Bis(C12-C13)alkyl-2-hydroxybutandioate

Endpoint summary

Description of key information

In experimental conditions, on the basis of a total evaluation of the results obtained, the test material bis(C12-C13)alkyl-2-hydroxybutandioate did not cause any local or general toxicity after subacute dermal exposition (28 d) in rabbits. The NOAEL was determined to be 10 mL/kg bw/day (1000 mg/kg bw/d). 
The inhalative study is waived because the substance has a veryl low  vapour pressure (0.0000000026 Pa at 25 °C), so the potential for the generation of inhalable forms is low.
The most critical NOAEL for the read-across substance di-2 -ethylhexyl adipate (please see 7.1.1) was observed in the one-generation study (170 mg/kg bw/day - effects on the offspring: reduced total litter weight and reduced mean litter size). At the same time, this is the lowest NOAEL determined in repeated dose toxicity studies. This value will be taken for derivation of the DNELs for bis(C12-C13)alkyl-2-hydroxybutandioate.
 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

170 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

The study of subacute dermal toxicity (28 days) was performed on a group of 30 rabbits (20 treated and 10 controls) according to Directive 92/69/EEC.

The test material, bis(C12 -C13)alkyl-2 -hydroxybutandioate, was administered for 4 weeks (5 days out of 7) at daily dose of 10 mL/kg bw (1000 mg/kg bw/d) by dermal application. The test material was administered undiluted to 20 animals, while the control group (10 animals) were treated with sesame seed oil.

The results obtained from the study can be summarized as follows: No case of mortality and no pathological symptoms were observed in the animals treated and in the control animals, in particular no phenomena of erythema or oedema was observed in the area where the test material was applied.

At the autopsy no pathological anomalie were observed. The weight of the organs showed no significant differences between the 3 groups. The hematological and hematochemical examinations, conducted at the end of the study did not show any significant differences between the groups.

In experimental conditions, on the basis of a total evaluation of the results obtained, the test material bis(C12-C13)alkyl-2-hydroxybutandioate did not cause any local or general toxicity.

The substance has very low vapour pressure (0.0000000026 Pa at 25 °C), so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore the results of laboratory animal studies show low acute oral and low acute and subacute dermal toxicity for the substance. This intrinsic property/toxicity potential can be extrapolated to inhalative route administration.

In an oral chronic rat-study with the metabolite malic acid the LOAEL was 50000 ppm and the NOAEL 5000 ppm. In the high-dose group were the major effects decreased body weight gain and decreased feed consumption.

For the metabolite C12, 13 -Alcohols we have a subacute study with an oral NOAEL of 300 mg/kg bw/day (Sasol, 1993). This study is criticized because the effects seen in this study are not ascribed to a dose response effect but rather are associated with the method of dosing. A read-across from a reliable 13-week dietary study in rats using Hexanol reported a NOAEL of 1127 mg/kg bw/day and no adverse effects were noted at any of the dose levels administered during the study (Scientific Associates Inc. 1966).

For the read-across substance di-2 -ethylhexyl adipate (please see 7.1.1), several valid studies concerning repeated dose toxicity are available. Besides a 28 day oral study (Miyata, 2006), the substance was investigated by NTP in subchronic and chronic studies in two species (rat and mouse) (NTP, 1982). In addition, there is an oral one-generation reproduction toxicity study with an exposure period of 10 weeks for parental animals (Cefic, 1989). The most critical NOAEL was observed in the one-generation study (170 mg/kg bw/day - effects on the offspring: reduced total litter weight and reduced mean litter size). At the same time, this is the lowest NOAEL determined in repeated dose toxicity studies. This value will be taken for derivation of the DNELs for bis(C12-C13)alkyl-2-hydroxybutandioate.

Justification for classification or non-classification

No classification for repeated dose toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (67/544 EEC) or the classification, labeling and packaging (CLP) regulation (EC 1272/2008).