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Description of key information

RA-S, CAS 68424-31-7, Key, Croda, Brammer, 1993, rep. dose, 28 d, oral, RL1 - NOAEL 1450 mg/kg/d

Key value for chemical safety assessment

Additional information

Repeated dose toxicity oral:

There were no repeated-dose studies conducted with the fatty acid polyol with CAS No. 85116-93-4 (Fatty acids, C16-18, esters with pentaerythritol), therefore data of a study from a structural analogue, conducted according to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents), was used for read-across.

Fatty acids, C5-10, esters with pentaerythritol (CAS No.: 68424-31-7), was administered in concentrations of 0 ppm, 1000 ppm, 5000 ppm, 12500 ppm (resembling 112 mg/kg bw/d, 562 mg/kg bw/d and 1450 mg/kg bw/d for male and 119 mg/kg bw/d, 586 mg/kg bw/d and 1613 mg/kg bw/d for female rats, respectively) to 5 animals per sex and dose. No effects on body weight, clinical signs, haematological parameters and in clinical chemistry were observed. Increased kidney weight, increased tubular hyaline droplet formation and tubular basophilia and granular cast formation was found. Hepatocyte hypertrophy in the highest dose group was considered to be an adaptive response, not an adverse effect. Treatment related changes in male rats are considered not relevant for human and were therefore not employed for NOEL determination. A NOAEL of 1450 and 1613 mg/kg/d could be identified for male and female rats, respectively (RA-S, CAS 68424-31-7, Key, Croda, Brammer, 1993, rep. dose, 28 d, oral, RL1).

 

Fatty Acid Polyols are deemed to be substances of low toxicity. The dermal and inhalative absorption is considered to be low due to their physico-chemical properties (log Kow >4, low water solubility and high molecular weight). Once absorbed, they are stepwise hydrolysed to carboxylic (e.g. fatty) acids and polyols. Linear carboxylic acids feed into physiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis. The polyols are very polar (log Kow<-2) and do not accumulate in the body but are readily excreted via urine. Alternatively, one or several hydroxyl groups can be oxidized to a carboxylic acid moiety prior to urinary excretion.

 

The available study on oral repeated dose toxicity supports the view that Fatty Acid Polyols including CAS No. 85116-93-4 (Fatty acids, C16-18, esters with pentaerythritol) are substances of low toxicity.

 

Repeated dose toxicity dermal:

There were no dermal repeated dose toxicity studies on Fatty Acid Polyols available. The dermal and inhalative absorption is considered to be low due to their physico-chemical properties (log Kow >4, low water solubility and high molecular weight). It can be assumed that Fatty Acid Polyols are non-toxic substances following dermal exposure, as there was no systemic toxicity observed upon oral exposure and no skin or eye irritation. Since no route-specific metabolism/toxicity is expected to occur, the oral NOAEL can be used to derive a DNEL for the dermal route.

Taking into account this result of the oral 28 d study and the physicochemical properties of fatty acid polyols and with respect to the animal welfare, the conduction of a sub-chronic dermal study (90 d) is scientifically not justified (see Waiver: Repeated does toxicity: dermal).

 

Repeated dose toxicity inhalation:

No repeated dose toxicity studies conducted with Fatty Acid Polyols applied per inhalation were available.

Most Fatty Acid Polyols are liquid substances. The vapour pressure of Fatty Acid Polyols is <0.01 Pa at room temperature, therefore the respiration of vapour can be excluded. Nevertheless respirable aerosols can occur due to the use of fatty acid polyols in spray applications (see chapter 3).

However, Fatty Acid Polyols are non-toxic substances following acute inhalation of aerosol. Carboxyesterases and ubiquitously expressed lipases are expressed in the lung catalysing the hydrolysis of the ester bonds. The likelihood of persistence in the lung is considered to be negligible. The free fatty acid and the respective polyols are likely to be taken up by the alveolar epithelium.

Taking into account this result of the oral 28 d study and the physicochemical properties of fatty acid polyols and with respect to the animal welfare, a sub-chronic dermal 90 d study is scientifically not justified (See Waiver: Repeated dose toxicity: inhalative).

Justification for classification or non-classification

According to the DSD and CLP criteria for classification and labelling of dangerous substances CAS No. 85116-93-4 (Fatty acids, C16-18, esters with pentaerythritol) is not classified as toxic after repeated application.