Hexanedioic acid, di-C16-18 (even numbered) alkyl esters

Endpoint summary

Description of key information

Oral (similar to OECD 408), rat: NOAEL = 630/2187 mg/kg bw/day (m/f)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

630 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex XI, 1.5, 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 on the repeated dose toxicity ofHexanedioic acid, di-C16-18 (even numbered)alkyl esters (CAS 92969-90-9).In order to fulfil the standard information requirements set out in Annex VIII, 8.6, 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, Item 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 (oral)

CAS 103-23-1

A subchronic oral toxicity study equivalent or similar to OECD 408 was performed with Bis(2-ethylhexyl) adipate (CAS 103-23-1) in Fischer 344 rats at dose levels of 1600, 3100, 6300, 12500 and 25000 ppm for a period of 90 consecutive days (NTP, 1982). This is equivalent to 140, 271, 551, 1094 and 2187 mg/kg bw/day in females, and 160, 310, 630, 1250 and 2500 mg/kg bw/day in males, respectively. Ten animals per sex and dose received the test substance daily via diet, whereas a similar constituted control group was administered the plain diet. There was no mortality, and no clinical signs were observed in any of the animals during the study period. The body weight gain was significantly reduced in males at 12500 and 25000 ppm (≥ 11%), compared with the control group. The average food consumption was similar between treated and control groups of both males and females. No adverse effects were noted at histopathological examination in male and female rats. No clinical chemistry or haematological parameters were assessed in this study. In male rats, the NOAEL was set at 6300 ppm, which was equivalent to a dose of 630 mg/kg bw/day. In female rats, the NOAEL was set at 25000 ppm, which was equivalent to a dose of 2187 mg/kg bw/day.

 

Conclusion for repeated dose toxicity

The data for the source substance showed that systemic effects were observed in male rats exposed via the oral route at doses above the currently recommended limit dose. No information on repeated dose toxicity is available for the inhalation and dermal routes. Therefore, as no hazard for repeated dose toxicity was identified in the source substance, Hexanedioic acid, di-C16-18 (even numbered)-alkyl ester is not expected to be hazardous following repeated exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Hexanedioic acid, di-C16-18 (even numbered)-alkyl esters, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

Therefore, based on the analogue read-across approach, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.