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Administrative data

Description of key information

RA-S, CAS 68424-31-7, Key, Croda, Brammer, 1993, rep. dose, 28 d, oral, RL2 - NOAEL 909.85 mg/kg bw/d (this value is based on the NOAEL of 1450 mg/kg bw/d of the original study and adapted to the molecular weight of the test substance)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
909.85 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Repeated dose toxicity oral:

There were no repeated-dose studies conducted with the fatty acid polyol with CAS No. 68424-30-6 (Fatty acids, C5-9, 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.

A 28 d study was conducted according to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents).

Fatty acids, C5-10, esters with pentaerythritol (CAS No.: 68424-31-7), were 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 for 28 consecutive days. There were no toxicologically significant effects on body weight, food consumption and clinical condition up to and including the highest dose level. Changes in some 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. There were no clinical signs indicative of neurological dysfunction in any of the treatment groups, nor was there any evidence of neuropathological changes in the brains of the 12500 ppm group. A minimal hepatocyte hypertrophy, present in males in the 12500 ppm group, is 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 and 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 (RA-S, CAS 68424-31-7, Key, Croda, Brammer, 1993, rep. dose, 28 d, oral, RL2).

 

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.

68424-30-6 (Fatty acids, C5-9, esters with pentaerythritol) are substances of low toxicity.

With regard to the molecular weight ratio of both substances and in a worst case assumption (male NOAEL and highest possible molecular weight for CAS-No. 68424-31-7), the NOEL used for the calculation of DNELs was adapted for CAS No. 68424-30-6.

 

The molecular weight of Fatty acids, C5-9, esters with pentaerythritol (CAS No. 68424-30-6) is 472.62 - 697.04 g/mol, the molecular weight of Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) is 472.62 - 753.2 g/mol.

 

An conversion factor of 472.62 g/mol/753.2 g/mol = 0.63 was applied.

 

NOAEL(oral) (CAS-No. 68424-30-6) = NOAEL(oral) (CAS-No. 68424-31-7) x 0.63

= 1450 mg/kg bw/d x 0.63 = 909.85 mg/kg bw/d. This value was used as basis for DNEL (systemic, long term) -calculation.

Repeated dose toxicity dermal:

There were no dermal repeated dose toxicity studies on Fatty Acid Polyols available.

 

Repeated dose toxicity inhalation:

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

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.

68424-30-6 (Fatty acids, C5-9, esters with pentaerythritol) is not classified as toxic after repeated application.