Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No other concerns identified.
Additional information

Screening data selected from linear alpha olefins consist of one reproductive/developmental toxicity screening test and one combined repeated dose/ reproductive/developmental toxicity screening test. Sperm counts were measured in a 90 -day inhalation study for hex-1 -ene. Results for this study are presented in the Repeated Dose Toxicity section of the CSR. Key studies selected from linear alpha olefins are summarized below. 

 

In a read-across screening for reproductive/developmental toxicity study from hex-1-ene, hex-1-ene was administered via gavage to twelve Sprague-Dawley rats/sex/dose at doses of 0, 100, 500, or 1000 mg/kg/day (Daniel, 1995b). The test material was composed of equal amounts of Neodene 6 alpha olefin, hexene-1 Gulftene 6, and alpha olefin C6 hex-1 -ene, which were obtained from different sources. Males were treated for 44 days beginning 28 days prior to mating and females were treated for 41 to 55 days beginning 14 days prior to mating through lactation day 4.

 

No reproductive effects were observed. There was a slight, but significant, decrease in absolute epididymal weight at all concentrations. The relative epididymal to brain weight was only significantly decreased in the low-dose group. Although the absolute epididymides weight was significantly decreased in parental males; the change was within 10% of the control, there was no dose response, there was no effects noted microscopically, and there were no effects on fertility. Therefore, this was not considered to be toxicologically significant. The NOAEL for reproductive toxicity was 1000 mg/kg/day.

 

In a read-across reproductive/developmental toxicity screening study from tetradec-1-ene (Daniel, 1995a), tetradec-1-ene was administered via gavage to twelve Sprague-Dawley Crl:CDBR VAF/Plus rats/sex/dose at doses of 0, 100, 500, or 1000 mg/kg/day (5 mL/kg of 0, 20, 100, or 200 mg/mL solution in corn oil). The test material was composed of equal amounts of Neodene 14 alpha olefin, alpha olefin C14 tetradec-1-ene, and tetradec-1ene Gulftene 14, which were obtained from different sources. Males were treated for 43 to 47 days beginning 28 days prior to mating and females were treated for 42 to 51 days beginning 14 days prior to mating through lactation day 4.

 

No reproductive effects were observed. There were clinical signs noted in 500 and 1000 mg/kg/day females, but they were unrelated to reproduction. There was no LOAEL for this study. The NOAEL for reproductive toxicity was 1000 mg/kg/day.

Sperm counts were examined in the 90 -day inhalation study on hex-1 -ene (Bennick et al., 1984). In this study, hex-1-ene was administered to forty Fischer 344 rats/sex/concentration by dynamic whole body exposure at concentrations of 0, 300, 2000, or 3000 parts per million (equivalent to 0; 1033; 3442; and 10,326 mg/m3, respectively) for 6 hours a day, 5 days a week, for 13 weeks. According to the report, there were no effects on sperm count after exposure.

 

No adverse fertility effects were reported in either screening study (OECD 421 and/or OECD 422); therefore the NOAEL was 1000 mg/kg bw/day for both studies (highest dose tested). The weight of evidence presented by these studies suggests that linear alpha olefin substances, as a group, are unlikely to present a significant hazard potential to fertility; therefore a DNEL for this endpoint is not necessary.  However, although reassuring, such information does not fully meet the REACH information requirement for this endpoint; therefore a two-generation study (OECD 416) is proposed in the registration dossier.  Results from this study, when available, will be reviewed, and if justified, a DNEL will be proposed at that time.


Short description of key information:
Read across screening reproductive/developmental studies were identified from hex-1-ene (OECD 421) and from tetradec-1-ene (OECD 422). No reproductive effects were observed in either study.

In addition, sperm counts were examined in the 90-day inhalation study (OECD 413) on hex-1-ene. According to the report, there were no effects on sperm count.

Effects on developmental toxicity

Description of key information
Read across screening reproductive/developmental studies were identified from hex-1-ene (OECD 421) and from tetradec-1-ene (OECD 422).  No developmental effects were observed in either study. 
Additional information

Screening data selected from linear alpha olefins consist of one reproductive/developmental toxicity screening test and one combined repeated dose/ reproductive/developmental toxicity screening test. Key studies selected from linear alpha olefins are summarized below. 

 

In a screening for reproductive/developmental toxicity study from hex-1-ene, hex-1-ene was administered via gavage to twelve Sprague-Dawley rats/sex/dose at doses of 0, 100, 500, or 1000 mg/kg/day (Daniel, 1995b). The test material was composed of equal amounts of Neodene 6 alpha olefin, hexene-1 Gulftene 6, and alpha olefin C6 hex-1 -ene, which were obtained from different sources. Males were treated for 44 days beginning 28 days prior to mating and females were treated for 41 to 55 days beginning 14 days prior to mating through lactation day 4.

 

No developmental effects were observed. Therefore, the NOAEL for developmental toxicity was 1000 mg/kg/day.

 

In a read-across reproductive/developmental toxicity screening study from tetradec-1-ene (Daniel, 1995a), tetradec-1-ene was administered via gavage to twelve Sprague-Dawley Crl:CDBR VAF/Plus rats/sex/dose at doses of 0, 100, 500, or 1000 mg/kg/day (5 mL/kg of 0, 20, 100, or 200 mg/mL solution in corn oil). The test material was composed of equal amounts of Neodene 14 alpha olefin, alpha olefin C14 tetradec-1-ene, and tetradec-1ene Gulftene 14, which were obtained from different sources. Males were treated for 43 to 47 days beginning 28 days prior to mating and females were treated for 42 to 51 days beginning 14 days prior to mating through lactation day 4.

 

No developmental effects were observed. There were clinical signs noted in 500 and 1000 mg/kg/day females, but they were unrelated to development. There was no LOAEL for this study. The NOAEL for developmental toxicity was 1000 mg/kg/day.

No adverse developmental effects were reported in either screening study (OECD 421 and/or OECD 422); therefore the NOAEL was 1000 mg/kg bw/day for both studies (highest dose tested).  The weight of evidence presented by these studies suggests that linear olefin substances, as a group, are unlikely to present a significant hazard potential to foetal development; therefore a DNEL for this endpoint is not necessary.  However, although reassuring, such information does not fully meet the REACH information requirement for this endpoint; therefore a developmental study (OECD 414) is proposed in the registration dossier.  Results from this study, when available, will be reviewed, and if justified, a DNEL will be proposed at that time.

Justification for classification or non-classification

No developmental or 2-generation reproductive toxicity data are available for icos-1-ene. Two screening reproductive/developmental toxicity studies from hex-1-ene and tetradec-1 -ene showed no effects on reproductive parameters. Although results from the developmental/reproductive screening study for hex-1-ene and tetradec-1-ene 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 linear alpha olefins, 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 icos-1-ene as toxic for reproduction under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 (GHS aligned).