3-dimethylaminopropiononitrile

Neurotoxicity

Description of key information

A 14-day screening study was performed with male and female Wistar rats to detect neuropathological changes (BG Chemie 1989). No neurological change was found at the highest concentration tested(NOAEL 1 mg/L) . No neurotoxic changes were found in workers were exposed to DMAPN for a mean exposure of more than 9 years to maximum air concentrations of 0.007 to 0.024 ppm (Deckert et al. 1982). There may be neurotoxic effects at in humans at higher concentrations.  However, these effects were seen at mixed exposure (ESN NIAX Katalysator in Polyurethan production) with other substance and therfore not clearly attributable to dimethylpropioaminonitril.

Key value for chemical safety assessment

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

NOAEC

1 000 mg/m³

Additional information

Neuropathy

A 14-day screening study was performed with male and female Wistar rats to detect neuropathological changes (BG Chemie 1989). Five animals per sex and dose were exposed to 0; 0.01; 0.1 and 1 mg/L 6 hours per workday, respectively. There were no substance-related neuropathological changes found after histological examination; the NOAEL is therefore 1 mg/L.

In long term studies with rats running 2 to 9 months, exposure to 450 mg/kg bw in drinking water caused enlarged distal motor and spindle axons with disordered neurofilaments (detected) by electron microscopy); enlarged motor nerve terminals were observed (Keogh 1983).

Neurobehaviour

In another subacute study, 3 -dimethylaminopropionitrile was administered i.p. to male Sprague-Dawley rats for two weeks (Gad et al. 1979). The dose ranged from 0.01 to 1 mL per kg bw (corresponding to ca. 8.6 mg to 860 mg/kg bw) and the post-exposure period was one week; neurobehavioural Irwin screen tests were performed on days 1, 5, 8 and 12 of dosing and on day 7 after dosing. A comparable test with mice was performed treating with 0.25 to 1 ml/kg bw (= ca. 215 - 860 mg/kg bw). Both rats and mice of the 430 and 860 mg/kg bw groups died within a few minutes after dosing. Incidence of convulsions, tremor and a loss of micturation response, leg crossing (tonic contracture of hind limbs) were observed in rats treated with 8.6 to 215 mg DMAPN/kg bw in a dose-dependend manner, while mice receiving 215 mg DMAPN/kg bw showed convulsions and tremors. No histological changes were found in surviving rats and mice, respectively. All signs were completely reversible in rats and mice during dosing or at least within the post-exposure period; therefore these effects are considered as adaptive and/or reversible and, finally, not adverse. The NOAEL is 215 mg/kg bw (based on mortality in higher doses) and the LOEL is 8.6 mg/kg bw (based on reversible effects).

In the above described 14 -day screening study via the inhalation route, neurobehavioural effects (reduced startle response) were slight and not described in sufficient detail to identify a respective NOAEL (BG Chemie 1989).

Human data

Human data: In 1978, beside sexual dysfunction symptoms also neurologic effects were observed in workers in two plants processing ESN-NIAX katalysator in Polyorethanproduction (95% DMPAN) in the USA (Keogh 1983). Urinary retention, urinary pain, insomnia, irritability, muscle weakness, paresthesias, were found to be mainly promptly reversible symptoms. However, after two years still symptoms in the bladder and the PNS were observed.

In contrast, no neurotoxic changes were found in an examination of a German plant processing DMAPN (Deckert et al. 1982). 34 examined workers were exposed to DMAPN for a mean exposure of more than 9 years to maximum air concentrations of 0.007 to 0.024 ppm during the study; the former exposure levels are, however, considered higher.