Registration Dossier

Administrative data

Description of key information

OECD 423, oral rat: LD50cut-off 5000 mg/kg bw  (ATC method)
RA-S CAS 112-84-5, OECD 436, inhal. rat: LC50 >2.8 mg/L (ATC method), LC50cut-off ∞
RA-S CAS 112-84-5, OECD 402 dermal rat: LD50 >2000 mg/kg bw (limit test)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

There is data available from an acute oral toxicity study following OECD Guideline 423 (Acute Toxic Class Method) in form of a limit test with Amides, C16-C18 (even numbered) (Sanders, 2000). A starting dose of 2000 mg/kg bw was subsequently applied to 3 animals of each sex. No mortality occurred either in the females or in the males, no signs of systemic toxicity were observed, and the animals showed the expected gain in bodyweight during the study. Therefore, according to the scheme outlined in Annex 2d of OECD guideline 423 the LD50 cut-off value for acute oral toxicity was determined to be 5000 mg/kg bw.

No test data for Amides, C16-C18 (even numbered) is available for acute dermal and acute inhalation toxicity testing. Therefore, a read-across from a structurally related substance, erucamide (CAS 112-84-5), is included for regulatory purposes. Erucamide is the fatty acid amide resulting from the amidation of erucic acid. Erucic acid is a mono-unsaturated fatty acid with a carbon chain consisting of 22 carbon atoms with a double bond at position 13 (omega-9) of the carbon chain (cis-docos-13-enoic acid). Comparable to Amides, C16-C18 (even numbered) it is not classified in Annex I of Directive 67/548/EEC, and does not have to be self-classified according to the available experimental data. Erucic acid is also present in various oils and fats which are part of our diets (20-40% in oils from mustard seeds and up to 50% in original high erucic acid rapeseed oil, <2% in low erucic acid rapeseed oil; Beare-Rogers, 2001) and will also be broken down into shorter-chain fatty acids in the process of beta-oxidation. One of the most famoust uses is in Lorenzo's oil, a 4:1 mixture of the triglyceride forms of oleic and erucic acid, i.e. an investigational drug used for the treatment of adrenoleukodystrophy, for which an U.S. Patent was established. Testing of erucamide for acute oral toxicity following OECD guideline 423 as limit test with a starting dose of 2000 mg/kg bw, performed by the same testing facility as for Amides, C16-C18 (even numbered), revealed comparable results to Amides, C16-C18 (even numbered): no mortality occurred, no signs of systemic toxicity were observed, and animals showed the expected gains in bodyweight.

Therefore, both substances are considered to have comparable toxicological characteristics. Considering animal welfare reasons, a read-across from the tests for acute inhalation and dermal toxicity conducted with erucamide (CAS 112-84-5) is reasonable and justified.

The acute inhalation toxicity test was performed according to OECD Guideline 436 (Acute Toxic Class Method) with the maximum attainable aerosol concentration of erucamide still ensuring particles with a respirable MMAD as recommended in the guideline (Pothman, 2010). In the study the animals were nose-only exposed for 4 hours to an aerosol with MMADs ranging from 3.02 to 3.84 µm and a concentration of 2.8 mg/L. No mortality occurred, and the only effects observed during the 14-day observation period were ruffled fur one hour after the end of exposure and slight body weight loss from day 1 to day 2. No effects were observed from day 2 onwards. Therefore, the LC50 was established to be >2.8 mg/L for a 4-hour exposure period. According to OECD Guideline 436, Annex 5d for Acute Inhalation Toxicity testing with a starting concentration of 5 mg/L/4h for dusts and mists, the LC50 cut-off for acute inhalation toxicity can even be defined as "∞", as the starting dose already represented the maximum technically attainable concentration, and under handling conditions no higher concentration of a comparable respirable size will occur.

The acute dermal toxicity study with erucamide, designed as limit test, was performed according to OECD Guideline 402 (Braun, 2010). Five rats per sex were exposed for 24 hours to a dose of 2000 mg/kg bw under semicocclusive conditions. After exposure the treated skin sites were cleaned with lukewarm water and the dermal reactions were assessed. During the 14-day observation period no mortality occurred; no signs of systemic toxicity were observed, and the animals showed the expected gains of body weight. Local observations at the exposure site in form of slight desquamation were made in one male on observation days 7 and 8; no dermal effects were observed in the females. Therefore, the LD50 for acute dermal toxicity was determined to be >2000 mg/kg bw.

Justification for classification or non-classification

Based on the results for the test substance itself and the results obtained from the structurally related substance erucamide, Amides C16-C18 (even numbered) does not have to be classified for acute toxicity according to the EU Directive 67/548/EEC and the criteria of Regulation (EC) No 1272/2008.