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Key value for chemical safety assessment

Effects on fertility

Description of key information

Short description of key information:


Two read-across studies were identified for poly alpha olefins and its 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 reported a NOAEL of 1000 mg/kg bw.

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
Additional information

Two read-across studies were identified for poly alpha olefins and their structural analogue, Alkane 4: 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). 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). 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 a one-generation study with Alkane 4; a structural analogue of dec-1-ene, dimers, hydrogenated, at the limit dose of 1000 mg/kg/day (Knox et al., 2007).  No treatment-related effects were reported in rats treated in utero and then subsequently treated an additional 91 days after birth with Ethylflo 166 (1-decene homopolymer, hydrogenated, Daniel, 1994).  The NOAEL was 1000 mg/kg/day for both studies (highest dose tested). The weight of evidence presented by these studies suggests that poly alpha olefins, as a group, are unlikely to present a significant hazard potential to fertility; therefore a DNEL for this endpoint is not necessary.

 

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.


Effects on developmental toxicity

Description of key information
 Testing proposal for Prenatal Developmental Toxicity Study according to OECD 414, first species (rat) is included.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available (further information necessary)

Justification for classification or non-classification

No developmental or 2-generation reproductive toxicity data are available for dec-1-ene, dimers. Information is available from two OECD 415 one-generation reproduction toxicity studies from 1-decene, homopolymer, hydrogenated and structural analogues related to dec-1 -ene, dimers, hydrogenated (i. e., Alkane 4) and showed no adverse effects on the general condition and reproductive performance of the parental animals or the growth and viability of their offspring at the highest dose tested.

The reproductive toxicity results are considered adequate and do not raise concern with regard to classification of dec-1-ene, dimers, both hydrogenated and unhydrogenated as toxic for reproduction under CLP EU Regulation 1272/2008 (GHS aligned).

Since the design of the OECD 415 study does not provide complete information on the potential effects of a substance on all aspects of foetal development, REACH Annex IX stipulates that pre-natal developmental toxicity study (following method B.31 of the Commission Regulation on test methods as specified in REACH Article 13(3), equivalent to OECD Test Guideline 414) be conducted in first species (rat) using a route of administration appropriate for the likely route of human exposure.