3-dimethylaminopropiononitrile

Endpoint summary

Description of key information

3-dimethylaminopropionitrile cause urinary bladder And kidney damage after ingestion

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

350 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

100 mg/m³

Additional information

There are limited oral and inhalative data available to assess the toxic potential of 3-dimethylaminopropionitrile after repeated dosing.

Oral

In a subacute study with male Sprague-Dawley rats, five animals received 350 mg/kg bw for 14 days (Mumtaz et al.1991).

Animal weight, water consumption, and urine volume were recorded every 24 h . Morphologic and histologic studies on liver, bladder, and kidney were performed at the end of the 2-wk period. However relevant study parameters (i.e. hematology, clinical chemistry, histology) and a post exposure period are missing. Results of morphologicand histologic studies were not reported. Bladder lesions were found and reported in cocurrent 3 days sudies including same concetrations. A decrease in animal weight, water consumption, and urine volume lead to a LOAEL of 350 mg/kg bw, a NOAEL was not identifiable. In a shortly described study with limited reliability, rats were treated twice on one day with 0.31 or 0.62 mL/kg bw, corresponding to ca. 267 or 533 mg/kg bw (density 0.86 g/mL), and sacrificed after three days (Jaeger et al. 1980, Val. 4). At both doses acute macroscopic and histological changes (urinary bladder) occured. The changes consisted of massive transmural edema, acute ulcers and inflammation and occasionally hemorrhagic necrosis of the bladder wall.

Inhalation

A 14-day screening study with rats was conducted with the objective to detect neuropathological changes; due to missing test parameters no AEC was identifiable in this study (BG Chemie 1989). Groups of 5 Wistar rats per sex were exposed to 0 ; 0.01 ; 0.1 and 1 mg/L, respectively, for 6 hours per workday for two weeks before sacrifice. Mortality, clinical signs, body weight, urinalysis, gross necropsy and histology were studied and therefore some relevant study parameters (i.e. hematology, clinical chemistry) and a post exposure period are missing. At the highest concentration of 1 mg/L toxic effects (unspecific clinical signs, retarded body weight gain) were observed. However, neither urine parameters nor pathological/ histopathological examinations showed a significant substance-related effect. The NOEC is carefully considered to be 0.1 mg/L.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys; urogenital: urinary bladder

Justification for classification or non-classification

According to the available information, there is a need to classify 3-dimethylaminopropionitrile for its toxic potential after repeated dosing.

Based on CLP, a classification & labelling with STOT RE Cat. 2 (GHS) appears justified and is therefore applied for DMAPN CAS No. 1738 -25 -6.

 

The underlying reason is that based on CLP (3.9.2.6) there is Human evidence available, however effects levels cannot be quantified and the effect is at least partly reversible according to the literature reviewed and as assessed by the German MAK commission (2003). A comparable exposure situation is not to be expected und e the conditions the substance is being handled at the workplace today, in addition.

More important, and justifying the CLP-exemption for classification & labelling as STOT RE Cat. 2 instead of Cat. 1 (based on Human evidence), the effects levels observed in animal studies are outside the guidance values for classification & labelling. In the available 14 day studies, no effects have been observed on bladder function at the high dose = 1 mg/l/6h/day. With respect to oral exposure, this is comparable to doses where effects on bladder function etc. have been reported.