Isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester

Endpoint summary

Description of key information

Oral: OECD 407, rat, NOAEL (m/f) =1450/1613 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 450 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) and consistent studies, from reference substances 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 read-across

There are no data available for the repeated dose toxicity of isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester (CAS 109884-54-0). 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 the 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 comparable pattern as a result of structural similarity, the substances fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) and fatty acids, C7, C8, C10 and 2-ethylhexanoic acid, tetraesters with pentaerythritol (CAS 68424-31-7) are selected as source substances.

 

Repeated dose toxicity: oral

CAS 189120-64-7

A 28-day oral feeding toxicity study with Fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) was performed equivalent or similar to OECD guideline 407 and under GLP conditions (Trimmer, 2000). Groups of 5 male and 5 female Cr:CD BR rats were exposed to the substance at 100, 300 and 1000 mg/kg bw/day by gavage, 7 days/week for 28 days. Control animals (5 per sex and dose) received the concurrent vehicle, peanut oil. Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, neurobehaviour, gross necropsy and histopathology. Female animals tolerated the daily oral administration of the test substance without any adverse effects (included mortality) up to the high dose of 1000 mg/kg bw/day. In male animals no adverse effects were observed for all investigated parameters except for histopathology. An increased amount of hyaline droplets (the main constituent of which is alpha-2µ-globulin) in the proximal cortical tubular epithelium was confirmed microscopically in the cytoplasm of the renal cortical tubular epithelial cells in male rats treated with 300 and 1000 mg/kg bw/day, respectively. As this phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man, the 28-day oral NOAEL, for Fatty acids, C7-8, triesters with trimethylolpropane was found 1000 mg/kg bw/day for male and female rats.

 

CAS 68424-31-7

Furthermore, a 28 day study with Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) was conducted equivalent or similar to OECD guideline 407 and under GLP conditions (Brammer, 1993). The test substance was administered in concentrations of 1000 ppm, 5000 ppm and 12500 ppm (corresponding to 112, 562 and 1450 mg/kg bw/day for male and 119, 586 and 1613 mg/kg bw/day for female rats) to 5 Alpk:APfSD rats per sex and dose for 28 consecutive days. Control animals (5 per sex and dose) received the plain diet. There were no toxicologically significant effects on body weight, food consumption and clinical condition and mortality up to and including the highest dose level. Changes in clinical chemistry and red cell-related parameters were observed in male rats at 12500 ppm, but these were minor and considered not to be of toxicological significance. A minimal hepatocyte hypertrophy present in males of the 12500 ppm group was observed and considered to be evidence of an adaptive response. Microscopic examination of the kidneys from male animals from all dose groups revealed an increase in hyaline droplet formation (the main constituent of which is alpha-2µ-globulin) and tubular basophilia. This phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man. A NOAEL of 1450 and 1613 mg/kg/d could be identified for male and female rats, respectively.

 

Conclusion for repeated dose toxicity

The data for the source substances showed that no effects were observed up to and including the recommended limit values in studies conducted via the oral route. No information on repeated dose toxicity is available for the inhalation and dermal routes. Therefore, as the available data did not identify any hazard for repeated dose toxicity, isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester is not expected to be hazardous following repeated exposure. 

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 substance and overall assessment of quality, duration and dose (refer to the endpoint discussion for further details).

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 isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester, data will be generated from data for 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.