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Description of key information

RA-S CAS 112-84-5, Subacute oral (4 weeks), rat: NOAEL = 10000 mg/kg bw/d (converted from 100000 ppm in feed)
RA-S CAS 112-84-5, 90 day Repeated Dose Toxicity: oral proposed for CAS 112-84-5, which will be used for read-across
Data waiving - Repeated dose toxicity: inhalation
Data waiving - Repeated dose toxicity: dermal

Key value for chemical safety assessment

Additional information

There is no data on repeated dose toxicity available for Amides, C16-C18 (even numbered).

The only available data which can be used for a first assessment of repeated dose toxicity of fatty acid amides is a subacute 4-week feeding study with the structurally-related substance erucamide (CAS 112-84-5) in weanling rats (Wisconsin Alumni Research Foundation, 1960) which was well-conducted considering the time of realisation. In this study 5 male weanling rats of 45-50 g of body weight were fed with a diet containing an extremely high concentration of 100000 ppm (10 % w/w) of erucamide at the expense of sucrose which were compared to a control group fed on a diet without added fat. Individual body weight and food consumption data were collected weekly; the total output of feces was collected daily, and pooled weekly fecal samples were weighed and analysed for their fat content. At the end of the 4-week feeding period the animals were subjected to routine hematology and urinalysis, then the animals were sacrificed and a gross pathological examination was performed. Additionally histopathological samples were prepared for possible subsequent examinations.

No mortality occurred during the course of the study, and no clinical signs of toxicity were observed. The treated animals showed slightly lower body weight gain than the control, but their food consumption was lowered, as well, while food efficiency was comparable. However, due to the high substance concentration in the food the reduced food consumption could well be a sign of food denial because of palatability problems which is commonly observed in feeding studies with high substance concentrations. Reduced body weight gain then has to be considered as a secondary effect due reduced food consumption, but not as sign of systemic toxicity. Weekly numbers of 72.9, 57.3, 68.6 and 52.8% test substance absorption for the first, second, third and fourth week, respectively, were obtained. No effects were observed in hematology and urinalysis parameters, and the animals did not show any gross pathological abnormalities. Therefore, a concentration of 100000 ppm of erucamide in feed, which can be converted to a dose of 10000 mg/kg bw/day, was considered as NOAEL. Conversion was done based on the recommendations by the Toxicologist's Pocket Handbook (CRC Press, 2000). The applied conversion factor considers the typical amount of food uptake of animals at that respective age and weight. Although only 4 weeks in duration this study already impressively demonstrates that the tested substance does not exert any systemic toxicity effects due to the extremely high concentration chosen for dosing. Even if the resulting NOAEL is corrected for duration by use of an assessment factor of 3, as suggested by the "ECHA Guidance on information requirements and chemical safety assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health" for the conversion of subacute NOAELs to subchronic ones, the resulting corrected NOAEL of 3333 mg/kg bw/d will still be more than 30-fold higher than the subchronic dose level resulting in a classification for STOT-Repeated Exposure.

Due to the fact that the duration of the study is not sufficient to cover the demands of a substance registration with more than 1000 tonnes/year, a 90-day subchronic repeated dose toxicity study according to OECD Guideline 408 is proposed by the Lead Registrant of the structurally related substance erucamide (CAS 112-84-5), who is also a member of the Fatty Amides Consortium. Those results will be shared and used for a read-across to satisfy the data requirements for repeated dose toxicity of Amides, C16-C18 (even numbered), as well. The utilisation of such surrogate data from a structurally related substance for regulatory purposes is reasonable and justified according to Regulation (EC) No 1907/2006, Annex XI, article 1.5, especially in the light of animal welfare and considering the physical chemical and toxicokinetic similarities of Amides, C16-C18 (even numbered) and erucamide. Therefore, no individual repeated dose toxicity study with Amides, C16-C18 (even numbered) is proposed.

Justification for classification or non-classification

Based on the results for the structurally related substance erucamide, and according to the criteria of Directive EU 67/548/EEC and the criteria of Regulation (EC) No 1272/2008, the substance does not have to be classified for specific target organ systemic toxicity after repeated exposure.