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Description of key information

A 28 -day study (Jones, 2000) with the structural analogue Dipentaerythritol ester of nC5/iC9 acids 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 DiPE triisononanoate triethylhexanoate (CAS 68443-84-5). 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, 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

68443-84-5

647028-25-9

Chemical name

DiPE triisononanoate triethylhexanoate

Dipentaerythritol ester of nC5/iC9 acids

MW

1053.6 g/mol

983-1096 g/mol

Repeated dose toxicity, oral

RA: CAS 647028-25-9

Experimental result: 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 forDiPE triisononanoate triethylhexanoate(CAS 68443-84-5).

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

Furthermore, based on exposure considerations no further data for the endpoints “Repeated dose toxicity” and “Toxicity to reproduction” were included in the dossier. In order to put the main focus on human health, a very conservative approach was followed. The exposure assessment is based on the reproductive toxicity of 2 -ethylhexanoic acid, which is assumed to be the most sensitive endpoint (LOEL = 100 mg/kg bw/day for reproductive toxicity). No further adverse effects after repeated exposure of the test substance itself is supposed. This is supported by a subchronic toxicity study (Jones et al., 2000) with the analogue substanceDipentaerythritol ester of nC5/iC9 acids(CAS647028-25-9),where no adverse effects were found revealing a NOAEL of 1000 mg/kg bw (highest dose tested).

Discussion

A subacute oral toxicity study with Dipentaerythritol ester of nC5/iC9 acids is available, which was performed in male and female Sprague-Dawley rats according to OECD guideline 407 and in compliance with GLP (Jones et al., 2000). Rats were allocated to control and treatment groups (5 rats per sex and group) and were dosed with 150, 500, and 1000 mg/kg bw/day of the test substance by gavage. They rats were dosed once daily, 7 days/week for 28 days. There was no substance-related mortality and no clinical signs that were related to treatment were observed during the study period. No effect on body weight gain was observed. No treatment-related effects were observed regarding organ weight, clinical chemistry and pathology. Three males treated with 1000 mg/kg/day demonstrated globular accumulations of eosinophilic material in the proximal tubular epithelium which should be regarded as a possible effect of treatment. The authors considered this finding consistent with the appearance of hydrocarbon nephropathy, which results from the excessive accumulation of α2-microglobulin in renal proximal tubular epithelium of adult male rats, which does not represent a hazard to human health.

In conclusion, no adverse effects were observed after treatment of Sprague-Dawley rats with up to 1000 mg/kg bw/day Dipentaerythritol ester of nC5/iC9 acids. Thus, a NOAEL of 1000 mg/kg bw/day 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.