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Administrative data

Description of key information

No treatment-related or biologically relevant findings in rats following repeated exposure to the two main constituents and/or trlated materials.

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
799 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

Sufficient iformation exists to characterise the repeated dose toxicity of distilled tall oil fatty acids.

The maleate salts are formed when the fatty acids or rosin acids react with maleic anhydride.

The available data includes results obtained from testing Rosin, fumarated and fatty acids, C14-18 and C16-18-unsatd., maleated, and is summarised below.

Rosin, fumarated was administered in the diet to male and female rats at concentrations of 0, 1000 ppm, 3000 ppm and 10000 ppm for approximately 6-7 weeks. Food consumption and mean body weights were decreased in both sexes at 10000 ppm and 3000 ppm, with high dose animals also showing an increase in total bilirubin (both sexes) and decreased adrenal weight (females only).  The lower of these two values will be used as the NOAEL for the repeated dose toxicity. This is considered a scientifically defensible since, apart from poor palatability and associated body weight reduction following exposure to 10000 ppm test substance, no clearly adverse effects were apparent. The NOAEL for repeated dose toxicity of Rosin, fumarated  is therefore 221-228 mg/kg bw/d for males and 196-292 mg/kg bw/d for females.

In a key combined repeat dose reproductive/developmental toxicity study, the test material (Fatty acids, C14-18 and C16-18-unsatd., maleated) was administered daily via oral gavage at doses of 0, 100, 300, and 1000 mg/kg bw/day to Wistar rats (12/sex/dose) in a propylene glycol vehicle. Male rats were treated for a period of 35 days (14 days pre-mating, 14 days mating/post-mating period followed by an additional week) while female rats were treated for approximately 47 days (14 days pre-mating, for up to 7 days mating period, through gestation til PPD 4). A satellite group of nulliparous and non-pregnant female rats (5/sex/dose) was also employed in the study and treated with the test material for a period of 35 days. No signs of mortality or clinical toxicity were observed through the study period. Body weight and food consumption remained unaffected post-treatment with the test material. Effects on prothrombin time in mid and high dose groups were observed but not considered toxicologically significant. Clinical chemistry, urinalysis, and neurobehavioral parameters appeared unaffected through the study period. Slightly lower kidney weights were recorded for males at 300 and 1000 mg/kg bw/day (Mid and High dose). The changes were not associated with any findings in clinical pathology or microscopic changes and were regarded as physiological variation. Test material related microscopic findings were found at 1000 mg/kg bw/day (High dose) in stomach, in the form of hyper/paraceratosis of the nonglandular gastric mucosa. This minimal to mild multifocal change occurred in 4 of 5 males and 2 of 5 females. There were no microscopic findings related to treatment at 100 or 300 mg/kg bw/day. These findings are indicative of local irritation and analogous structures do not exist in man. Necroscopy did not reveal any remarkable findings.

 

Based on the observations of this subacute oral toxicity study, the NOAEL was determined to be 1000 mg/kg bw/day.

In a supporting range finding repeat dose toxicity study, the test material (Fatty acids, C14-18 and C16-18-unsatd., maleated) was administered via oral gavage at doses of 0, 100, 300, and 1000 mg/kg bw/day to Wistar rats (5/sex/dose) in a propylene glycol vehicle, daily for a period of 7 days.

No signs of mortality or clinical toxicity were observed through the study period. Body weight and food consumption remained unaffected post-treatment with the test material. Necroscopy did not reveal any remarkable findings. Hematology parameters were observed to be affected. However, no clear dose- or test-material related correlation could be established. Increases in differential monocyte count and serum creatinine and potassium levels were observed at 1000 mg/kg bw/day), however, whether these variations were attributable to treatment with the test material remained unclear under the conditions of this preliminary study. Based on the observations of this preliminary range finding study the NOAEL was determined to be 1000 mg/kg bw/day.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
estimated NOAEL based on data available for the two main constituents and/or related materials. Pro-rata calculation.

Justification for classification or non-classification

Not classified for specific target organ toxicity – repeated exposure according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 orUN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).