Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No other concerns identified.
Additional information

The following two studies were identified: a 91-day study which assessed the systemic toxicological effects of treatment with 1 -decene, homopolymer, hydrogenated (Ethylflo 166) on rats previously treated in utero with the same chemical; and a 90-day study with Alkane 4 (a structural analogue) which assessed fertility and developmental effects in a one-generation study (OECD 415). Details of the studies are presented below.

In a one-generation reproduction study, Ethylflo 166 (a 1 -decene, homopolymer, hydrogenated) was administered to 30 Sprague-Dawley Crl:CD®BR VAF/Plus® rats/sex/dose by gavage at dose levels of 0, 100, 500, or 1000 mg/kg bw/day (Daniel, 1994). Both males and females were treated for 4 weeks prior to mating and through mating. At the end of mating, males were sacrificed. Females were treated through gestation and until lactation day 21.

 

There were no treatment-related effects on clinical signs, mortality, body weight, or gross pathology in the parental generation or in the pups through lactation day 21. There were no treatment related effects on reproduction or pup viability. Some pups were used further in a subchronic study with the remainder sacrificed on lactation day 21. There is no parental or offspring systemic or reproduction LOAEL, based n the lack of effects. The parental systemic and reproduction NOAEL is 1000mg/kg bw/day in males and females. The offspring NOAEL is 1000 mg/kg bw/day even after the additional 91 day subchronic exposure.

In a one-generation reproduction study, Alkane 4 was administered orally, once daily, by gavage to three groups each of twenty-four male and twenty-four female Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, at dose levels of 1000, 250 and 50 mg/kg/day (Knox et al., 2007; Klimisch score=1). A further group of twenty-four male and twenty-four female rats received the vehicle alone to serve as a control.

 

There were two unscheduled deaths on the study, occurring in the control and 250 mg/kg/day dosage groups, neither of which was associated with treatment. There were no signs of clinical toxicity observed in either sex at any of the doses tested. Behavioural and functional performance remained unaffected in male and female rats treated with Alkane 4. Sensory reactivity, body weight, food and water consumption were unaffected as were fertility and mating performance.Haematological and clinical chemistry assessments revealed no significant treatment-related effects on male and female rats.

 

No treatment-related effects on offspring growth or development were detected. Litter sizes from birth to weaning were essentially similar across all dose groups. Gross necroscopy did not reveal any remarkable findings and neither did histopathology.

 

The oral administration of Alkane 4 to rats by gavage at a maximum dose level of1000 mg/kg/day, throughout maturation, mating, gestation and lactation resulted in no treatment related effects. Thus, the NOAEL for adult toxicity and reproductive and developmental toxicity was considered to be 1000 mg/kg/day.

No adverse fertility effects were reported in either study; therefore the NOAEL was 1000 mg/kg bw/day for both studies (highest dose tested). While these studies were well-conducted and scientifically sound, DNELS for this endpoint were not derived.  This is because even though the weight of evidence from these two studies suggests that Category E substances do not present a significant hazard potential to fertility and development, these studies cannot be substituted for a full two-generation study (OECD 416). Further testing has been proposed for these endpoints and although a DNEL for fertility can be derived from the one-generation study with Alkane 4, formal development of worker and general population DNELs for these endpoints will be deferred until results from the two generation study are available.

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for poly alpha olefins using Alkane 4 as an analogue. Alkane 4, like other compounds in this category, is a poly alpha olefin, i. e., highly branched isoparaffinic chemicals produced by oligomerization of oct-1 -ene, dec-1 -ene, and/or dodec-1-ene. Therefore its physiochemical and toxicological properties are expected to be similar to those of other poly alpha olefins.


Short description of key information:
Two read-across studies were identified for poly alpha olefins and their structural analogues: a 91-day study which assessed the systemic toxicological effects of treatment with 1 -decene, homopolymer, hydrogenated (Ethylflo 166) on rats previously treated in utero with the same chemical and a 90-day study with Alkane 4 which assessed fertility and developmental effects in a one-generation study (OECD 415). Neither study showed any treatment-related effects on fertility or reproductive endpoints in rats. Both studies repored a NOAEL of 1000 mg/kg bw.

Effects on developmental toxicity

Description of key information
Not expected to cause developmental toxicity.

Justification for classification or non-classification

No developmental or 2-generation reproductive toxicity data were available for 1 -decene trimer, hydrogenated and tetramers. Two one-generation reproduction toxicity studies from 1 -decene, homopolymer, hydrogenated and structural analogues related to 1 -decene trimer, hydrogenated and tetramers (i. e., Alkane 4) showed no effects on reproductive parameters. Although results from these studies showed no reproductive or developmental effects at the highest dose tested, and while the data in combination present a reasonable weight of evidence upon which to judge the reproductive and developmental toxicity of the Category, these study results cannot meet the requirement for results from a complete developmental or two-generation reproductive study. Nonetheless, the results do not raise concern with regard to classification of 1 -decene trimer, hydrogenated and tetramers as toxic for reproduction or development toxicants under EU Dangerous Substances Directive 67/548/ECC or CLP EU Regulation 1272/2008 (GHS aligned).