N,N-dimethylacrylamide

Endpoint summary

Additional information

Since no toxicokinetic studies are available for N,N-dimethylacrylamide the following assessment is based on the available physicochemical properties and results from toxicological studies.

 

The substance is a colorless to faint yellow liquid with a molecular weight of 99.13 g/mol. The calculated log Pow value is -0.13 at 25°C and the calculated solubility in water is 152 g/L at 25°C. Small water-soluble molecules (MW up to around 200) may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. Moderate log P values (between -1 and 4) are also favourable for absorption by passive diffusion. It is thus expected that the substance will be readily absorbed by the gastrointestinal tract. The mortality in the acute oral toxicity study and the systemic adverse effects observed in the available oral gavage combined reproduction/developmental toxicity screening test in rats (reduced body weight and clinical signs of poor health) indicate availability by the oral route.

Regarding respiratory absorption, moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The available acute inhalation toxicity study in rats provided no clear evidence of systemic availability. As signs of systemic toxicity occurred in the oral toxicity studies, which indicates the potential for absorption following ingestion, it is likely that the substance will also be absorbed if it is inhaled. Overall it is therefore expected that the substance will be readily absorbed by inhalation.

The low molecular weight of the substance (just below 100) would favour dermal uptake. However, as its water solubility is above 10,000 mg/L and the log P value below 0, the substance may be too hydrophilic to cross the lipid richt environment of the stratum corneum and, therefore dermal uptake would be low. Nevertheless, the signs of systemic toxicity observed in the available 13-week repeated dose dermal toxicity study in rats indicate that absorption has occurred.

As the log P value of the substance is lower than 3, it is unlikely to bioaccumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous. In the dermal repeated dose toxicity study alterations of clinical pathological parameters and minimal renal toxicity were observed, indicating distribution of the substance (and/or its metabolites).

In vitro studies showed that N,N-dimethylacrylamide is metabolized by mouse hepatic microsomal enzymes with a NADPH generating system as well as by hepatic glutathione S-transferases (Tanii, 1981). Both metabolic processes are enhanced by phenobarbital pretreatment. Following incubation with hepatic microsomes, N-methylacrylamide appeared to be a metabolite of N,N-dimethylacrylamide (as indicated by the gas chromatographic retention time and mass spectrum of the metabolite).

No specific statement can be made regarding the excretion route(s) of N,N-dimethylacrylamide. Its low molecular weight and good water solubility are favourable characteristics for urinary excretion.

 

Reference:

Tanii H. and Hashimoto K. (1981). Studies on in vitro metabolism of acrylamide and related compounds.