in dams and in pups. The LOAEL for adult males rats exposed to JP-8 orally was 750 mg/kg/day due to changes in clinical pathology, body weight, organ weights and the same irritation seen in female rats.Changes in male rats may be complicated by the male rat-specific nephropathy produced after exposure to hydrocarbon fuels such as JP-4 and JP-8. The reproduction NOAEL was 3000 and 1500 mg/kg/day in males and females, respectively.
This study received a Klimisch score of 1 and is classified as reliable without restrictions because it is an acceptable and well-documented study report.
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