Trisodium dihydrogen -N,N-[bis[2-[bis(carboxylatomethyl)amino]ethyl]]glycinate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

There are no reproductive fertility studies available for DTPA 3Na. In accordance with Annex VIII 8.7.1 Column 2, a screening reproductive toxicity/developmental study (OECD421) was considered unnecessary, since a pre-natal developmental toxicty study on DTPA 5Na is available.

 

 

 

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Using a read-across extrapolation approach from a GLP, OECD 414 guideline study on the structural analogue DTPA pentasodiuum salt, the maternal and developmental NOAELs of DTPA trisodium salt in rats are predicted to be 400 and 100 mg/kg bw/day or above (taking stoichiometric considerations into account). The two substances are structurally similar and have the same metal ion, chelating mode of action.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The source substance (DTPA 5Na) and the target substance (DTPA 3Na) are the pentasodium and trisodium salts of the same organic acid (Diethylenetriaminepentaacetic acid) and are therefore structurally very similar. The two substances have comparable high water solubility and would be rapidly and fully dissociated into common anions and cations in the gastro-intestinal tract. The absorption, distribution and metabolism of the two substances would therefore be expected to be essentially identical. The common organic acid moiety has a chelating mode of action and the trisodium salt would be expected to exert similar adverse developmental effects by the sequestration of essential metal ions.

Reason / purpose for cross-reference:

read-across source

Specific details on test material used for the study:

99% w/w

Species:

rat

Route of administration:

oral: gavage

Vehicle:

water

Duration of treatment / exposure:

day 6 through day 15 post coitum

Key result

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Basis for effect level:

other: teratology

Key result

Developmental effects observed:

yes

Lowest effective dose / conc.:

400 mg/kg bw/day (actual dose received)

Treatment related:

yes

Relation to maternal toxicity:

developmental effects occurring together with maternal toxicity effects, but not as a secondary non-specific consequence of maternal toxicity effects

Dose response relationship:

yes

Relevant for humans:

not specified

Conclusions:

The maternal and developmental rat oral NOAELs of DTPA trisodium salt are predicted to be 400 and 100 mg/kg bw/day or above, respectively.

Executive summary:

The maternal and developmental rat oral NOAELs of DTPA pentasodium salt are 400 and 100 mg/kg bw/day respectively (OECD 414). DTPA pentasodium salt is structurally similar to DTPA trisodium salt and the analogue has the same metal sequestering systemic mode of action as the target substance. Based on a read-across approach, and taking into account  stoichimetry, DTPA trisodium salt is predicted to have similarly or slightly higher oral NOAEL of circa 400 and 100 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Species:

rat

Quality of whole database:

(Category 1 (Relaible without restriction)

Justification for classification or non-classification

DTPA trisodium salt is considered to meet the CLP criteria for classification as 'reproductive toxicity: category 2.'