Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data identified.

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 study available
Additional information

Justification for Read Across

This substance is similar to the feedstocks for most of current dewaxing operations that produce the finished paraffin and microcrystalline waxes. These lubricant base oil data may serve as the basis for a worst case assessment of the reproductive potential of paraffin and microcrystalline waxes and are summarised in this section.

In a key read-across reproduction/developmental screening study (WIL, 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.

Short description of key information:

One read-across screening reproductive/developmental study (OECD 421) was identified.  No reproductive or developmental effects were observed in rats.

Effects on developmental toxicity

Description of key information

A read-across dermal developmental study (OECD 414) was identified (Mobil Environmental and Health Science Laboratory, 1987). There were no treatment-related changes observed during the external, skeletal, or visceral evaluations in the rat foetuses. 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 study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Study duration:
subchronic
Species:
rat
Additional information

Justification for Read Across

This substance is similar to the feedstocks for most of current dewaxing operations that produce the finished paraffin and microcrystalline waxes. These lubricant base oil data may serve as the basis for a worst case assessment of the reproductive potential of paraffin and microcrystalline waxes and are summarised in this section.

One key read-across developmental toxicity study (Klimisch score=1) was identified, in which 100 SUS solvent refined base oil was administered to female Sprague Dawley rats dermally (Mobil Environmental and Health Science Laboratory, 1987). This substance is similar to the feedstocks for most of current dewaxing operations that produce the finished paraffin and microcrystalline waxes. These lubricant base oil data may serve as the basis for a worst case assessment of the reproductive potential of paraffin and microcrystalline waxes and are summarised in this section.

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 treated with 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.

Justification for classification or non-classification

No two -generation reproductive toxicity data are available for paraffin and hydrocarbon waxes. A read-across screening reproductive/developmental toxicity study showed no effects on reproductive parameters. A read-across developmental toxicity study showed no teratogenic effects. Although results from these studies showed no reproductive or developmental effects at the highest dose tested, these study results cannot be substituted for results from a complete two-generation reproductive study as required under REACH. There is insufficient data to classify paraffin and hydrocarbon wax as toxic for reproduction under Annex VI of EU CLP Regulation (EC No. 1272/2008).