2-Butenedioic acid (E)-, di-C8-18-alkyl esters

Endpoint summary

Description of key information

LD50 (oral) > 2000 mg/kg bw, LD50 (dermal) > 5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

No data are available for the substance therefore data on a category substance -Didodecyl fumarate (CAS 2402-58-6)- are used for the assessment of acute toxicity. This substance was selected for testing, because it represents the category member with the shortest fatty alcohol side chain, and consequently with the lowest molecular weight, which is regarded as worst-case approach in terms of hazard assessment of the PFAE fumarates for the local as well as for systemic effects.

Acute toxicity - oral

In a GLP-compliant study according to OECD guideline 423, the acute oral toxicity of Didodecyl fumarate was studied in female Wistar rats (Höger, 2013). Two groups of three female rats consecutively received the test substance in corn oil at a dose of 2000 mg/kg bw and were observed for a period of 14 days. During the whole study, no mortalities were reported. In all animals of the first test group impaired general state and piloerection were observed at hour 1 and persisted in two animals until hour 4 or 5 after administration. Diarrhea was noted in one animal at hour 0 while cowering position was observed in all animals at hour 1. Clinical signs in the second test group revealed impaired general state and piloerection and were observed in one animal from hour 0 until hour 2 after administration. In two animals of this test group no clinical signs were observed during clinical examination. The mean body weight of the test groups increased throughout the study period within the normal range. There were no macroscopic pathological findings in any of the animals sacrificed at the end of the observation period.

Under the conditions of this study, the oral LD50 value of Didodecyl fumarate was greater than 2000 mg/kg bw.

Acute toxicity - inhalation

PFAE fumarates are pasty solids with calculated vapour pressures below 0.0001 Pa at 20 °C. Therefore, exposure via the inhalation route can be considered negligible under the identified use conditions.

Acute toxicity – dermal

The acute dermal toxicity of Didodecyl fumarate was tested in a GLP-conform study according to OECD guideline 402 (Höger, 2013). The clipped skin of dorsal and dorsolateral parts of 5 Wistar rats per sex was exposed to the test substance in corn oil at a limit dose of 5000 mg/kg bw for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No mortality and no clinical signs of toxicity were observed up to the end of the observation period. Overall body weight gains were not affected by treatment with the test substance in male and female animals. Necropsy and histopathological examination revealed no substance-related findings. Skin effects at the application site comprised very slight erythema (grade 1) in one out of five male and female animals at day 1. Animals were fully recovered by day 2.

Based on these results, the dermal LD50 value of Didodecyl fumarate was greater than 5000 mg/kg bw.

Conclusion for acute toxicity

One study is available studying the acute oral toxicity of PFAE fumarates category members resulting in oral LD50 values greater than 2000 mg/kg bw. As PFAE fumarates are pasty solids with calculated vapour pressures below 0.0001 Pa at 20 °C exposure via the inhalation route can be considered negligible under the identified use conditions and no further test is necessary. In the available acute dermal toxicity study with the same category member an LD50 value of 5000 mg/kg bw was determined.

Thus, the available data indicate a very low level of acute toxicity for the category members and thus no hazard for acute oral, inhalation and dermal toxicity was identified.

A detailed reference list and the justification for read-across are provided in section 13 of IUCLID and within CSR.

Justification for classification or non-classification

The available data on the category member show that it should not be classified according to the CLP Regulation (EC) No. 1272/2008. Since no available data are available for the substance, the data on the category member can be used for the (non) classification of the substance.

LD50 for both acute oral and acute dermal toxicity are greater than 2000 mg/kg bw. These values suggest that the substance should not be classified according to the CLP Regulation (EC) No. 1272/2008 for acute toxicity.