N,N-dimethylacrylamide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

In a GLP compliant reproduction/developmental toxicity screening test according to OECD 421, N,N-dimethylacrylamide was given to rats by oral gavage (BASF SE 2013). Initially, groups of 10 male and 10 female Wistar rats (F0 animals) received the test substance, as a solution in (drinking) water, at dose levels of 5, 15 and 45 mg/kg bw/. Because all animals given 45 mg/kg/day lost weight during the first study week, the dose was reduced from 45 to 30 mg/kg bw/day from study day 7 onwards. Rats of the control group received the vehicle, water, alone. The duration of treatment covered a 2-week pre-mating and mating period for both sexes and the entire gestation period as well as 4 days of lactation in female animals followed by an additional treatment until one day before sacrifice (total length of treatment period: males 29 days, females 50 days). Accuracy, homogeneity and stability of formulations were demonstrated by analyses. The daily clinical observations revealed treatment-related signs of toxicity in all males and females at 45/30 mg/kg/day (poor general condition, closed eyelids, piloerection and reduced attention after dosing at the beginning of the pre-mating phase). Food consumption was significantly reduced at 45/30 mg/kg/day in males (pre-mating period) and females (premating period and first week of gestation). During the pre-mating period, growth was retarded in males at 45/30 mg/kg/day and, dose-dependently, in females at 15 and 45/30 mg/kg/day. Mean body weights of these animals remained lower compared to controls until the end of the study (mean terminal body weights were decreased by about 10%). The absolute weights of the testes and epididymides were not affected by treatment. Necropsy and histopathological examination (of the testes, epididymides and ovaries) revealed no treatment-related changes. Male and female mating and fertility indices, pre-coital time, duration of gestation, gestation index, post-implantation loss, litter size, live birth index, pup viability and sex ratio were not affected by treatment. Clinical observations and necropsy of pups revealed no substance-related changes either. Pup weights were decreased at 15 mg/kg bw/day (on PND 1 and 4) and above (PND 1). These lower pup weights were considered to be secondary to the reduced body weight of the dams in these groups. Under the conditions of this Reproduction/Developmental Toxicity Screening Test the oral administration by gavage of N,N-dimethylacrylamide to male and female Wistar rats revealed signs of systemic toxicity at dose levels of 15 mg/kg bw/day (reduced body weight) and above (reduced body weight and clinical signs). Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 5 mg/kg bw/day for male and female animals. The NOAEL for reproductive performance, fertility and developmental toxicity was 30 mg/kg bw/day.

Short description of key information:
In a GLP compliant, OECD 421, reproduction/developmental toxicity screening test in rats the highest dose tested, 30 mg/kg bw/day (by oral gavage), was a NOAEL for reproductive performance, fertility and developmental toxicity. The lowest dose tested, 5 mg/kg bw/day, was a NOAEL for general systemic toxicity in the parents.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Based on the available data, the test substance does not need to be classified for reproduction toxicity according to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Awaiting the developmental study according to OECD 414.