A mixture of: 2,2',2'',2'''-(ethylenedinitrilotetrakis-N,N-di(C16)alkylacetamide; 2,2',2'',2'''-(ethylenedinitrilotetrakis-N,N-di(C18)alkylacetamide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

oral

In a 1-generation study conform to GLP requirements and to OECD test guideline 415, KEROFLUX ES 3241 was administered as an oily emulsion/solution to groups of 25 male and 25 female sexually immature Wistar rats (F0 parental generation) by stomach tube at dosages of 100, 300 or 1000 mg/kg bw/day continuously throughout the whole study period. A standard dose volume of 5 ml/kg bw was used. The control group, consisting of 25 males/25 females was dosed with the vehicle only (olive aul DAB 10). At least 70 days after the beginning of treatment, F0 animals were mated to produce one litter (F1). Mating pairs were from the same dose group. The study was terminated with the terminal sacrifice of the F1 weanlings and F0 adult animals.

Food consumption of the F0 parents was determined regularly during premating (once weekly), and additionally during gestation and lactation periods. In general, body weights of F0 parents were determined once weekly. However, during gestation and lactation F0 females were weighed on days 0, 7, 14 and 20 of gestation, on the day of parturition, and on days 1, 4, 7, 14 and 21 after birth.

The F1 pups were weighed on the day after birth and on days 4, 7, 14 and 21 post partum. The parents' and the pups' state of health was checked each day, and parental animals were examined for their mating and reproductive performances. Pups were sexed and monitored with respect to their development stages and their behavior was assessed in certain tests. Their viability was recorded. All pups were exainined macroscopically at necropsy; if necessary, certain pups were additionally inspected for any organ/skeletal findings.

Blood and urine samples were taken from 10 F0 animals per sex of each test group towards the end of the study period for clinical pathology examinations. All F0 parental animals were assessed by gross pathology (including weight determinations of several organs) and subjected to an extensive histopathological examination, special attention being paid to the organs of the reproductive system.

The oral administration of KEROFLUX ES 3241 to male and female rats in this one generation reproduction toxicity study had no adverse effects on reproductive parameters of the F0 parental animals and F1 pups of all groups (100, 300 and 1000 mg/kg bw/day) and did not induce any signs of developmental toxicity in the F1 pups.

Treatment-related systemic toxicity effects, however, were observed in the parental (F0) rats. These were considered as not adverse. For details, see the respective robust study summary and endpoint summary in IUCLID chapter 7.5.1.

The NOAELs (no observed adverse effect levels) for reproductive function of the F0 parental rats and F1 pups and for developmental toxicity of the F1 pups is considered to be >= 1000 mg/kg bw/day.

Short description of key information:
oral
1-generation study rat (GLP, OECD 415, BASF 1996)
NOAEL >1000mg/kg bw/day for reproductive function (F0 and F1) and developmental toxicity (F1)

Justification for classification or non-classification

No signs of of toxicity to reproduction or development were observed in the rat after oral dosage up to the limit concentration of 1000 mg/kg bw/d. Therefore, a classification is not warranted.