Reaction products of amines, dicoco alkyl and glycollic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

There is one key screening study for reproductive effects.

An OECD Guideline No. 421 study was conducted to generate limited information concerning the effects of the test article on male and female reproductive performance such as gonadal function, mating behaviour, conception, development of the conceptus, and parturition. Four treatment groups of twelve CD® [Crl:CD®(SD)] rats/sex/group were administered the test article at dose levels of 100, 300, 600, or 1000 mg/kg/day at dose volumes of 0.4, 1.2, 2.4, or 4.0 mL/kg, respectively. One additional group of twelve animals/sex served as the control and received the vehicle, peanut oil (arachis oil NF) at a dose volume of 4.0 mL/kg. The vehicle or test article was administered to all groups once daily via oral gavage. The males were dosed for 43 days, beginning 14 days prior to pairing. Dosing of the females began 14 days prior to pairing, through the mating period, up to and including Lactation Day (LD) 3.

Observations of the parental (P0) animals included clinical signs, body weights and body weight change, and food consumption during the premating/mating, gestation, and lactation periods, and parturition and litter data. Observations of the offspring (F1) included survival at birth and during lactation, individual pup body weights, and gross abnormalities. At study termination, necropsy examinations were performed on all P0 animals, and organs and tissues were collected, weighed and examined for select groups. On LD 4, surviving F1 pups were examined externally, euthanized, and discarded.

The analytical evaluation of the formulation samples confirmed that they were homogenous and at the targeted concentration required. Control samples were devoid of test article.

Oral administration of the test article to male and female rats at 100, 300, 600, and 1000 mg/kg/day in males during the premating/mating and postmating periods did not reveal any test article-related changes. This included parameters consisting of P0 clinical findings, body weight, body weight change, and food consumption. In addition, reproductive, fertility, parturition, and F1 litter data, including external pup observations, as well as P0 gross necropsy findings, organ weights, and microscopic findings did not reveal any changes that could be considered treatment related.

Based on the results obtained from this oral reproductive/developmental toxicity screening study in rats, a No-Observed-Adverse-Effect-Level (NOAEL) for general, reproductive, and developmental toxicity was considered to be 1000 mg/kg/day, the highest level tested and the limit dose designated by the guideline.

Short description of key information:
The No-Observed-Adverse-Effect-Level (NOAEL) for general, reproductive, and developmental toxicity was considered to be 1000 mg/kg/day, the highest level tested and the limit dose designated by the guideline

Effects on developmental toxicity

Description of key information

The No-Observed-Adverse-Effect-Level (NOAEL) for general, reproductive, and developmental toxicity was considered to be 1000 mg/kg/day, the highest level tested and the limit dose designated by the guideline

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

There is one key screening study for reproductive effects.

An OECD Guideline No. 421 study was conducted to generate limited information concerning the effects of the test article on male and female reproductive performance such as gonadal function, mating behaviour, conception, development of the conceptus, and parturition. Four treatment groups of twelve CD® [Crl:CD®(SD)] rats/sex/group were administered the test article at dose levels of 100, 300, 600, or 1000 mg/kg/day at dose volumes of 0.4, 1.2, 2.4, or 4.0 mL/kg, respectively. One additional group of twelve animals/sex served as the control and received the vehicle, peanut oil (arachis oil NF) at a dose volume of 4.0 mL/kg. The vehicle or test article was administered to all groups once daily via oral gavage. The males were dosed for 43 days, beginning 14 days prior to pairing. Dosing of the females began 14 days prior to pairing, through the mating period, up to and including Lactation Day (LD) 3.

Observations of the parental (P0) animals included clinical signs, body weights and body weight change, and food consumption during the premating/mating, gestation, and lactation periods, and parturition and litter data. Observations of the offspring (F1) included survival at birth and during lactation, individual pup body weights, and gross abnormalities. At study termination, necropsy examinations were performed on all P0 animals, and organs and tissues were collected, weighed and examined for select groups. On LD 4, surviving F1 pups were examined externally, euthanized, and discarded.

The analytical evaluation of the formulation samples confirmed that they were homogenous and at the targeted concentration required. Control samples were devoid of test article.

Oral administration of the test article to male and female rats at 100, 300, 600, and 1000 mg/kg/day in males during the premating/mating and postmating periods did not reveal any test article-related changes. This included parameters consisting of P0 clinical findings, body weight, body weight change, and food consumption. In addition, reproductive, fertility, parturition, and F1 litter data, including external pup observations, as well as P0 gross necropsy findings, organ weights, and microscopic findings did not reveal any changes that could be considered treatment related.

Based on the results obtained from this oral reproductive/developmental toxicity screening study in rats, a No-Observed-Adverse-Effect-Level (NOAEL) for general, reproductive, and developmental toxicity was considered to be 1000 mg/kg/day, the highest level tested and the limit dose designated by the guideline.

Justification for classification or non-classification

In accordance with CLP EC Regulation No. 1272/2008, the test material is not classified for reproductive toxicity in the absence of effects at the maximum dose concentration.