Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

- subacute toxicity / reproduction screening, rat, OECD 422 (BASF SE, 2013, 85R0674/12X380): NOAEL reproduction (fertility) toxicity: 150 mg/kg bw/day (reduced testis and epididymis weights) LOAEL reproduction (developmental) toxicity: 50 mg/kg bw/day (higher mean incidence of post-implantation loss) LOAEL systemic: 50 mg/kg bw/day (Specific target organ toxicity: heart (cardiomyopathy) for read across substance Amines, triC8-10-alkyl

Additional information

There is no data available for tridodecylamine. A suitable read across candidate for which data is available isAmines, tri-C8 -10 -alkyl (CAS # 68814 -95 -9):

A study investigating the toxicological effects of the test item Amines, tri-C8-10-alkyl to rats according to OECD guideline 422 resulting from repeated oral-gavage administration is performed. Amines, tri-C8-10-alkyl was administered in corn oil as vehicle at dosages of 50, 150 and 400 mg/kg body weight/day, and controls received the vehicle only. Amines, tri-C8-10-alkyl was administered to male rats for 43 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. All animals survived until scheduled necropsy. There were no test item related clinical signs in both genders at 50 mg/kg bw/day. At 150 mg/kg bw/day, no signs of discomfort were observed; food consumption and body weights were similar to controls. A reduction in food consumption and body weight was noted in males and females at 400 mg/kg bw/day when compared with controls. Furthermore, higher values of aspartate aminotransferase, alanine aminotransferase and of alkaline phosphatase were noted in both genders at 400 mg/kg bw/day, without a histopathological correlate in the liver. Mean precoital time, fertility index and conception rate were not affected by the treatment with the test item at any dose level. At a dose level of 150 and 400 mg/kg bw/day, no female gave birth. In both dose groups, a post implantation loss of 100% was noted, since all pregnant females had either only implantation sites or only embryonic resorptions. At 50 mg/kg bw/day, a higher mean incidence of post-implantation loss was noted. In males, reduced testes and epididymides weights were noted at a dose level at 400 mg/kg bw/day. In all treatment groups (50, 150 and 400 mg/kg bw/day), cardiomyopathy was noted in the heart, and foamy macrophages accumulation was observed in the lungs. The mean number of pups at first litter check was not affected by the treatment with the test item. The sex ratio was also not affected. No abnormal pup was noted at any dose level. No effects on pup weight and pup weight gain were observed. At necropsy of pups, there were no abnormal findings. Key study assignment: As there is only one reliable and relevant study investigating the reproductive toxicity of Amines, tri-C8-10-alkyl.this study is integrated as key study. Assessment of toxicity on reproduction: Based on these results, no NOAEL (No Observed Adverse Effect Level) could be established for general toxicity and reproduction in this study. Nevertheless, a dose response correlation could be observed showing that, for example, the post implantation losses decrease lowering the dosage. Unfortunatley no lower dose than 50mg/kg bw/d was tested but using the trend observed in effects an extrapolation may be suitable. Therefore the applicant corrected the LOAEL for systemic toxicity of 50 mg/kg bw/d, based on cardiomyopathy in males, by an additional safety factor of 10 to receive a NOAEL. The same is assumed for the effects above. The risk assessment and classification will be based on the assumed NOAEL of 5 mg/kg bw/d. The effects observed above are effects concerning the fertility/developmental. Based on these findings the substance will be classified for reproduction toxicity (fertility/developmental).

