[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, calcium sodium salt

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

Additional information

In read across from a one generation reproductive toxicity study, the test substance was administered continuously via the diet to Long-Evans F0 generation females (20/group) at the onset of gestation and continued throughout the ensuing gestation and lactation periods. Dietary administration was continued to the F1 generation animals (10 males and 20 females /group) through a growth period and a mating, gestation and lactation period for two successive litters.

In the F0 generation, no treatment effects were evident in the low or mid dose groups. In the F1 generation, no treatment effects were observed in growth, food consumption, fertility-reproduction or litter examination parameters. At terminal sacrifice, mid dose males and high dose animals had lower body weights. In the mid and high dose levels, males had higher adrenal weights, both absolute and relative to body and brain ratios.

However in the absence of histopathological/clinical pathology examination results, it is not clear whether or not the weight change is a real effect.

In the absence of adverse clinical /reproductive effects for this substance, it is unlikely to be of toxicological significance.

Therefore the NOAEL for reproductive effects for F0 and F1 is > 3000 ppm.

Short description of key information:
In read across from a well conducted one generation reproductive toxicity study the test substance was administered continuously via the diet to Long-Evans F0 generation females (20/group) at the onset of gestation and continued throughout the ensuing gestation and lactation periods. Dietary administration was continued to the F1 generation animals (10 males and 20 females /group) through a growth period and a mating, gestation and lactation period for two successive litters. No treatment related effects on reproductive parameters were seen in any of the dosage groups. Therefore the NOAEL for reproductive effects for F0 and F1 is > 3000 ppm.

Effects on developmental toxicity

Description of key information

In read across from a  well conducted sudy, mated female Sprague Dawley rats were dosed by gavage at levels of 0.5g, 1g and 2g/kg (bw) of Dequest 2041 (neutral sodium salt) from gestation day 6 through to day 19 inclusive. Based on indications of maternal toxicity at 1 g/kg and 2 g/kg dose levels, the NOAEL for maternal toxicity is 2 g/kg  (bw) based on the active  acid. Because there were indications of maternal toxicity at the 2 g/kg  (bw) based on the active acid dose level any effects on post implantation loss or foetal weights were viewed as being secondary to maternal toxic effects.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Additional information

Mated female Sprague Dawley rats were dosed by gavage at levels of 0.5g, 1g and 2g/kg (bw) of Dequest 2041 (neutral sodium salt) from gestation day 6 through to day 19 inclusive. Based on indications of maternal toxicity at 1 g/kg and 2 g/kg dose levels, the NOAEL for maternal toxicity is 2 g/kg (bw).

Because there were indications of maternal toxicity at the 2 g/kg dose level, any effects on post implantation loss or foetal weights were viewed as being secondary to maternal toxic effects. No significant detectable embryonic or fetotoxic effects occurred at either the 0.5 g/kg or 1 g/kg dose levels.

It was also concluded that the skeletal malformations observed in the high dose group were secondary effects related to maternal toxicity. On the basis of the results, the NOAEL for developmental effects is > 2 g/ kg (bw) based on the active acid.

Justification for classification or non-classification

The available reproductive and developmental studies, all support the conclusion that EDTMP does not cause adverse effects on development. No classification for reproductive or developmental effects is required (Regulation 1272/2008 and 67/548/EEC).