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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP status unknown, near-guideline study, published in peer reviewed literature, restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference
Reference Type:
publication
Title:
Assessment of the potential reproductive and subchronic toxicity of EDS coal liquids in Sprague-Dawley rats
Author:
McKee RH, Plutnick RT and Traul KA
Year:
1987
Bibliographic source:
Toxicology, 46, 267-280

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
yes
Remarks:
limited parameters assessed and females not dosed during gestation or lactation
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): experimental fuel oil (nominal boiling range 200-538°C)
- Substance type: liquid fuel from coal
- Physical state: liquid
- Composition of test material, percentage of components: 70/30 (w/w) blend of recycle solvent and vacuum gas oil (nominal boiling range 427-538°C), composition as follows: carbon 88%, hydrogen 10%, oxygen 1.5%, nitrogen 0.24%, sulphur 0.34%; saturates 36%, aromatics 64%;
- Distillation curve: 5 wt% 181°C, 50 wt% 299°C, 95 wt% 657°C
- Specific gravity: 11.6 °API
- Flash point: 107 °C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Laboratory Animals, Scottdale, PA, USA
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: not reported
- Fasting period before study: no
- Housing: stainless steel cages
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 40-70%
- Air changes (per hr): no data
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: highly refined white oil (CAS No 8012-95-1)
Details on exposure:
Doses were approximately 20, 100 and 500 mg/kg body weight/day based on the most current bodyweight. Dose volume: 5 mL/kg bodyweight. Control 5mL/kg white oil only.
Details on mating procedure:
- M/F ratio per cage: 1:2
- Length of cohabitation: 10 consecutive nights or until mating confirmed
- Proof of pregnancy: copulatory plug / sperm in vaginal rinse referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): no details reported
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks pre-mating
Frequency of treatment:
5 times/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 20, 100, 500 mg/kg bw
Basis:
other: nominal in white oil
No. of animals per sex per dose:
72 females and 36 males for controls, 36 females and 18 males for treatment groups
Control animals:
yes, concurrent vehicle
Details on study design:
Rats were randomly distributed to treatment groups using a selection system based on bodyweight

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: mated females days 0, 7, 14 and 21 of gestation and days 0, 7, 14 and 21 of lactation

BODY WEIGHT: Yes
- Time schedule for examinations: males and females: prior to dosing (day 0), weekly during the 13 week dosing period; mated females only: days 0, 7, 14 and 21 of gestation and days 0, 7, 14 and 21 of lactation

FOOD CONSUMPTION: No

WATER CONSUMPTION: No
Oestrous cyclicity (parental animals):
no
Sperm parameters (parental animals):
no
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED: All pups given gross physical examination and weighed on days 0, 4, 14 and 21 of lactation
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: following confirmation of mating, males were killed to evaluate subchronic toxicity (results are presented in section 7.5.1)
- Maternal animals: day 21 of lactation

GROSS NECROPSY: Yes, all dams

HISTOPATHOLOGY / ORGAN WEIGHTS: no
Postmortem examinations (offspring):
SACRIFICE AND GROSS NECROPSY:
- The F1 offspring were killed on day 21 of lactation, necropsied and visceral organs and brains examined. Any pups that died prior to day 21 were also necropsied (unless cannibalised or autolysed)

HISTOPATHOLOGY / ORGAN WEIGHTS: no
Statistics:
Bartlett's test of homogeneity of variance (at 1% level of significance), followed by standard one-way analysis of variance or Duncan's test plus a linear regression. Armitage test for linear trend. Standard nested analysis of variance. Least significant difference technique.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed

Reproductive function / performance (P0)

Reproductive performance:
no effects observed

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): No effects on general condition of dams during the lactation period.


BODY WEIGHT (PARENTAL ANIMALS): There were no treatement related effects.


REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): There were no effects on pregnancy rate, no significant differences in frequency of fertilisation and implantation, length of gestation period or maternal weight gain during gestation.


GROSS PATHOLOGY (PARENTAL ANIMALS) : No abnormalities seen at gross necropsy.


Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: no effects on pregnancy rate, gestation period or maternal weight gain during gestation, no effects on mean litter size at highest dose tested

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Gross pathological findings:
no effects observed

Details on results (F1)

No effect on mean litter size, number of live births, survival during lactation period, pup weight gain or clinical condition of pups. Gross necropsy of pups showed no increase in the overall incidence of abnormalities or the incidence of any specific abnormalities.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
500 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: no evidence of reproductive toxicity at highest dose tested

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
EDS fuel oil showed no effects on fertility in rats following 13 weeks of oral dosing pror to mating. The NOAEL for reproductive toxicity was 500 mg/kg bw/day.
Executive summary:

EDS fuel oil (nominal boiling range 200-538°C) was investigated for reproductive toxicity in Sprague-Dawley rats. Animals were dosed by gavage at 0, 20, 100 or 500 mg/kg 5 days/week for 13 weeks prior to mating. Resulting pregnant females were allowed to litter and then dams and pups were killed on day 21 of lactation.

There were no effects on pregnancy rate, no significant differences in frequency of fertilisation and implantation, length of gestation period or maternal weight gain during gestation. The NOAEL for reproductive toxicity was 500 mg/kg bw/day.