Registration Dossier

Administrative data

Description of key information

Studies are available for read-across substances in the rat (28-day, 6-month, 2-year) and dog (6-month).  The studies are consistent in that they do not identify any adverse effects of the test materials even at very high dose levels.

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
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
A number of studies of variable quality are available in the rat and dog, covering expousre durations of 28-days to 2 years. The studies consistently do not identify any adverse effects even at very high dose levels.

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

The registered substance consists of mixed tri-esters of C18, C20 and C22 fatty alcohols and citric acid. Studies performed with mixed (i.e. mono-, di- and tri-) stearyl (C18) esters in the rat indicate that the intact substance is not absorbed following oral administration, but that some gastrointestinal enzymic hydrolysis may occur at low dose levels. The level of hydrolysis in the dog was noted to be higher than that seen in the rat, but was still incomplete. Following oral administration of the registered substance, systemic exposure to the hydrolysis products (i.e. C18, C20, C22 fatty alcohols and citric acid) can be predicted; data available from the repeated dose toxicity studies with behenyl (C22) alcohol indicate rapid absorption in the rat and dog, but also suggest that may be incomplete at high dose levels. Citric acid is present in the body as a metabolic intermediate; fatty alcohols are converted to the respective fatty acid in enterocytes on absorption and subsequently incorporated into hepatic fatty acid metabolism

A 28 -day study performed with the related fatty alcohol citrate ester does not reveal any effects of treatment at 1000 mg/kg bw/d. A similar absence of toxicity is observed in a 6-month toxicity study in the rat performed with the hydrolysis product behenyl alcohol at dose levels of up to 1000 mg/kg bw/d. Effects of treatment in a 6-month dog study performed with behenyl alcohol at dose levels of up to 2000 mg/kg bw/d were limited to pale faeces; this finding indicates the presence of unabsorbed test material and is not considered to represent an adverse effect. A 2-year rat study performed with mixed stearyl citrate esters did not reveal any effects of treatment at a dietary concentration of 10% (10,000 ppm; equivalent to 5000 mg/kg bw/d). This mixture of esters contained 12.5% tri-stearyl citrate (equivalent to 625 mg/kg bw/d); the other constituents of this material (i.e. the mono- and di-stearyl esters of citric acid) are considered likely to represent a worst-case with respect to hydrolysis and subsequent systemic exposure to fatty alcohol.

The results of a number of repeated dose toxicity studies performed with read-across substances (related esters and hydrolysis products) therefore show that the registered substance is of very low toxicity following and indicate that adverse effects of exposure are unlikely, even at the limit dose.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
This modern GLP-compliant study was performed in the preferred species, the rat.

Justification for classification or non-classification

No classification for repeated dose toxicity (STOT-RE) is proposed accoridng to the CLPR Regulation. The data demonstrate that the substance is likley to be of very low toxicity.