Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
125 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
High quality study but it is read across, awaiting final decision on testing proposal for a two generation reproduction study on 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There is no specific test data on potential reproductive toxic effect of the read across substance 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9. The available information is on a related substance Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9, this substance is predominantly C12 but does contain >10% C18 while 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 is predominantly C18. The available study is an OECD 422 reproductive screening test. There were some indications of foetotoxicity in this study (post implantation loss) but this was considered not sufficient for classification, it was proposed to do additional testing to establish if there is developmental toxicity caused by the test substance . There were no indications of any effects on reproductive performance or fertility. The lack of potential for this is also supported by the lack of any adverse effects on the reproductive organs in the OECD408 90 day dosing study in rats on 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9. There were no effects on the weight of the reproductive organs or seen when examined histopathologically. Also in addition the females were examined for any abnormality in the oestrus cycle and the males for abnormality in the spermatogenic cycle. No abnormalities were seen which supports the lack of potential for reproductive toxicity in the adult rats.

The read across to Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9 is not ideal due to the difference in carbon chain length distribution. As 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 is a high volume substance >1000 tonnes we have proposed to do both a pre-natal developmental toxicity OECD 414 study (now completed) and a two generation reproduction study (delayed due to a disagreement between ECHA and some member states). The potential for reproductive toxicity in particular developmental toxicity (post implantation loss) with this substance will then be assessed based on the results of these studies which will be reviewed to see if any classification is required. 

Short description of key information:

There is no specific test data on potential reproductive toxic effect of 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9.  Therefore a test proposal has been made for a two generation reproduction study this is delayed awaiting a final decision from ECHA and the member states. The only available information is on a related substance Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9, this substance is predominantly C12 but does contain >10% C18 while 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9  is predominantly C18.  The available study is an OECD 422 reproductive screening test.  There were no indications of adverse effects reproduction in the parental animals. There were some indications of foetotoxicity in this study but this was considered not sufficient for classification, it is proposed to do additional testing to establish if there is developmental toxicity (post implantation loss) also caused by 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9.

Justification for selection of Effect on fertility via oral route:

A two generation reproduction study has been proposed for this substance, until this is completed there is no specific test data on the potential adverse effects of 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 on fertility or other reproductive parameters.  The only available information is on a related substance Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9, this substance is predominantly C12 but does contain >10% C18 while 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9  is predominantly C18.  The available study is an Klimisch 1, full GLP, OECD 422 reproductive screening test due to the shorter carbon chain length it is considered a worst case read across.

Justification for selection of Effect on fertility via inhalation route:

The low vapour pressure of the substance means inhalation is not considered to be relevant route of exposure so not testing is required.

Justification for selection of Effect on fertility via dermal route:

The corrosive properties of this substance mean the repeated dose dermal studies are not scientifically justified due to concerns for animal welfare.

Effects on developmental toxicity

Description of key information

There is an OECD414 pre-natal developmental toxicity study on 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9. This study showed no indication of developmental toxicity in the foetuses, the NOEL being 150mg/kg.  There was however also no indication of toxicity in the pregnant females.  This study does not include dosing during the implantation period, the only available information concerning this is read across to the OECD422 study on Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9.  This substance is predominantly C12 but does contain >10% C18 while 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9  is predominantly C18.  The available study is an OECD 422 reproductive screening test.  There were some indications of foetotoxicity (increased post implantation loss)  in this study but this was considered not sufficient for classification, it has been proposed to do a reproduction study to establish if this is also seen with 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
This study is high quality and replaces the read across to Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9 for developmental toxicity but it does not cover the period immediately after implantation so it does not supersede the read across to the OECD422 study where increased post implantation loss was seen. This will be resolved when the proposed reproduction study on 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 is available.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The OECD414 pre-natal development study included dose levels of 15, 50 and 150mg/kg bodyweight of 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9, administered by gavage for days 5 to 19 of pregnancy as a solution in arachis oil. The dose levels were selected based on those used in the 28 day and 90 day repeat dose studies. The adult females did not show any signs of toxicity in this study such as on bodyweights, or food or water consumption, but there was no histopathological examination of their stomachs making it not possible to see local adverse (irritant/corrosive) effects due to the corrosive/irritant nature of the test material as seen in the other repeat dose studies.

The absence of toxic effects in the adult females is not considered to be of concern as we have good evidence from the 28 day repeat dose study that higher doses could result in mortality or severe toxicity due to local effects in the stomach. 

The number of implantations, subsequent embryofoetal survival and litter size, sex ratio

and mean foetal, litter and placental weights on Day 20 of gestation were unaffected by maternal treatment at 15, 50 or 150 mg/kg bw/day.

 

There was no effect of maternal treatment on morphological development of the foetuses at 15, 50 or 150 mg/kg bw/day.

 

Conclusion

 

The No Observed Effect Level (NOEL) for the pregnant females and the survival, growth and embryofoetal development of the offspring was considered to be 150 mg/kg bw/day.2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9, did not show any indications of potential for developmental toxicity in this study. The proposed reproduction study will allow an assessment if the increased post implantation loss seen with the read across substance 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9 is also seen with this substance.

 

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

We have a Klimisch 1 full GLP compliant OECD414 study on 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9.

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

The low vapour pressure of the substance means inhalation is not considered to be relevant route of exposure so not testing is required.

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

The corrosive properties of this substance mean the repeated dose dermal studies are not scientifically justified due to concerns for animal welfare.

Justification for classification or non-classification

There is no specific test data on potential reproductive toxic effect of 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9. The available information is on a related substance Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9, this substance is predominantly C12 but does contain >10% C18 while 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 is predominantly C18. The available study is an OECD 422 reproductive screening test. There were some indications of foetotoxicity (increased post implantation loss) in this study but this was considered not sufficient for classification, it was proposed to do additional testing to establish if there is true developmental toxicity. There were no indications of any adverse effects on the reproductive parameters such as fertility in the adult rats of either sex. The lack of potential for this is also supported by the lack of any adverse effects on the reproductive organs in the OECD408 90 day dosing study in rats on 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9. There were no effects on the weight of the organs or when examined histopathologically. Also in addition the females were examined for any abnormality in the oestrus cycle and the males for abnormality in the spermatogenic cycle. No abnormalities were seen which supports the lack of potential for reproductive toxicity.

The read across to Ethanol, 2, 2’-iminobis-, N-coco alkyl derivs CAS No 61791-31-9 is not ideal due to the difference in carbon chain length distribution. As 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 is a high volume substance >1000 tonnes we have proposed to do both a developmental toxicity OECD 414 study (which is now completed) and a two generation reproduction study which is currently awaiting a final decision due to differences of opinion between some member states and ECHA on the replacement of the two generation study with an Extended one generation study.

 

The OECD414 pre-natal development study in rats, showed no evidence of developmental toxicity even at the top dose of 150mg/kg bodyweight therefore while this study does not include dosing during the pre-mating period until day 4, it does not indicate any potential for developmental toxicity. Until the reproduction study is available it is not possible to know if the increased post implantation loss see in the OECD422 study with the read across substance Ethanol, 2,2’-iminobis-,N-coco alkyl derivs CAS No 61791-31-9 will also be seen with this substance. However the evidence from the OECD414 study indicates that 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 does not induce developmental toxicity in rats, therefore it is clear that it is not necessary to classify this substance for reproductive or developmental toxicity based on the current data. A final conclusion concerning the post implantation loss and its relevance to this substance will be possible when the reproduction study is completed.