Fatty acids, C14-18 and C16-18-unsatd., maleated

Endpoint summary

Description of key information

Repeated dose toxicity of the test item (structural analogue) was determine din the course of a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening study (OECD 422, GLP). Oral administration by gavage male and female Wistar rats did not reveal signs of toxicity. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d in both sexes. 

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:

subacute

Species:

rat

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

Read across justification

The test item is an UVCB and composes mainly of modified fatty acids from sun flower oil (mSOFA) and, to a minor part, of modiefied fatty acids from tall oil (mTOFA). The fatty acids obtained from tall oil and sun flower oil are of comparable chain lenghth and are modified by the same reaction step. In contrast to mTOFA, mSOFA is also produced solely by the very same reaction as the UVCB and consists therefore of the same reaction products and similar impurities. Furthermore, mSOFA was intentively examined for its toxicological properties. Thus, it is acceptable to derive data on acute toxicity from the read across substance mSOFA.

read across substance CAS 1309959 -24 -7

The test item was administered orally by gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0 mg/kg body weight/day (PEG 300 served as vehicle), 100 mg/kg bw/d, 300 mg/kg bw/d and 1000 mg/kg bw/d. The duration of treatment covered a 2-week premating and a mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and 2 weeks thereafter in females. A detailed clinical observation was performed in all animals. Body weights and food consumption were determined in F0 animals. Clinicochemical and hematological examinations as well as urinalyses and FOB were performed in all animals towards the end of the administration period. All animals were assessed by gross pathology; weights of selected organs were recorded and a histopathological examination was performed.

All animals survived until scheduled day of necropsy. Food consumption and body weight, pathology, FOB were without any findings.

In animals of both genders treated at 1000 mg/kg bw/day, a statistically significant reduction in total bilirubin was noted. A trend towards reduced values was also be observed in males at 300 mg/kg bw/day. The alterations in bilirubin were considered to be of no toxicological relevance. At the dose level of 300 and 1000 mg/kg bw/day, bedding in mouth was noted for all males and females. This finding was considered to be a sign of discomfort and without toxicological relevance. The test item induced minimal hepatocellular hypertrophy in the liver at ≥300 mg/kg bw/day and minimal diffuse follicular cell hypertrophy in the thyroid gland at 1000 mg/kg bw/day in individual males. The liver cell hypertrophy was considered to be an adaptive change consequent to enhanced metabolic challenge with sustained microsomal enzyme induction resulting in centrilobular hepatocellular hypertrophy. It is suggestive that the long-term stimulation of the hypothalamic-pituitary-thyroid axis secondary to the increased clearance of thyroid hormones in the liver is likely correlated with consequent thyroid follicular cell hypertrophy in single males at 1000 mg/kg bw/day. The thyroid gland is highly sensitive to this phenomenon in rats which is particularly species-specific with no safety relevance for humans.

Thus, under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test the oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d in both sexes.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for repeated dose toxicity under Directive 67/548/EEC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008.