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Description of key information

Reliable studies on oral repeated dose toxicity are available for the following category members:
Subchronic: NOAEL oral = ca. 5000 mg/kg bw/d; CAS# 143-07-7, C12 (Fitzhugh 1960)
Subchronic: NOAEL oral = 1000 mg/kg bw/d; CAS# 112-85-6, C22 (Nagao 2002)
No data are available for repeated dose toxicity after dermal exposure and inhalation, respectively.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Mode of Action Analysis / Human Relevance Framework

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 toxicity potential of fatty acids after repeated exposure is expected as it could be demonstrated with C16 fatty acid (lauric acid) and with C22 fatty acid (docosanoic acid), respectively.

The repeated dose toxicity of docosanoic acid was evaluated in a combined repeated dose and reproductive/developmental toxicity screening test performed under GLP according to OECD guideline 422 (Nagao et al, 2002). Groups of 13 male and 13 female Sprague-Dawley rats per dose 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 from 14 days prior to mating until day 3 of lactation. As a result of this treatment, neither mortality nor abnormalities in general condition were observed. In addition, no changes in body weight, body weight gain and food consumption were found in all dose groups. The observed minor changes in the corpuscular hemoglobin concentration, glucose, chloride, calcium and alkaline phosphate levels were regarded as incidental which also holds true for the observed changes in liver weights in male and kidney weights in females, respectively. All histological findings noted in all dose groups were also detected in the control groups, so that all findings could be regarded as not treatment-related. Overall, no treatment-related adverse effects were apparent, so that the highest administered dose of 1000 mg/kg bw/d is regarded as the NOAEL for docosanoic acid under the experimental conditions of this study.

Repeated dose toxicity of lauric acid was analyzed in a study, where 5 male Osborne-Mendel rats were fed a diet containing 10% lauric acid for 18 weeks (Fitzhugh et al., 1960). As results, no clinical effects, no adverse effects on weight gain nor any mortality was noted. The performed gross organ pathology and did not reveal any significant differences of individual organ weights between the controls and test animals. Thus, the given dosage of 10% lauric acid in the diet is regarded as the NOAEL, which corresponds to ca. 5000 mg/kg bw/d, based on an average daily food consumption of 5 g/100 g bw.

In a third study which is insufficient for assessment due to limited documentation, palmitic acid was adminstered to rats in the diet for six weeks at a dose of 4600 mg/kg bw/d. According to the authors, palmitic acid caused the hyperlipidemia (i.e. an excess of fats or lipids in the blood). No further information was provided.

Taken together, the study data do not provide any evidence of toxicity after repeated administration 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 repeated dose toxicity, fatty acids do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.