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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
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 was conducted according to OECD 421 guidelines.

Data source

Reference
Reference Type:
publication
Title:
Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of hydrodesulfurized kerosine
Author:
Schreiner, C., Bui, Q., Breglia, R., Burnett, D., Koschier, F., Podhasky, P., Lapadula, L., White, R., Feuston, M., Krueger, A., Rodriquez, S.
Year:
1997
Bibliographic source:
Journal of Toxicology and Environmental Health 52:211-229

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Read Across to Highly Refined Base Oils
- Name of test material (as cited in study report): Squibb (340 SUS)
- Substance type: Highly Refined Base Oil

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
dermal
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
Approximately 7 weeks in females and 8 weeks in males
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1 mL/kg/day
Basis:
other: amount applied
No. of animals per sex per dose:
Ten animals per sex per treatment
Control animals:
yes, sham-exposed

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
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks:
Reproductive
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: overall effects

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined

Effect levels (F1)

Dose descriptor:
NOAEL
Remarks:
developmental
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: overall effects

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Squibb (340 SUS) mineral oil (a white mineral oil) caused no reproductive or developmental toxicity with 1 mL/kg/day (i.e., 1000 mg/kg/day) in an OECD 421 guideline study, but did cause mild to moderate skin irritation. Therefore, the reproductive/developmental NOAEL for this study is ≥1000 mg/kg/day and no LOAEL was determined.
Executive summary:

Read Across Justification

In this study a highly refined mineral oil (highly refined base oil) was tested, but being similar in composition to other lubricant base oils, similar properties would be expected.

White oil was used as a vehicle control group in a dermal application study reported by Schreiner et al. (1997) to determine the potential reproductive effects of kerosene. The study employed a sham-treated control and a group in which white oil Squibb (340 SUS) mineral oil was administered at a dose of 1 ml/kg/day (approximately 1000 mg/kg/day). Only the results of the sham-treated control group and the group given white mineral oil are summarised below. The study was performed in accordance with OECD guideline 421 with the addition that males were treated for 8 weeks to assess possible effects on the reproductive system. Also females were weighed 7 times during gestation rather than 4, and at necropsy, 7 organs in addition to the reproductive organs were weighed. Ten approximately eight week old male Sprague-Dawley rats (275 to 285 grams) and 10 females of the same age (183 to 187 grams) per test group were treated dermally. Doses were selected on the basis of the results of a preliminary 2-week range finding study. There were two control groups: the vehicle control was given mineral oil only at a rate of 1 ml/kg/day (approximately 1000 mg/kg/day) and, in the sham-treated group, the animals were fitted with collars and were stroked with the tip of a syringe, but no material was applied. Test material or mineral oil was applied daily to the shorn skin of the animals 7 days/week from 14 days pre-mating, during 14 days mating and through 20 days of gestation. Collars were fitted to the animals during the dosing period to prevent ingestion of applied materials. After the final dose, the collars were removed and residual test material was wiped from the skin. Males were treated through gestation until final female sacrifice on days 4 to 6 of lactation.

 

During the mating period the test material remained on the backs of the animals for 6 hours. Prior to pairing, the test material was removed by wiping. Rats were mated overnight on a 1:1 ratio and were separated the following morning. Collars were then applied prior to the next dose being applied. Females were monitored for evidence that mating had taken place. Pregnancy was determined by the presence of a vaginal plug or sperm in a vaginal lavage sample. If observed, the female was considered to be at day 0 of gestation. Any female that did not show evidence of mating was placed with the same male the following evening. Any female that did not show evidence of mating at the end of a 2 week mating period was presumed pregnant (gestation day 0 = last day of co-habitation).

 

Animals were checked twice daily for morbidity and mortality during weekdays but only once daily at weekends. Animals were also observed immediately prior to dosing and after the last animal had been dosed for appearance, behaviour and motor activity, respiratory function, central nervous system function, excretory function and biological discharges. Effects of test material on the skin were assessed and scored weekly using Draize scales for erythema and oedema and for chronic deterioration. Males were weighed on the first day of dosing, then weekly and on the day of sacrifice. Females were also weighed on the first day of dosing, then weekly until mating was confirmed and thereafter on gestation days 0, 3, 6, 10, 13, 16 and 20 and on post partum days 0 and 4. Food consumption was also monitored on a similar schedule except through the mating period. Each presumed-pregnant female was observed daily from gestation day 20 for parturition; evidence of dystocia was noted. The day of delivery was designated postpartum day 0. Maternal behaviour and appearance were monitored daily until sacrifice. Each litter was examined as soon as possible after birth to establish the number and sex of pups, stillbirths, live births and the presence of gross abnormalities. Pups were examined daily for presence of milk in their stomachs. Any pup found dead was examined externally and unusual findings were recorded. The body weight of each viable offspring was individually measured and recorded on post partum days 1 and 4.

 

Adult females that did not deliver were sacrificed on day 25 of gestation. Dams that delivered and maintained their litters until post partum day 4 were sacrificed with their offspring on post-partum days 4 to 6. All males were sacrificed after the females had been killed. All animals were examined macroscopically for structural anomalies and pathological changes, with emphasis on the reproductive organs. The numbers of implantation sites and corpora lutea of each adult female were recorded. No tissues from offspring were retained. The liver, kidneys, adrenals, thymus, spleen, brain and heart of all parental animals were weighed. In addition the testes and epidymides of parental males were weighed. Skin from treated sites, ovaries and testes and epididymides were prepared for histological examination. Pathological evaluation was performed on reproductive organs from all males and pregnant females in both control groups and the high dose group and on treated skin from all groups.

 

No animals died or were prematurely sacrificed and no clinical signs of toxicity were observed. Skin irritation among males varied from slight to moderate with increasing dose and was most severe in the high dose group. Mild to moderate skin irritation was observed in females at the highest concentration. At terminal sacrifice, no findings were reported except for those on the skin. Microscopic changes were found in the skin of vehicle control and all kerosine-treated groups in the males. In females changes were only observed in the high dose group animals. A mean dermal irritation score of 1.3 (maximum of 3) was observed.Body weights were unaffected by treatment. Reproductive/fertilitywas unaffected by treatment. No test-material-related microscopic changes were observed in the testes or epididymides of adult male rats or in the ovaries of adult female rats.

Squibb (340 SUS) mineral oil (a white mineral oil) caused no reproductive or developmental toxicity with 1 mL/kg/day (i.e., 1000 mg/kg/day) in an OECD 421 guideline study, but did cause mild to moderate skin irritation. Therefore, the reproductive/developmental NOAEL for this study is 1000 mg/kg/day and no LOAEL was determined.