Ethyl 3,5-dichloro-4-hexadecyloxycarbonyloxybenzoate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproduction/Developmental Screening study (OECD 421), rat: NOAEL (reproduction) >750 mg/kg bw/day in parental animals. NOAEL systemic toxicity (P, F1) > 750 mg/kg bw/day (males/females)

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

750 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a reproduction/developmental toxicity screening test performed according to OECD 421, the potential adverse effect of ethyl 3,5-dichloro-4- hexadecyloxycarbonyloxybenzoate (AF-366) on reproduction and developmental parameters in rats was assessed (Flaškárová, 2011).

12 Wistar rats/sex/dose were administered 30, 150 and 750 mg/kg bw/day of the test substance; males for 28 days during the pre-mating and mating periods, and females for up to 56 days during the pre-mating, mating, and gestation period and during lactation until day 4. There were 5 unscheduled cases of mortality in female dose groups; 1/12, 2/12 and 2/12 in the 30, 150 and 750 mg/kg bw/day groups, respectively. The causes of these deaths were not test substance-related. There were no treatment-related clinical signs. In the female mid- and high-dose groups, food consumption was reduced during week 2 of the gestation period. This effect is considered to be incidental as the intake was comparable to the control group the rest of the study period. No treatment-related findings were noted during gross necropsy and histopathological examination. In this study the NOAEL for systemic toxicity is considered to be ≥ 750 mg/kg bw/day for male and female rats, as no effects were noted up to and including the highest dose level.

There was no statistically significant difference in reproductive parameters (measured as fertility rate and gestation index) between the control group and treatment groups. Therefore, the NOAEL for reproduction in males and females is considered to be ≥ 750 mg/kg bw/day, as no effects were observed up to and including the highest dose level.

There were no substance-related effects on offspring viability (measured as live birth index and survival index). No clinical signs of toxicity were observed in the offspring and there were no effects on the body weight. No treatment-related effects were observed up to and including the highest dose level, therefore the NOAEL for developmental effects is considered to be ≥ 750 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

Reproduction/developmental toxicity screening test (OECD 421), rat, gavage: NOAEL developmental (F1) > 750 mg/kg bw/d (males/females), NOAEL (maternal) >750 mg/kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

750 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In a reproduction/developmental toxicity screening study performed according to OECD 421, the potential adverse effect of ethyl 3,5-dichloro-4- hexadecyloxycarbonyloxybenzoate (AF-366) on reproduction and developmental parameters in rats was assessed (Flaškárová, 2011). The offspring was observed for viability and treatment-realated effects until Day 5 postpartum.

There was no statistically significant difference between the control and treatment groups for the live birth index, viability index, number of pups and sex ratio of the pups. No clinical signs of toxicity were observed in the offspring and there were no effects on the body weight. No treatment-related effects were observed up to and including the highest dose level, therefore the NOAEL for developmental effects is considered to be ≥ 750 mg/kg bw/day.

Justification for classification or non-classification

The available data on fertility, reproduction and development do not allow a robust hazard assessment with sufficient confidence for classification according to Regulation (EC) 1272/2008, and therefore, no statement on classification can be made.