Registration Dossier

Administrative data

Description of key information

Oral: LD50 (rat) > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for grouping of substances and read-across

In accordance with the specifications listed in Regulation (EC) No. 1907/2006 Annex XI, 1.5 Grouping of substances and read across, the similarity of category members has been shown to be justified based on the scope of variability and overlapping of composition, representative molecular structure, physico-chemical properties, tox-, ecotoxicological profiles and supporting Information by various validated QSAR methods. This information is given in further detail within the category justification for the grouping of chemicals and read-across (see IUCLID Section 13) for the dimerised fatty acids and its derivatives, and once more within the endpoint summary and discussion for Toxicokinetics.

For assessment of human health hazards of the category members, trends and similarities in toxicokinetic behaviour are most relevant. In particular, the molecular weight-dependent decrease in oral and dermal absorption and common metabolic pathways, which are explained by trends in molecular structure and common functional groups (monomers, dimers and trimers of similar long-chain fatty acids). This justifies the assumption that the toxicological profile of all category members is similar and effects or the lack of effects observed in toxicological studies of one ore more substances can also be expected and explained for the other substances in the category.

Therefore, in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, in order to avoid the need to test every substance for every endpoint, the category concept is applied for the assessment of human health hazards. Thus where applicable, human health effects are predicted from adequate and reliable data for reference substance(s) within the group by interpolation to other substances in the group (read-across approach).

All the available information from the substances within the category is taken into account for each endpoint to be assessed. Key studies are selected for assessment of the test substance and for read-across as to fulfil the requirements laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, i.e. in all cases the results are adequate for the purpose of classification and labelling and/or risk assessment; have adequate and reliable coverage of the key parameters addressed in the corresponding test method referred to in Article 13(3); cover an exposure duration comparable to or longer than the corresponding test method referred to in Article 13(3) if exposure duration is a relevant parameter; and adequate and reliable documentation of the applied method is provided.

 

Discussion

The acute toxicity of isooctadecanoic acid upon oral, dermal and inhalative exposure was assessed based on the available data for the substance.

Oral

The acute oral toxicity of isooctadecanoic acid was tested in a study compliant with OECD Guideline 401 and under GLP conditions. The test material was administered by gavage to 5 male and 5 female Wistar rats at 2000 mg/kg bw. No mortalities and no signs of toxicity were observed during and at the end of the study (day 14 post-administration). The LD50 value for males and females was estimated to exceed 2000 mg/kg bw (Reijnders, 1988).

In another GLP-study conducted according to OECD Guideline 401, isooctadecanoic acid was administered to 5 male and female Sprague-Dawley rats, respectively, by gastric force-feeding at a limit dose of 2000 mg/kg bw. There were no mortalities and no signs of toxicity after administration. Accordingly, the LD50 value was concluded to be greater than 2000 mg/kg bw (Saboureau, 1989).

Further studies conducted both under GLP and non-GLP conditions indicated that the LD50 value for male and female rats was greater than 5000 mg/kg bw, the animals showing transient signs of toxicity such as mucoid diarrhea, nasal hemorrhage and unkempt coats, all signs being reversible within the observation period (Nitka, 1988; Wallace, 1976).

Isooctadecanoic acid has been assessed for its safety as a cosmetic ingredient. In the safety assessment report, the acute oral toxicity of isooctadecanoic acid was evaluated on the basis of three studies on the undiluted test material and two studies on product formulations containing the test material at 2 and 4%, respectively. In each study, young albino rats were fasted overnight and given the test material in a single dose by gastric intubation. The undiluted test material was administered at doses ranging between 2 and 64 mL/kg bw as well as at 5000 and 15900 mg/kg bw. The 2 and 4% product formulations were given at 15900 and 15000 mg/kg bw, corresponding to 320 and 600 mg/kg bw of the test material, respectively. No mortalities occurred, except at 64 mL/kg (3 out of 5 rats died). Clinical signs included nasal hemorrhage (slight at 32 mL/kg, moderate to severe at 64 mL/kg), erratic locomotion prior to death and severe debilitation in the surviving animals at 64 mL/kg. From these data, the LD50 value was estimated to be between 32 and 64 mL/kg bw (CIR, 1983).

 

Dermal

There are no studies available on the acute dermal toxicity of isooctadecanoic acid or other members of the chemical category it belongs to.

Based on the physicochemical properties (lipophilic substance with low water solubility) isooctadecanoic acid is expected to readily penetrate the stratum corneum, but partition into the epidermis, and thus dermal uptake, is likely to be low. Furthermore, taking into account the results of acute oral toxicity as well as skin and eye irritation studies conducted with isooctadecanoic acid along with human exposure reports (CIR, 1983), no systemic toxic effects are expected after acute dermal exposure.

 

Inhalation

There are no data available on the acute toxicity upon inhalation exposure for isooctadecanoic acid or further members of the chemical category it belongs to. However, in view of the very low vapour pressure of all category members, human exposure via inhalation is unlikely.

Potential acute inhalation exposure to aerosols of formulations intended for spray applications is expected to be low under normal conditions of use (s. CSR Chapter 9).

Justification for classification or non-classification

The available data on the acute toxicity of isooctadecanoic acid is conclusive but not sufficient for classification.