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Effects on fertility

Description of key information
 For sufficiently refined petrolatum additional studies do not appear to be necessary since data available from reproductive/developmental toxicity studies and repeat dose carcinogenic bioassays (oral and dermal) indicate no adverse reproductive effects.
Additional information

Sufficiently Refined Petrolatum

 

No reproductive studies have been reported for sufficiently refined petrolatum or constituents of these materials, but such studies have been reported for other lubricant base oils and as the basis for a worst case are summarised in this section.

 

In a key read-across reproductive toxicity screening study (WIL Research Laboratories, 1995) carried out according to OECD Guideline 421, a lubricant base oil (IP 346 < 3 wt%; CAS No. 64742-54-7) was administered by gavage at a dose of 1150 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.

 

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 1150 mg/kg/day.

 

Supporting data from reproductive toxicity studies using highly refined base oils (Schreiner et al., 1997) are available. A highly refined base oil (CAS No. 8042 -47 -5) has been shown to cause no reproductive or developmental toxicity in rats dosed dermally with 1 mL/kg/day (i. e., 1000 mg/kg/day). The reproductive/developmental NOAEL for this study is 1000 mg/kg/day and no LOAEL was determined.


Short description of key information:
There is one key-across study (WIL, 1995) identified that was performed according to or similarly to OECD 421. For this study conducted with lubricant base oil (IP 346<3 wt%), reproductive performance was not adversely affected at any dose level evaluated; consequently, the reproductive NOAEL can be inferred as 1150 mg/kg/day.

A supporting study (Schreiner et al., 1997) on highly refined base oils indicates that they cause no reproductive or developmental toxicity in rats dosed dermally with 1 mL/kg/day (i.e., 1000 mg/kg/day). The reproductive/developmental NOAEL for this study is 1000 mg/kg/day and no LOAEL was determined.

Effects on developmental toxicity

Additional information

Sufficiently Refined Petrolatum

 

No developmental toxicity studies have been reported for sufficiently refined petrolatum and constituents of these materials, paraffin and hydrocarbon waxes, but a study has been reported for lubricant base oils, materials similar to the feed to most of current dewaxing operations.

 

In a key read-across developmental toxicity study (Mobil Environmental and Health Science Laboratory, 1987b), a solvent refined lubricant base oil (IP 346 < 3 wt%) was administered to female Sprague Dawley rats dermally. There were five dose group. 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. A maternal LOAEL was not reported but can be inferred to be 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. A developmental/teratogenic NOAEL was not reported; however, it can be inferred that this value is 2000 mg/kg/day.

 

Supporting data from studies conducted using highly refined base oils (McKee et al. 1987b) revealed no signs of maternal or developmental toxicity.

Toxicity to reproduction: other studies

Additional information

Sufficiently Refined Petrolatum

 

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 other 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.

Justification for classification or non-classification

No 2 -generation reproductive toxicity data are available for petrolatum. This study type is a data requirement for REACH. Two key read-across screening reproductive/developmental toxicity studies showed no effects on reproductive parameters. There is insufficient data to classify sufficiently refined as toxic for reproduction/fertility the new Regulation (EC) 1272/2008 on classification, labelling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances.

 

The potential developmental toxicity of petrolatums is expected to be associated with the biologically available/active impurities such as polycyclic aromatic constituents (PAC) found in the entrained oil of the wax material. Severely refined petrolatums, produced from highly refined feedstocks which contain significantly reduced amount of PAC and other impurities, are not expected to be developmentally toxic.  

Additional information