Reaction mass of ethoxylated N-oleyl-1,3-propanediamine, hydrofluorides of and ethoxylated N-palmityl-1,3-propanediamine, hydrofluorides of and ethoxylated N-stearyl-1,3-propanediamine, hydrofluorides of and olaflur

Endpoint summary

Description of key information

In chronic toxicity studies amine fluorides (mixture of 1.315 % Olaflur as leading substance and 0.347 % Hetaflur) were administered to Long-Evans rats and to Beagle dogs, respectively. For the two tested species the NOAEL was considered to be 1 mg/kg bw/day, both for males and females.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 mg/kg bw/day

Additional information

Olaflur was not tested for oral repeated dose toxicity as pure substance. Instead a read-across approach was performed with test substance Amine fluoride 297/242, a mixture consisting of Olaflur (Amine fluoride 297) and Hetaflur (Amine fluoride 242), a structural analogue of Olaflur, at a ratio of about 3.8 : 1.

Chronic, oral (rat):

In a chronic toxicity study amine fluorides (mixture of 1.315 % Olaflur as leading substance and 0.347 % Hetaflur) were administered to 70 Long-Evans rats per sex per dose in diet at dose levels of 0, 1, 5 or 25 mg/kg bw/day for a period of 2 years (Menley & James Laboratories, 1975). The NOEL was considered to be 1 mg/kg bw/day for both males and females.

No fatalities occurred during the study. From 6 months after study begin onwards, some of the animals of the 5 and 25 mg/kg bw/d groups showed stiffening of several joints of the fore or hind paws, and of knees and tails, indicating a beginning osteosclerosis. An increase in the leucocyte count was found in male rats of the high-dose group, and – to a lesser extent – in the females of the same group. A dose-dependent enlargement of the mesenteric lymph nodes and yellowish discoloration of the small intestines were seen in the 5 and 25 mg/kg bw/day groups, indicating hypertrophy of the reticulo-endothelial system in response to phagocytosis of the amine fluorides at the site of their absorption.

Chronic, oral (dog):

In a chronic toxicity study amine fluorides (mixture of 1.315 % Olaflur as leading substance and 0.347 % Hetaflur) were administered orally per intubation to 6 Beagle dogs per sex per dose at dose levels of 0, 1, 5 or 25 (10) mg/kg bw/day for a period of 2 years ( Menley & James Laboratories, 1975). The NOEL was considered to be 1 mg/kg bw/day for both males and females.

After 5 weeks, the high dose (25 mg/kg bw/day) was reduced to 10 mg/kg bw/day because of intolerance. Animals of the high and middle dose group showed reduced body weight gains. At the end of treatment slightly lower serum phosphate levels were determined as compared to the controls. On dissection, a yellowish discoloration and hyperplasia/hypertrophy of the reticulo-endothelial system was seen. No other macroscopic or microscopic changes were found in the organs and tissues.

Chronic, dermal:

No studies are available to assess toxicity after repeated dermal exposure, however DNELs can be derived for oral toxicity studies.

Chronic, inhalation:

No studies are available to assess toxicity after repeated inhalation exposure, however DNELs can be derived for oral toxicity studies.

Justification for classification or non-classification

Amine fluorides containing Olaflur as leading substance did not induce adverse effects indicative of serious damage at dose levels relevant for classification and labelling when tested for oral repeated dose toxicity. Therefore the test item is not subject to classification and labelling for repeated dose toxicity according to Directive 67/548/EEC (DSD) and Regulation (EC) No. 1272/2008 (CLP).