Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

For 1,4 -diaminobutane exposure based waiving is jusitified because of low toxicological activity - only local irritation effects, no unusual findings in the other organs and tissues examined to suggest any systemic toxicity - and toxicokinetic data do not indicate systemic absorption via relevant routes of exposure, and there is no significant human exposure (since conditions at work are properly controlled and the half-life of 1,4 -diaminobutane in air is extremely short).

Furthermore, in a reprotox study with the read across substance Ethylenediamine dihydrochloride (EDA • 2HCl) no reproductive toxicity was observed .Some effects were observed in both sexes for the Fo and F1 parent rats. These effects were mainly associated with the high dosage level and included reduction of body weight gain and changes in liver (decrease) and kidney (increase) weights in the adult rats. The only microscopic lesion observed was hepatocellular pleomorphism in the high level F, adult males and females; a greater prevalence and severity of this lesion was seen in the female rats. The NOAEL of EDA.2HCl was reported to be 150 mg/kg/day (mating after 100 days of exposure).

The two-generation study with the other read across substance, hexamethylenediamine (HMD), showed also a NOAEL of 150 mg/kg/day. Fertility was not adversely affected by the dietary administration of HMD over two generations.

At birth pup body weights were not adversely affected by treatment but during lactation reduced weights were apparent in both sexes from the high dose group.

In addition, there were no treatment-related effects on testes weights and no effects were noted by macroscopic or microscopic examination of tissues evaluated

These results indicate that hexamethylenediamine does not have significant systemic target organ toxicity.


Short description of key information:
In the repeated dose inhalation study (28 days) nor in the drinking water study (2 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.
Two-generation studies with read across substances Ethylenediamine dihydrochloride (EDA • 2HC1) and Hexamethylenediamine (HMD) did not show any significant target organ toxicity. The same level of the NOAEL of 150 mg/kg/day was reported for both substances in these studies.
Parameters examined included indices of fertility, gestation of dams, gestation survival, 0- to 4-, 4- to 14- and 4- to 21-day survival of pups, number of pups born alive, and number of pups weaned per litter. Furthermore, observations were made on mortality, diet consumption, and body weight of the adult rats in Fo and F, generation. Randomly selected F, weanlings and adults and F2 weanlings were sacrificed and organ weights were obtained; in addition, gross and histologic examinations were conducted on these rats. No reproductive toxicity was observed in this study. Some effects were observed in both sexes for the Fo and F1 parent rats. These effects were mainly associated with the high dosage level and included reduction of body weight gain and changes in liver (decrease) and kidney (increase) weights in the adult rats. The only microscopic lesion observed was hepatocellular pleomorphism in the high level F, adult males and females; a greater prevalence and severity of this lesion was seen in the female rats.
NOAEL = 150 mg/kg/day (mating after 100 days of exposure)

Justification for classification or non-classification

No classification based on no indication of systemic toxicity in repeated dose tests with 1,4 -diaminobutane, or in two generation studies with the read across substances EDA and HMD.