N,N-dimethylpyridin-4-amine

Endpoint summary

Description of key information

The acute oral LD50 in rats is 140 mg/kg bw, and the acute dermal LD50 in rabbits is 90 mg/kg bw.  The acute inhalation LC50 of a structural analogue substance (4-AP) is 0.53 mg/L (0.00053 mg/m3).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

140 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

0.001 mg/m³ air

Quality of whole database:

adequate

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

90 mg/kg bw

Quality of whole database:

adequate

Additional information

The acute oral LD50 for DMAP in rats is 140 mg/kg bw in the key in vivo study, and is supported by several non-GLP studies in which the LD50 in rats is between 100 and 500 mg/kg bw.

The acute dermal LD50 in rabbits is 90 mg/kg bw in the key study, and is generally supported by additional non-GLP studies in rabbits and guinea pigs in which the LD50 is in the range of 50 to 200 mg/kg bw.

A skin corrosion study in rabbits is also informative, in that all 6 rabbits died within 4 hours after occlusive dermal exposure (of intact and abraded skin) to 167 to 250 mg/kg bw DMAP. However, the acute dermal toxicity/corrosion protocols employed are more aggressive than those of current guidelines, in that the skin of half the animals was abraded which enhances absorption.

The acute inhalation LC50 of a structural analogue substance (4-AP) is 0.53 mg/L (0.00053 mg/m3).

Justification for selection of acute toxicity – oral endpoint
Guideline study under GLP

Justification for selection of acute toxicity – inhalation endpoint
experimental study of structural analogue

Justification for selection of acute toxicity – dermal endpoint
Guideline study under GLP

Justification for classification or non-classification

According to Regulation EC. No. 1272/2008, the substance is classified as Category 3 for Acute Oral Toxicity, as the LD50 in rats is 140 mg/kg bw. This falls in the range of 50 to 300 mg/kg bw for Category 3.

The substance is classified as Category 2 for Acute Dermal Toxicity, as the key LD50 value in rabbits is 90 mg/kg bw. This falls in the range of 50 to 200 mg/kg bw for Category 2.

The substance is classified as Category 3 for Acute Inhalation Toxicity, as the LC50 of a structural analogue substance (4-AP) is 0.53 mg/L. This falls in the range of 0.5 to 1.0 mg/L for Category 3.

DMAP is classified for specific target organ toxicity (neurotoxicity), single exposure (STOT-SE), based on its activity as a potassium channel blocker in neurons. Frequent findings of DMAP (and 4AP) exposure in mammals and birds are tremors, convulsions, and death. This neurotoxicity effect is not addressed by any other hazard classification. It qualifies as Category 1, based on the existence of “reliable, good quality” human data (on 4AP) suggesting that functional disturbances can be “significant and/or severe” (ECHA, 2015).