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Key value for chemical safety assessment

Effects on fertility

Additional information

Fatty acids are found in all living organisms fulfilling fundamental physiological functions within the body. Based on this role within the body, no potential of fatty acids for affecting reproduction is expected as it could be demonstrated with fatty acids C22.

A NOAEL of 1000 mg/kg bw/d for fertility was found in a combined repeated dose toxicity study with the reproduction / developmental toxicity screening test performed according to OECD Guideline 422 with C22 fatty acid (Nagao et al., 2002). Groups of 13 male and 13 female Sprague-Dawley rats received daily doses of 100, 300 and 1000 mg/kg bw/d of docosanoic acid by gavage. While the males were treated for 42 days, the females received the test substance form 14 days prior to mating until day 3 of lactation. As result, neither mortality nor abnormalities in general condition were observed in all dose groups. Since also no difference in number of corpora lutea, implantation rate, number of implantations and all other reproductive parameters was noted in all treated groups and in the control group, there were no indications of any adverse effects on reproduction.


Short description of key information:
Studies on reproductive toxicity by the oral route are available for the following category members:
CAS# 112-85-6, C22: NOAEL oral (fertility) = 1000 mg/kg bw/d; highest dose tested (Nagao 2002), OECD 422
No data are available for reproductive toxicity after dermal exposure and inhalation, respectively.

Effects on developmental toxicity

Description of key information
Studies on developmental toxicity/teratogenicity by the oral route are available for the following category members:
CAS# 124-07-2, C8: NOAEL oral (developmental toxicity/teratogenicity) = 2704 mg/kg bw/d (Scott 1994)
CAS# 57-10-3, C16: NOAEL oral (developmental toxicity/teratogenicity) = 1500 mg/kg bw/d (Narotzky 1994)
CAS# 112-85-6, C22: NOAEL oral (developmental toxicity/teratogenicity) = 1000 mg/kg bw/d; highest dose tested (Nagao 2002), OECD 422
CAS# 124-07-2, C8: NOAEL oral (developmental toxicity/teratogenicity) = 600 mg/kg bw/d (Nau and Loescher 1986) RL4
No data are available for developmental toxicity/teratogenicity after dermal exposure and inhalation, respectively.
Additional information

Fatty acids are found in all living organisms fulfilling fundamental physiological functions within the body. Based on this role within the body, no potential of fatty acids for affecting development is expected as it could be demonstrated with C8 fatty acid (octanoic acid), C16 fatty acid (palmitic acid) and C22 fatty acid (docosanoic acid), respectively.

Developmental toxicity by octanoic acid was evaluated in a published study, where 12 Sprague-Dawley rats received a single dosage of 18.75 mmol/kg bw by gavage on day 12 of gestation (Scott et al, 1994). As a result of the dosing, severe maternal toxicity was noted, but not further specified. The analysis of fetuses was performed on day 20 of gestation. In addition, the content of octanoic acid in fetuses and in maternal fluid was analyzed 0.25, 0.5, 1, 2, 4, 8, and 24 hours after dosing. According to the author, the observed maternal toxicity was the reason for the slight reduction in the fetal body weight when compared to control values. However, no significant differences to control values were found regarding number of living fetuses, number of implantation sites, number of resorptions and number of malformations, respectively. Thus, the NOAEL for developmental toxicity was found to be 18.75 mmol/kg bw (total dose) corresponding to 2704 mg/kg bw octanoic acid.

The effect of palmitic acid on development was analyzed in a screening study with a Chernoff/Kavlock assay (Narotsky et al., 1994). Groups of 16 Sprague-Dawley rats received a daily dosage of 1125 and 1500 mg/kg bw/d in corn oil on gestation days 6 - 15 via gavage. A maternal mortality rate of 21% and 44% was found where ,according to the authors, most of the deaths could have been attributed to intubation error. However, maternal toxicity like rale and dyspnea was noted. There was a decrease in the number of live pups on post-gestational day 6, while no teratogenic effect was observed. Based on these findings, the NOAEL for teratogenicity is 1500 mg/kg bw/d, whereas the NOAEL for maternal toxicity was found to be below 1125 mg/kg bw/d.

A NOAEL of 1000 mg/kg bw/d was found for docosanoic acid in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test performed according to OECD Guideline 422 with C22 fatty acid (Nagao et al., 2002). Groups of 13 male and 13 female Sprague-Dawley rats received daily doses of 100, 300 and 1000 mg/kg bw/d of docosanoic acid by gavage. While the males were treated for 42 consecutive days, the females received the test substance form 14 days prior to mating until day 3 of lactation. Since the viability, the body weights, and the results of pathological examination of the pups did not reveal any differences between the dose groups and the control groups, there was no indication for any adverse effects on development.

In another study which is insufficient for assessment due to limited documentation, octanoic acid was injected subcutaneously once to mice at a dose of 600 mg/kg bw/d on day 8 of gestation (Nau and Loescher 1986). According to the authors, no significant differences compared to control were found for octanoic acid. No further information was provided.

Taking all the results together, the study data do not provide any evidence of developmental toxicity/teratogenicity of fatty acids which is supported by the physiological function of fatty acids within the body.

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for toxicity to reproduction/developmental toxicity/teratogenicity, fatty acids do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.