Registration Dossier

Administrative data

Description of key information

Acute toxicity:
- oral: LD50 > 5000 mg/kg bw
- dermal LD50 > 5000 mg/kg bw

Key value for chemical safety assessment

Additional information

Oral: Acute oral toxicity of octanoic acid was analyzed in a study performed under GLP according to OECD guideline 401. In this limit test 5 male and 5 female Wistar rats received a dose of 5000 mg/kg bw octanoic acid by gavage. No signs of systemic toxicity and no change in body weight gain were observed during the 14 day observation period. Macroscopic examination of animals at termination revealed only, firm and/or small white/greyish irregular patches in the forestomach of all animals. Since no mortality occurred, the LD50 was found to be >5000 mg/kg bw.
In another study conducted under GLP in accordance with OECD guideline 401, 5000 mg/kg bw for long chain fatty acid was administered by gavage to 5 male and 5 female Wistar rats (Kästner, 1981). After administration the animals showed salivation, reduced breathing and activity and reduced state, while in females also ataxia, lateral position, reduced corneal reflex were observed. However, all animals were free of symptoms from 24 hours on. Since no mortality occurred, the LD50 was found to be >5000 mg/kg bw.
Due to the structural and toxicological similarities of members within the category including 18 Di (871 -70 -5) the same result is has been determined.
Acute oral toxicity of CAS 871-70-5 octadecanedioic acid was evaluated in a test with rats performed similar to OECD Guideline 401. Ten animals received an oral application of 5000 mg/kg bw of the substance with corn oil. Two female animals have not survived with GI tract solid blockage; all other animals showed no clinical symptoms during the observation period and the no substance-related findings were observed at gross pathology. The survived animals showed also normal weight and gain during the study. Based on these results and considering the physical GI tract blockage, the LD50 was found to be > 5000 mg/kg bw.

 

Inhalation route is not relevant because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance - (annex VIII column 2 of REACH regulation) Data from the other two exposure routes (oral and dermal) are available.

 

Dermal:

A general prerequisite for systemic toxicity after dermal application is the permeability of the skin for the applied substance. Although the dermal penetration of fatty acids is very variable, in general they do not have significant systemic bioavailability (for details see IUCLID chapter 7.1).
Thus, no acute dermal toxicity by fatty acids is expected as it could be demonstrated by a LD50 value of >2000 mg/kg bw for C18 fatty acid (stearic acid) found in a in limit test performed according to internal company standards (Jones, 1979). Three male and three female New Zealand White rabbits received a dermal application of 2000 mg/kg bw stearic acid to 25% of the total body surface under occlusion for 24 hours. As result, slight diarrhoea was noted in one female animal on day 3 after treatment. All other animals appeared normal throughout the observation period. Laboured breathing on day 6 was noted in one male, which died the next day. Although the pathological examination revealed severe consolidation of the lungs, this finding was not considered to be substance related. Irritating effects were noted on the skin of all animals which were described as ranging from slight to severe. Four animals showed slight and moderate desquamation. Slight oedema and eschar formation were also noted in some animals during the first week of observation. However, these observed effects can be attributed to the severe conditions used for application which are not in line with current guidelines. However, a LD50 of >2000 mg/kg bw was found for stearic acid.
Although the dermal absorption of C18 fatty acid (stearic acid) with 0.00026 mg/cm2is lower compared to fatty acids with shorter chain lengths (e.g. C12 fatty acid: 0.005 mg/cm2), even single or repeated oral uptake of C12 fatty acid does not lead to systemic effects due to the physiological function within the body.
Moreover, dermal exposure can be considered to be sufficiently controlled in industrial and professional applications since the employees are wearing gloves and protective clothing. Thus, no acute dermal toxicity by fatty acids is expected and no further testing shall be performed due to animal welfare reasons.
The dermal LD 50 of the test substance CAS 871-70-5 octadecanedioic acid is >5000 mg/kg bw.

In conclusion, based on available data on various representative substances within the category, no acute dermal toxicity of fatty acids are expected.

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for acute toxicity, 1,18 octadecanedioic acid does not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.