Petrolatum (petroleum), clay-treated

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

For insufficiently refined petrolatum, no additional data are required since data fulfilling the requirements for section 8.7.2 are adequate for the purpose of classification and labelling. 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.

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

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

There are no reproductive toxicity data available for petrolata. Adequate read-across data are available on structural analogies/surrogates to predict the properties of petrolata.

Insufficiently Refined Petrolatum (Carcinogenic or Unknown Feed-stock)

In accordance with section 1.1.2 of REACH Annex XI, further reproductive and development toxicity tests do not need to be conducted, on the basis that the data fulfilling the requirements for section 8.7.2 are adequate for the purpose of classification and labelling.

 Sufficiently Refined Petrolatum (Non-carcinogenic Feed-stock)

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.

A a key dermal read-across reproductive toxicity study using highly refined base oils (Schreiner et al., 1997) is 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:

No reproductive toxicity data are available for petrolata. There is one key oral read-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 key dermal 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.

Justification for selection of Effect on fertility via oral route:

Only oral reproductive toxicity study available.

Justification for selection of Effect on fertility via dermal route:

Only dermal reproductive toxicity study available.

Effects on developmental toxicity

Description of key information

There were no key developmental studies identified within the category. Consequently, two read-across developmental studies were identified, one on heavy paraffinic distillate aromatic extract and another on lubricant base oil (IP 346 < 3%).

Heavy paraffinic distillate furfural extract produced maternal, reproductive, and foetal toxicity in Sprague-Dawley rats when applied dermally.  Maternal toxicity was exhibited as vaginal discharge (dose-related), body weight decrease, reduction in thymus weight and increase in liver weight (125 mg/kg/day and higher) and aberrant haematology and serum chemistry (125 and/or 500 mg/kg/day). Evidence of potential reproductive effects was shown by an increased number of dams with resorptions and intrauterine death.  UDAE was developmentally toxic regardless of exposure duration as indicated by increased resorptions and decreased foetal body weights.  Furthermore, when exposures were increased to 1000 mg/kg/day and given only during gestation days 10 through 12, cleft palate and ossification delays were observed.  Cleft palate was considered to indicate a potential teratogenic effect of UDAE.

For the developmental study on lubricant base oil (IP 346 <3%), there were no other signs of maternal toxicity (high dose was 2000 mg/kg/day). 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 bioaccumulate 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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

4 200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Insufficiently Refined Petrolatum (Carcinogenic or Unknown Feed-stock)

No developmental toxicity studies have been reported for insufficiently refined petrolatum or similar materials. However, studies of distillate aromatic extracts can be used as a worst case assessment.

In a key read-across developmental toxicity study (Mobil Environmental and Health Science Laboratory, 1989a) a heavy paraffinic distillate aromatic extract (CAS No. 64742-04-7) was tested in a dermal study during gestation days 0 to 19 for developmental effects and maternal toxicity in the Sprague-Dawley rat. Nine groups of pregnant rats were divided in three groups: prenatal, postnatal and bioavailability groups (Mobil Environmental and Health Science Laboratory, 1990; Klimisch score=1). These groups are further described below. Bioavailability group procedures and results are not detailed here.

Prenatal groups: the undiluted test sample was applied without occlusion to the shaved skin of pregnant rats at doses of 8, 30, and125 mg/kg/day on gestation days 0-19 (15/group). An additional group received the same treatment at 500 mg/kg/day on gestation days 0-16. Initially, administration of the test sample to the 500 mg/kg/day group was also scheduled for gestation days 0-19, however treatment was discontinued after gestation day 16 because a high incidence of resorption was suspected (as indicated by a red vaginal discharge observed among rats in this group. Another prenatal group received the same treatment at 1000 mg/kg/day only on gestation days 10-12, an interval at which the developing foetus is sensitive to teratogenic insult. A group of sham treated rats served as control. Prenatal groups were sacrificed on gestation day 20.

The postnatal group was exposed under the same conditions as the prenatal group. Postnatal animals (10/group) were dosed at 0 or 125 mg/kg/day on gestation days 0-19. Postnatal groups were allowed to deliver their offspring naturally. Pups were observed on post partum day-0 for external malformations and variations and then together with their dams, sacrificed on post partum day-4.