Effects on developmental toxicity

Description of key information

- subacute toxicity / reproduction screening, rat, OECD 422 (BASF SE, 2013, 85R0674/12X380): NOAEL reproduction (fertility) toxicity: 150 mg/kg bw/day (reduced testis and epididymis weights) LOAEL reproduction (developmental) toxicity: 50 mg/kg bw/day (higher mean incidence of post-implantation loss) LOAEL systemic: 50 mg/kg bw/day (Specific target organ toxicity: heart (cardiomyopathy) for read across substance Amines, triC8-10-alkyl

Additional information

There is no data available for tridodecylamine. A suitable read across candidate for which data is available isAmines, tri-C8 -10 -alkyl (CAS # 68814 -95 -9):

A study investigating the toxicological effects of the test item Amines, tri-C8-10-alkyl to rats according to OECD guideline 422 resulting from repeated oral-gavage administration is performed. Amines, tri-C8-10-alkyl was administered in corn oil as vehicle at dosages of 50, 150 and 400 mg/kg body weight/day, and controls received the vehicle only. Amines, tri-C8-10-alkyl was administered to male rats for 43 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. All animals survived until scheduled necropsy. There were no test item related clinical signs in both genders at 50 mg/kg bw/day. At 150 mg/kg bw/day, no signs of discomfort were observed; food consumption and body weights were similar to controls. A reduction in food consumption and body weight was noted in males and females at 400 mg/kg bw/day when compared with controls. Furthermore, higher values of aspartate aminotransferase, alanine aminotransferase and of alkaline phosphatase were noted in both genders at 400 mg/kg bw/day, without a histopathological correlate in the liver.Mean precoital time, fertility index and conception rate were not affected by the treatment with the test item at any dose level. At a dose level of 150 and 400 mg/kg bw/day, no female gave birth. In both dose groups, a post implantation loss of 100% was noted, since all pregnant females had either only implantation sites or only embryonic resorptions. At 50 mg/kg bw/day, a higher mean incidence of post-implantation loss was noted.In males, reduced testes and epididymides weights were noted at a dose level at 400 mg/kg bw/day.In all treatment groups (50, 150 and 400 mg/kg bw/day), cardiomyopathy was noted in the heart, and foamy macrophages accumulation was observed in the lungs. The mean number of pups at first litter check was not affected by the treatment with the test item. The sex ratio was also not affected. No abnormal pup was noted at any dose level. No effects on pup weight and pup weight gain were observed. At necropsy of pups, there were no abnormal findings.Key study assignment:As there is only one reliable and relevant study investigating the reproductive toxicity of Amines, tri-C8-10-alkyl.this study is integrated as key study.Assessment of toxicity on reproduction:Based on these results, no NOAEL (No Observed Adverse Effect Level) could be established for general toxicity and reproduction in this study. Nevertheless, a dose response correlation could be observed showing that, for example, the post implantation losses decrease lowering the dosage. Unfortunatley no lower dose than 50mg/kg bw/d was tested but using the trend observed in effects an extrapolation may be suitable. Therefore the applicant corrected the LOAEL for systemic toxicity of 50 mg/kg bw/d, based on cardiomyopathy in males, by an additional safety factor of 10 to receive a NOAEL. The same is assumed for the effects above. The risk assessment and classification will be based on the assumed NOAEL of 5 mg/kg bw/d. The effects observed above are effects concerning the fertility/developmental. Based on these findings the substance will be classified for reproduction toxicity (fertility/developmental).

Justification for classification or non-classification

Based on these results, a NOAEL for reproduction could be established at 150 mg/kg bw but no NOAEL could be established for developmental toxicity in this study. The LOAEL was 50mg/kg bw, which was the lowest concentration tested. It cannot be excluded, that the test substance will cause adverse effects in concentrations lower than 50mg/kg bw/day. Nevertheless as the a trend in dose response relation concerning postimplantattions loses could be observed (decrease in loses with decrease dosage) an additional saftey factor correcting the LOAEL to a NOAEL of 10 is assumed to be suitable. As the effects seen are effects on fertility and developmental (postimplantation losses, reduced testis and epididymes weighs) the substance is labeled for reproduction and developmental toxicity as follows:

 

GHS: Repr. Cat. 1B (FD), Reproductive toxicity, H360: May damage fertility or the unborn child,

DSD: Repr. Cat. 2, Reproductive toxicity, R60: May impair fertility; R61 May cause harm to the unborn child.