Di(µ-2,2´,2´´-nitrilotris(ethanol)-diperchlorato)dinatrium

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL (P/F1, reproductive) = 30 mg/kg-day (nominal)

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No data are available for the assessment of the toxicity potential of the substance on fertility. Available data from literature for the dissociation substances are used for the assessement of the toxicity of the substance. Justification for Read Across is given in Section 13 of IUCLID.

Effects on developmental toxicity

Description of key information

NOAEL (rats) = 30 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No data are available for the assessment of the toxicity potential of the substance on development. Available data from literature for the dissociation substances are used for the assessement of the toxicity of the substance. Justification for Read Across is given in Section 13 of IUCLID.

Justification for classification or non-classification

For the assessment of classification for reproductive toxicity of the substance, data on the dissociation substances were evalauted.

Exposure to perchlorate up to 30 mg/kg bw/day (maximum concentration tested) did not produce any reproductive effects to P1 and F1 generation rats. In the two-generation study, effects on lactation could be evaluated; it is noticable that the lactation index in the exposure groups (0.001 - 30.0 mg/kg bw-day) was comparable to the one of control group. Furthermore, viability index and litter size were not affected by perchlorate exposure while pup weights were even increased in some cases. Triethanolamine did not produce any reproductive or developmental effects up to the tested concentration (1125 mg/kg bw/day) as assessed in a post-natal mouse screening test and does not cause any developmental effects according to a developmental toxicity study (rats and rabbits, dermal) and a pre-, per- and postnatal study (rats, oral).

Perchlorate did not induce any developmental effects to fetus when administered in pregnant rabbits at doses as high as 100 mg/kg/day in the drinking water. No fetal alterations, either malformations or variations, were attributable to the perchlorate administration in rats. However, the average number of ossification sites per litter for sternal centers and for forelimb phalanges were significantly reduced in the 30.0 mg/kg-day exposure group, these reductions were considered reversible developmental delays and were not considered teratologically important because there were no skeletal malformations of the sternum or phalanges at this exposure level. However, based on these findings the NOAEL for developmental toxicity was found to be 1.0 mg/kg bw/day based on developmental delays in ossification which occurred in the 30.0 mg/kg-day group. Notwithstanding the effects of the substance on the number of ossification sites, it is worth saying that no adverse effects on development occured at levels that did not cause maternal toxicity. It could be suggested that these adverse effects were influenced by the maternal toxicity which was noted in even lower doses.

Based on the data of perchlorate and triethanolamine, the substance is not classified for reproductive toxicity. This is in accordance with eMSCA conclusion for the toxicity to reproduction (fertility and developmental) of triethanolamine, as stated in the Substance Evaluation Report- CoRAP (version 1.1, dated August 2015) and with eMSCA conclusion for reproductive toxicity of perchlorate as stated in the Substance Evaluation Conclusion Document- CoRAP (dated August 10th 2016).