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Description of key information

Short-term repeated dose toxicity: oral (read-across, equivalent/similar to OECD 407): NOAEL >= 1000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects
Remarks on result:
other: Source: CAS 189120-64-7, Exxon, 2000
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
300 mg/kg bw/day (actual dose received)
System:
urinary
Organ:
kidney
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
no

An increased amount of hyaline droplets 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. This phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man.

Conclusions:
In an oral short-term (28-day) repeated dose toxicity study with an adequate analogue source substance, a NOAEL of >= 1000 mg/kg bw/day was obtained, representing the highest dose tested. As explained in the analogue justification, this result is considered to be valid also for the target substance.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study from a source substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profiles. The selected study is thus sufficient to fulfil the standard information requirements set out in Annexes VIII - X, Item 8.6, in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH).

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

No data on the short-term (28-day) repeated dose toxicity for the target substance neopentyl glycol dicaprate (CAS 27841-06-1) are available. Therefore, the repeated dose toxicity endpoint was assessed based on data from the analogue source substance fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7).

A 28-day oral repeated dose toxicity study with fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) was performed according to OECD guideline 407 and under GLP conditions (Exxon, 2000). Groups of five male and five 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 (five per sex and dose) received the concurrent vehicle, peanut oil. Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology parameters, clinical chemistry parameters, organ weights, neurobehaviour, gross necropsy and histopathology. No mortality was observed during the study period. Female animals tolerated the daily oral administration of the test substance without any toxicologically relevant adverse effects up to the high dose of 1000 mg/kg bw/day. In male animals adverse effects were observed in the histopathology examination. 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 to be 1000 mg/kg bw/day for male and female rats.

The available data indicate a low level of short-term (28-day) repeated dose toxicity after oral application for the source substance. Therefore, no hazard for oral repeated dose toxicity is expected for the target substance.

Justification for classification or non-classification

The available data on short-term (28-day) oral repeated dose toxicity of the analogue source substance fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) do not meet the classification criteria according to the CLP Regulation (EC) No. 1272/2008. Based on read-across, also no classification is warranted for the target substance neopentyl glycol dicaprate (CAS 27841-06-1). Data are, therefore, conclusive but not sufficient for classification.

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