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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Additional information

In a key one-generation reproductive toxicity study, rats were administered test material dermally at doses of 0, 125, 500, or 2000 mg/kg throughout the premating period (ca. 10 weeks, 5 days/week), the mating period (ca. 3 weeks, 5 days/week), and the postmating period (ca. 9 weeks postmating) (Klimisch score = 2; Mobil 1987). No mortality was observed in any treatment groups. No treatment-related changes in body weight gain or food consumption were observed in the females of the parental generation. No adverse effects were noted in the number of implantation sites per dam, litter size, or length of gestation in treated animals. Treatment-related clinical signs included erythema, scabs, and flaking at application site at all dose levels. No signs of gross toxicity were observed at necropsy. The parental systemic NOAEL is greater than or equal to 2000 mg/kg bw/day for females. Data on males were not provided in this study report. The offspring exhibited no significant differences in body weight gain, eyelid disjunction, righting reflex, or viability in treated groups versus control.  No treatment-related signs of gross pathology were noted at necropsy. The offspring NOAEL is greater than or equal to 2000 mg/kg bw/day.

Highly refined base oil was used as a vehicle control group in a key dermal application study reported by Schreiner et al. (1997; Klimisch score = 1) to determine the potential reproductive effects of kerosene. The study, classified as supporting, 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). 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/fertility was 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. Based on these results, the NOAEL for overall effects for reproductive endpoints was greater than or equal to 1000 mg/kg bw/day.

In a key read across reproduction/developmental screening study (WIL, 1995; Klimisch score = 1), a sufficiently refined lubricant base oil (IP 346 < 3%) was administered by gavage at a dose of 1000 mg/kg (bw) to a group of 12 male and 12 female Sprague-Dawley rats. Information from studies on other lubricant base oils may be used as surrogates since they are less-refined than highly refined base oils and will therefore represent a worst case.  Compositional and physico-chemical data also show that highly refined base oils are very similar to other lubricant base oils, and it is therefore considered appropriate to read across from the other lubricant base oils data to highly refined base oils.  There were no clinical findings and growth rates and food consumption values were normal. Fertility indices and mating indices for males and females were both 100%. At necropsy, there were no consistent findings, and the animals were considered to be normal. Organ weights and histopathology were considered normal. The NOAEL for this study was greater than or equal to 1000 mg/kg/day.

White oil administered to male and female rats via oral gavage at a dose of5 mL/Kg, 5 days a week for 13 weeks did not cause any reproductive toxicity (McKee et al., 1987; Klimisch score = 2).

 

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 was greater than or equal to 1000 mg/kg/day and no LOAEL was determined.

In accordance with Section 1 of REACH Annex XI, additional reproductive toxicity studies do not appear to be scientifically necessary, as two developmental/reproductive toxicity studies conducted under internationally agreed validation principles provided no indication that white mineral oils have adverse reproductive effects. Further, no adverse effects on reproductive organs have been noted in multiple oral and dermal repeat dose studies or in carcinogenesis bioassays.

Short description of key information:

Highly refined base oil was not found to be a reproductive toxicant (OECD 421).  The NOAEL for oral exposure is greater than or equal to 1000 mg/kg bw/day and the NOAEL for dermal exposure is greater than or equal to 2000 mg/kg bw/day.  

Justification for selection of Effect on fertility via oral route:

Only one oral reproductive toxicity study available

Justification for selection of Effect on fertility via dermal route:

One of two dermal reproductive toxicity studies

Effects on developmental toxicity

Description of key information

Highly refined base oil was not found to be a developmental toxicant (OECD 414).  The NOAEL for oral exposure is greater than or equal to 5000 mg/kg bw/day, the NOAEL for dermal exposure is greater than or equal to 2000 mg/kg bw/day, and the NOAEC for inhalation exposure is greater than or equal to 1000 mg/m3.  

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
1 000 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Additional information

In a developmental study, presumed-pregnant animals were exposed to white mineral oil at the maximum dose that could be administered via multiple routes: dermal application of 2000 mg/kg bw/day; inhalation exposure of 1000 mg/m3, and ingestion of 5000 mg/kg bw/day (Klimisch score =2; Mobil 1987). No adverse effects were noted on reproductive parameters or on the in utero survival or development of the offspring. The developmental NOAEL is greater than or equal to 2000 mg/kg (dermal), greater than or equal to 1000 mg/m3 (inhalation), and greater than or equal to 5000 mg/kg (oral), the highest dose tested for each route.

In a supporting study, (Klimisch score = 2; McKee et al. 1987) white oil was used as the solvent control for two test materials. Two groups of animals (50 and 25) were administered white oil by gavage at a dose of 5 mL/kg/day, every day during gestation days 6 to 19 inclusive.

In the control group containing 50 animals, 3 malformed foetuses were found in 3 litters; one had an extra lumbar vertebra, one had a discrete area of ossification in the area of the junction of the frontal and nasal bones, and one had moderately dilated lateral ventricles of the brain. Three malformed foetuses were also found in 3 litters of the other control group. These were a vertebral arterial canal of a cervical process fully ossified in 2 foetuses and angulated ribs in a third foetus. The authors considered these malformations to be minor and that the findings were within the normal ranges for the strain of rat. Therefore, the NOAEL is greater than or equal to 5 mL/kg/day (approx. 4200 mg/kg bw/day).

 

In a developmental toxicity study, white oil (Stock 461) was administered to 20 (treated) or 21 (control) female Sprague-Dawley rats/dose dermally at dose levels of 0 or 2000 mg/kg bw/day from days 6 through 19 of gestation. There was no maternal toxicity observed at 2000 mg/kg/day. Consequently, the maternalNOAEL is greater than or equal to 2000 mg/kg/day. There was no developmental toxicity observed at 2000 mg/kg/day. Consequently, the developmental NOAEL is greater than or equal to 2000 mg/kg/day.

 

 

Justification for selection of Effect on developmental toxicity: via oral route:

One of two oral developmental toxicity studies

Justification for selection of Effect on developmental toxicity: via inhalation route:

Only inhalation developmental toxicity study

Justification for selection of Effect on developmental toxicity: via dermal route:

Only dermal developmental study.

Justification for classification or non-classification

Reproductive toxicity studies did not provide sufficient evidence to cause a strong suspicion of impaired fertility in the absence of toxic effects. Therefore, there is insufficient data to classify highly refined base oils as toxic for reproduction under Annex I of EU CLP Regulation (EC No. 1272/2008).

Developmental studies did not provide sufficient evidence to cause a strong suspicion of developmental toxicity in the absence of signs of marked maternal toxicity, therefore highly refined base oils are not classified as a developmental toxicant according to Annex I of EU CLP Regulation (EC No. 1272/2008).