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Administrative data

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 the unrefined acid-treated oils are classified as carcinogenic, category 1A and toxic to reproduction, category 2 (H361d); the latter is based on read-across to a related material.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Short description of key information:

In accordance with Section 1 of REACH Annex XI, fertility toxicity studies do not appear to be scientifically necessary, as the unrefined acid-treated oils are classified as carcinogenic, category 1A and toxic to reproduction, category 2; the latter is based on read-across to a related material.

Effects on developmental toxicity

Description of key information

A read-across dermal developmental study (OECD 414) was identified.  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.

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:
adverse effect observed
Dose descriptor:
NOAEL
30 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Additional information

A related material , heavy paraffinic distillate aromatic extract (CAS# 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 (Mobil, 1990b). Nine groups of pregnant rats were divided in three groups: prenatal, postnatal and bioavailability groups. With the exception of the bioavailability group, results are further described below.

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 corpora 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 twofold increase over controls in the number of resorptions was observed, which the authors considered as of biological relevance. However, reanalysis of the data using the litter as the statistical unit (rather than individual resorptions) identifies30 mg/kg bw/day as the appropriate NOAEL for developmental toxicity. 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, based on 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 resorbed 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.

Justification for Read Across

 

DAE is produced as a by product in the refining of lubricating oil base stocks and waxes. Straight run vacuum distillates (lubricant base stocks) are extracted with solvents such as furfural, phenol, or N-methyl-2-pyrrolidone to selectively remove the undesirable polycyclic aromatic compounds, (especially 3-7 fused ring structures). DAE can be considered “worst case” by comparison to unrefined / acid treated oils, in that the extract contains higher concentrations of biologically active components than the unrefined / acid treated oils.

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

Read-across to a related material

Justification for classification or non-classification

No two -generation reproductive toxicity data are available for unrefined/acid treated oils; however, according to REACH Annex X, 8.7, a reproductive study is not needed as substances in this category are classified as carcinogenic Category 1. A read-across developmental toxicity study was conducted on distillate aromatic extract to illustrate a worst-case scenario. Based on the study results, unrefined/acid treated oils are classified as a Reproductive Toxicity Category 2 (H361d) under the EU CLP Regulation (EC No. 1272/2008).