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Administrative data

Description of key information

Based on read-across following a category approach: 
Oral: LD50 (rat) > 5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
5 000 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

There are no data available on the acute toxicity of fatty acids, C18-unsaturated, trimers upon oral, dermal or inhalative exposure. Therefore, assessment of acute toxicity was based on read-across from a group of structurally related substances within a category approach.

Oral

The acute oral toxicity of fatty acids, C18-unsaturated, dimers (CAS No. 61788-89-4) 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 5000 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 combined LD50 value for males and females was estimated to exceed 5000 mg/kg bw (Thouin, 1986).

In an earlier non-GLP study similar to OECD Guideline 401, the LD50 value for male and female Wistar rats given fatty acids, C18-unsaturated, dimers by gavage was determined to be greater than 18600 mg/kg bw. Transient sluggishness and slight diarrhoea were reported as clinical signs, which had diappeared at 24 h post-treatment (Spanjers, 1982).

The acute oral toxicity of fatty acids, C18-unsaturated, dimers, hydrogenated (CAS No. 68783-41-5) was tested in a study compliant with EU Method B.1 (Acute toxicity (oral)) under GLP conditions. The test material was administered by gavage to 5 male and 5 female Wistar rats at 5000 mg/kg bw. No mortalities and no signs of toxicity were observed during and at the end of the study (day 14 post-administration). Under the conditions used in this study, it was concluded that the test substance has no toxic effect when administered to the rat at a level of 5000 mg/kg bw. Thus, the LD50 value for males and females was estimated to be greater than 5000 mg/kg bw (Reijnders, 1988).

In another GLP-study conducted according to OECD Guideline 401, fatty acids, C18-unsaturated, dimers, hydrogenated were 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).

In an earlier non-GLP study similar to OECD Guideline 401, the LD50 value for male and female Wistar rats given fatty acids, C18-unsaturated, dimers, hydrogenated by gavage was determined to be greater than 18800 mg/kg bw. Transient sluggishness and slight diarrhoea were reported as clinical signs, which had diappeared at 24 h post-treatment (Spanjers and Til, 1982).

In addition, information on toxicokinetics of di- and oligomerised fatty acids formed during heating of vegetable oils indicate that absorption via the gastrointestinal tract is inversly proportional to chain length and grade of polymerisation (see Toxicokinetics). Thus, absorption and bioavailabilty of fatty acid trimers is unlikely to be higher than that of fatty acid dimers.

In conclusion and based on read-across from structurally related substances as well as toxicokinetic data on heated vegetable oils, fatty acids, C18-unsaturated, trimers are not expected to induce systemic toxic effects after ingestion.

 

Dermal

No information is available on systemic toxicity after acute dermal exposure to fatty acids, C18-unsaturated, trimers or other members of the chemical category they belong to.

Based on the physicochemical properties (lipophilic substance with low water solubility) fatty acids, C18-unsaturated, trimers are expected to readily penetrate the stratum corneum, but partition into the epidermis, and thus dermal uptake, is likely to be low. Due to variations in the grade of saturation and type of trimeric structure, the molecular weight of fatty acids, C18-unsaturated, trimers is not restricted to a single value. However, the overall molecular weight of a C54 chain is calculated to be clearly above 500 g/mol, hence too large for being dermally absorbed. Furthermore, taking into account the results of acute oral toxicity as well as skin and eye irritation studies conducted with other category members, no systemic toxic effects are expected after acute dermal exposure.

 

Inhalation

There are no data available on the acute toxicity upon inhalation exposure for fatty acids, C18-unsaturated, trimers or further members of the chemical category they belong 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

Based on read-across following a category approach, the available data on the acute toxicity of fatty acids, C18 -unsaturated, trimers is conclusive but not sufficient for classification.