End points examined in adults included clinical signs, body weight, food consumption, haematology and serum chemistry (only prenatal groups), liver and thymus weights, and uterine and net body weights. Foetal toxicity examinations included: resorption incidences, anomalous development (gross, skeletal and visceral abnormalities) and body weight.

Results - Prenatal Group

Prenatal groups were sacrificed on gestation day 20. All mothers were necropsied and grossly examined. Uterus and ovaries were excised and examined grossly. Numbers of corporea lutea per ovary of each pregnant animal were counted. Ovaries of non-pregnant animals were grossly examined and then discarded. Number and location of implantations, early and late resorptions and live and dead foetuses were recorded.

Maternal toxicity: Red vaginal discharge was observed in a number of pregnant animals in all exposed groups. Although authors mentioned this as being dose related, no statistics are provided.

In general animals exposed at 125 and 500 mg/kg/day consumed less food; at this dose level significant reduction in body weight gain, net body weight gain, and gravid uterine weight occurred throughout gestation. Body weight gain was also decreased at dose level of 1000 mg/kg/day. Of the haematology parameters evaluated, platelet and white blood cell counts were significantly affected in a dose related manner. Effects on 14 of 22 analyzed serum components were noted at the 125 or/and 500 mg/kg/day dose levels. Thymus weights were significantly reduced and liver weights increased at doses in excess of 30 mg/kg/day.  

Reproductive effects: Implantation was not adversely affected by treatment. The number of dams with no viable offspring was increased at dose levels from 125 mg/kg/day. Litter size was significantly lower and resorptions were significantly increased compared to controls at 125 mg/kg/day and higher. 

Foetal toxicity and development: At 30 mg/kg/day, although not statistically significant, a two-fold increase over controls in the number of resorptions was observed, which the authors considered as of biological relevance. Treatment at 125 mg/kg/day and at higher doses resulted in decreased mean foetal body weights. A statistically significant increase in the incidence of incompletely ossified skull bones in foetuses exposed in utero to 125 mg/kg/day was observed.  

When the period of exposure was restricted to gestation days 10 –12 and the dose increased to 1000 mg/kg/day, defects in costal cartilage development were significantly increased. Two of 114 foetuses evaluated were oedematous and had cleft palates. The cleft palate finding was considered by the authors to be biologically significant and evidence of a teratogenic effect, basis very low historical control incidences at theirs and other laboratories.

Results - Postnatal Group

In the postnatal group (10/group), three females were found to be not pregnant, five females reabsorbed their entire litters and one dam had only two pups, which she subsequently cannibalized. The postpartum analysis of the single viable litter of this group was not meaningful.

The NOAEL for both maternal and developmental toxicity is 30 mg/kg/day when administered dermally based on the numerous effects observed with doses of 125 mg/kg/day and greater.

Sufficiently Refined Petrolatum (Non-carcinogenic Feed-stock)

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 bioaccumulate 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. 1987) revealed no signs of maternal or developmental toxicity. Two groups of animals (50 and 25) were administered highly refined base oil by gavage at a dose of 5 mL/kg, every day during gestation days 6 to 19 inclusive. Food and water were available continuously. Animals were examined for viability and clinical effects twice daily. Body weights were recorded on days 0, 6, 10 and 20 of gestation. The NOAEL was determined to be greater than or equal to 5 mL/kg/day (approx. 4200 mg/kg bw/day).

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

Only available oral developmental toxicity study.

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

One of two available dermal developmental toxicity studies.

Toxicity to reproduction: other studies

Additional information

Insufficiently Refined Petrolatum

In accordance with section 1.1.2 of REACH Annex XI, further reproductive and development toxicity tests do not need to be conducted, on the basis that the data fulfilling the requirements for section 8.7.2 are adequate for the purpose of classification and labelling.

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 and insufficiently refined petrolatum 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. In contrast, potential developmental toxicity of insufficiently refined petrolatum may vary depending on the degree of refining severity of feedstocks and resulting PAC content in waxes.

In the absence of data for insufficiently refined petrolatum, key read-across developmental toxicity data was used from a study conducted using an untreated distillate aromatic extract. The material produced maternal, reproductive, and foetal toxicity in Sprague-Dawley rats and consequently, insufficiently refined petrolatum are classified as Repr. 2 (H361d: Suspected of damaging the unborn child) under EU CLP Regulation (EC No. 1272/2008).