Lubricating oils, used

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

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 sufficiently refined lubricant base oils (IP 346< 3 wt%) have adverse reproductive effects. Further no adverse effects on reproductive organs have been noted in multiple dermal or inhalation repeat dose studies (28-day) or carcinogenesis bioassays.

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

In a key reproduction/developmental screening study (WIL Research Laboratories, 1995), 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. Rats designated F₀animals were dosed for a minimum of 14 days prior to mating. Dosing was continued after mating until a total dosing period of 30 days had elapsed for males and until day 4 of lactation for females (39 days). The animals were observed twice daily for appearance, behaviour, morbidity and mortality. Males and females were also observed during dosing and for one hour thereafter. Male F₀body weights were recorded weekly. Female F₀body weights were also recorded weekly until evidence of mating was observed and then on gestation days 0, 7, 14 and 20 and on lactation days 1 and 4. Food consumption was also recorded for F₀(both sexes). Animals were paired on a 1:1 basis. Positive evidence of mating was confirmed either by the presence of sperm in a vaginal smear or a vaginal plug. The day when evidence of mating was identified was termed Day 0 of gestation.

 

The following fertility indices were calculated: Female mating index; Male mating index; Female fertility index; and Male fertility index. All females were allowed to deliver their young naturally and rear them to post-natal day 4. Females were observed twice daily during the period of expected parturition for initiation and completion of parturition and for signs of dystocia. After parturition, litters were sexed and examined for evidence of gross malformations, numbers of stillborn and live pups. Litters were examined daily, and each pup received a detailed physical examination on days 1 and 4 of lactation. All abnormalities were recorded. The live litter size and viability index were calculated. All surviving pups were necropsied on post-natal day 4. A complete gross examination was made on all animals at necropsy. Selected organs of parental animals were weighed, and a wide range of tissues were fixed for subsequent histopathological examination.

 

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 ≥1000 mg/kg/day.

In a key read-across reproductive toxicity study (Schreiner et al.1997) highly refined mineral oils (highly refined base oils) were tested in Sprague-Dawley rats. Highly refined base oils are similar in composition to other lubricant base oils, and hence similar effects would be expected.

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 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/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.

Short description of key information:

Two key screening reproductive/developmental studies (OECD 421) were identified.  No reproductive or developmental effects were observed in Sprague-Dawley rats.

Effects on developmental toxicity

Description of key information

For sufficiently refined other lubricant base oils (IP 346 < 3%), one key developmental study (OECD 414) was identified.  The study was conducted dermally with Sprague-Dawley rats.  A maternal LOAEL was not reported but can be referenced to be 125 mg/kg/day based on skin irritation.  A developmental/teratogenic NOAEL was not reported; however, it can be inferred that this value is 2000 mg/kg/day.

Effect on developmental toxicity: via dermal route

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Additional information

One key developmental study (Mobil Environmental and Health Science Laboratory, 1987) on sufficiently refined other lubricant base oils was identified. In this study, 100 SUS solvent refined base oil was administered to female Sprague Dawley rats dermally. There were five dose groups. Groups 2 through 4 (10 dams/group in Groups 2 and 3; 15 dams/group in Group 4) were administered 125, 500, 2000 mg/kg/day using a 1 cc syringe (calibrated in 0.01 cc). Dams were clipped on the dorsal surface, and the test material was dispensed evenly over the test site. Animals were fitted with Elizabethan-style collars. The control group (Group 1; 15 dams/group) was clipped and collared in a similar fashion. For the control group, the dorsal skin of each rat was stroked with the tip of a 1 cc syringe, but no test material was applied. A fifth dose group (5 dams/group) was used, in which dams were applied the base oil on gestation day 0-17 at a dose level of 2000 mg/kg/day. A base oil fortified with [1-14C]octacosane was administered on gestation day 18.

Dermal application of the lubricant base oil to pregnant rats during gestation produced slight dermal irritation at all dose levels. At these dosages, the lubricant base oil produced erythema and flaking of the skin at the site of application in a dose-dependent manner. One animal in the 500 mg/kg/day dose group had dermal oedema.There were no other signs of maternal toxicity. Serum components were not adversely affected by the test material. According to the Group 5 results, the test material metabolites were able to pass across the placenta, but did not bioacculmulate in the foetuses. Maternal LOAEL was 125 mg/kg/day based on skin irritation. There was no evidence of teratogenicity. There were no treatment-related changes observed during the external, skeletal, or visceral evaluations. Mean foetal weight and crown-rump lengths were comparable across all dose groups. Developmental/teratogenic NOAEL was 2000 mg/kg/day.

Justification for classification or non-classification

A key screening reproductive/developmental toxicity study on sufficiently refined other lubricant base oils showed no effects on reproductive parameters. Sufficiently refined other lubricant base oils do not meet the EU criteria for reproductive toxicity and are not classified under Annex VI of EU Dangerous Substances Directive 67/584/EEC.

Developmental toxicity studies conducted using sufficiently refined other lubricant base oils (IP 346 < 3%) did not reveal any treatment-related teratogenic effects. Sufficiently refined other lubricant base oils do not meet the EU criteria for developmental toxicity and are not classified.