Tetramethylenediamine

Endpoint summary

Description of key information

Male and female rats were fed diets containing 0, 200, 2000 or 5000 ppm putrescine. Diets and tap-water were given ad libitum for a period of 5-6 weeks. Decreased body weights associated with diminished food intake were seen in the high dose group.
The no-observed-adverse-effect level (NOAEL) of Diaminobutate was 2000 ppm (180 mg/kg body weight/day)
In a 2 week drinking water study with Fischer 344 rats (doses 0.75 - 6.7 mg/l) with hexanediamine no toxic effects were found. Because there was no significant toxicity in these studies, the 13-week drinking water studies were not conducted.
In a 13 week  ad libitum feeding study with hexane diamine with Sprague-Dawley rats (0, 50, 150 and 500 mg/kg food per day),  no  abnormal reactions or treatment-related  deaths were observed throughout the study. No adverse gross or microscopic changes related to treatment were observed up to 500 mg HMD kg-1day-1.
In an inhalation study Sprague-Dawley rats were exposed to 1,4-diaminobutane for 4 weeks at dose levels up to 270 mg/m3. The only treatment related effect observed was a low grade irritation primarily in the anterior nasal cavity of high and intermediate dose group animals only. In conclusion, in the absence of any in vivo treatment-related changes and the lack of any organ or tissue changes to suggest systemic toxicity or local irritation, the low dose level of 11 mg/m3 is considered to be the no effect level. This NOEL is supported by 2 inhalation studies (13 weeks) with hexamethylenedinamine study in Sprague-Dawley rats, reporting NOEL's of 12.8 mg/m3 and 16 mg/m3.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

180 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

11 mg/m³

Study duration:

subacute

Species:

rat

Additional information

Oral exposure and skin contact are unlikely for 1,4 -diaminobutane. DAB is mostly used under strictly controlled conditions. In the repeated dose inhalation study (28 days), or in the feeding study (6 weeks) with 1,4 diaminobutane, no organ or tissue changes were reported to suggest any systemic toxicity. The inhalation NOEL is reported to be 11 mg/m3, based on irritation effects in the nasal cavities in the higher dose groups.

The drinking water studies with hexanediamine support these findings.

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: nose

Justification for classification or non-classification

No classification for repeated dose toxicity based on the subchronic inhalation and subacute feeding studies, no organ or tissue changes were reported to suggest any systemic toxicity.