Hexamethylenediamine

Endpoint summary

Description of key information

Oral: LD50 Combined (Males and females) = 1160 mg/kg.bw in rats (kr: 2, Directive 92/69/EEC, B.1)
Dermal: LD50 Combined (Males and females) = 1900 mg/kg.bw in rats (Kr: 2, Directive 92/69/EEC, B.3)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 160 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 900 mg/kg bw

Additional information

1- Acute toxicity by oral route:

A study was identified as the key study (Marzin, 1978) as it does satisfy the guideline requirement for an acute oral study (method B1 in the Directive 92/69/EEC) in the rat. Clinical signs were a decrease of the motor activity (at 1530 and 1170 mg/kg bw) and exessive salivation (either the tested doses). At necropsy, an ulceration of the pylore and all the surface of the gastric mucous membrane was noted. Oral LD50 combined = 1160 mg/kg bw.

The LD50 value for fasted male rats was equal to 792 mg/kg bw (Internal DuPont Co. Report, 1981) and the LD50 combined for rat = 980 mg/kg bw (HMD tested as powder, 10% in water ) (Anonymous, 1968) were considered as supporting data.

In all studies (cited above), HMD is considered as Harmful if swallowed.

2- Acute toxicity by inhalation:

No study is reliable for this end-point. However, the study is scientifically unjustified considering animal welfare as HMD was classified as corrosive. Moreover, it was also classified as irritating to the respiratory system based on results observed in sub-chronic studies conducted in animals (rats and mice) exposed by whole-body inhalation (NTP, 1993). Important local effects such as upper respiratory tract irritation were observed at concentrations lower than the classification concentrations limits (5 mg/L). The inhalation LCL0 is estimated at 750 mg/m3 in mice for a 10 minute exposure (DOSE Handbook, 1999).

3- Acute toxicity by dermal route:

A study was identified as the key study (Marzin, 1978) as it does satisfy the guideline requirement for an acute dermal study (method B3 in the Directive 92/69/EEC) in the rat. Clinical signs were a lower motor activity and closed eyes. Necrosis appeared on all the treated surface, without reversibility at time of death. Dermal LD50 combined = 1900 mg/kg bw.

The dermal LD50 female rabbit = 1100 mg/kg bw (Vernot, 1977) and was considered as supporting data.

In both studies, HMD is considered as Harmful in contact with skin.

Justification for classification or non-classification

- Hexamethylenediamine (Cas: 124 -09 -4) is classified in Acute Tox. Category 4 for the oral and dermal route (H302 and H312) in the Annex VI of the CLP regulation (1272/2008). By inhalation route, Hexamethylenediamine is not classified in the Annex VI of the CLP regulation (1272/2008).

- Based on the results of key studies, no changes of the HMD official classification is proposed for acute toxicity.