Hexadecyl 2-ethylhexanoate

Endpoint summary

Description of key information

A 28 -day study (BASF, 1993) with the structural analogue Fatty acids, C8 -10, C12 -18 -alkyl esters is available, where no adverse effects were found revealing a NOAEL of 1000 mg/kg bw (highest dose tested).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable subacute toxicity study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

There are no data available for repeated dose toxicity of Hexadecyl 2-ethylhexanoate (CAS No. 59130-69-7). In order to fulfil the standard information requirements set out in Annex IX in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, 1.5, of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Repeated dose toxicity

CAS	59130-69-7	95912-86-0
Chemical name	Hexadecyl 2-ethylhexanoate	Fatty acids, C8-10, C12-18-alkyl esters
MW	368.7 g/mol	312.53-424.74 g/mol
Repeated dose toxicity, oral	RA: CAS 95912-86-0	NOAEL: 1000 mg/kg bw
Repeated dose toxicity, inhalation	-	-
Repeated dose toxicity, dermal	-	-

 

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Hexadecyl 2-ethylhexanoate (CAS No. 59130-69-7).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Toxicity after long-term exposure is assessed by use of a subacute oral toxicity study with Fatty acids, C8-10, C12-18-alkyl esters, which was performed in male and female Wistar rats similar to OECD guideline 407 under GLP conditions (Pittermann, 1993). Rats were allocated to main control and treatment (10 rats per group) and satellite control and treatment (5 rats per group) groups. The rats were dosed with 100, 300, and 1000 mg/kg bw of the test substance by oral gavage. They were dosed once daily, 5 days/week for 28 days, resulting in 23-24 doses in total. There was no substance-related mortality and no clinical signs were observed during the study period. No effect on body weight gain was observed. Food and water consumption were similar in the control and treatment groups. Ophthalmoscopic examination revealed no effects. The males administered 1000 mg/kg bw/day had a significant increase in the level of leucocytes with segmented nuclei. As this effect was only observed in one sex and there were no other haematologic or histopathologic effects, this was not considered to be a treatment-related effect. No treatment-related effects on organ weights and clinical chemistry were observed. 1/10 females administered 1000 mg/kg bw/day had severe oedema in the forestomach and 1/10 had thickening of the forestomach mucosa. No other effects were noted during necropsy. Histopathology revealed that 4/10 males and 2/10 females in the 1000 mg/kg bw/day group had oedema in the mucosa of the forestomach, and the 2 females also had ulcerations. The findings in the forestomach were probably compound-related, however, humans do not have a forestomach and this effect is therefore not relevant to human exposure. As none of the animals in the satellite group had effects on the forestomach, this is considered to be a reversible effect. In conclusion, no adverse effects were observed after treatment of Wistar rats with up to 1000 mg/kg bw Fatty acids, C8-10, C12-18-alkyl esters. Thus, a NOAEL of 1000 mg/kg bw was deduced. 

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
There is only one study available.

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for repeated dose toxicity, no classification is required.