Registration Dossier

Administrative data

Description of key information

Read Across substance 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS No. 68442-70-6): 
- subchronic (90 day) NOAEL of 68 mg/kg bw/d and 75 mg/kg bw/d was found for male and female rats
- subchronic (90 day) LOAEL of 683 mg/kg bw/d and 772 mg/kg bw/d was found for male and female rats

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
68 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarity between the source and target substance.

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 only limited data available on the repeated dose toxicity of 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.4, 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.

Overview of repeated dose toxicity

CAS

Repeated dose toxicity oral

Repeated dose toxicity inhalation

Repeated dose toxicity dermal

90193-76-3 (a)

RA: CAS 68442-70-6

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68442-70-6 (b)

Subchronic: NOAEL of 68 mg/kg bw/day and 75 mg/kg bw/day for male and female rats

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(a) The substance subject to registration is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substance is 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 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

CAS 90193-76-3

A 90 day oral feeding study with 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS No. 68442-70-6) was performed equivalent to OECD Guideline 408 in male and female CFY rats (Rivett, 1972). The test substance was mixed at concentrations of 0, 500, 1,000 and 10,000 ppm to the diet and groups of 10 animals per sex were fed ad libitum for 13 weeks. The group mean intakes as calculated from group mean bodyweight and food consumption were 0, 34, 68 and 683 mg/kg bw/day for male and 0, 39, 75 and 772 mg/kg bw/day for female rats.

At the highest dose the following abnormalities were observed: two deaths among male rats, slight depression of body weight gain in males and females, marginally reduced food consumption in males, increased serum AP levels in males and females, changes consistent with internal haemorrhage at terminal autopsy in males, slightly increased thyroid weights in males, haemorrhage and associated chronic inflammatory reaction in the pancreas and areas of fat throughout the body in males. Treatment at 500 and 1000 ppm were without overt adverse effects.

Thus, the subchronic NOAEL was set to be 68 mg/kg bw/day for male and 75 mg/kg bw/day for female and the LOAEL was set to be 683 mg/kg bw/day for male and 772 mg/kg bw/day for female rats. It can be assumed, that the subchronic NOAEL for the test substance could have been higher than the values identified in this study - under the aspect, that the middle dose level was only one tenth of the highest dose level.

 

Conclusions for repeated dose oral toxicity

There are no data available on repeated dose toxicity of 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). However, the tested read across substance 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters is very similar to 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters and has identical molecular weight. Based on these results, the NOAEL was established at 68 and 75 mg/kg bw/day for male and female rats and the LOAEL was etablished at 683 and 772 mg/kg bw/day for males and female rats.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substances and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

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