4,4'-[1,2-ethenediylbis[(3-sulfo-4,1-phenylene)imino[6-[bis(2-hydroxyethyl)amino]-1,3,5-triazine-4,2-diyl]imino]]bisarenoate sodium salt

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

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

Reproduction toxicity

No data is available on reproduction toxicity for the test substance. However, reliable data from a 2 generation reproduction study performed with CAS 16470-24-9; a close structural analogue, is available.

 

A 2-generation rat study is available performed according to EPA Guideline OPPTS 870.3800 / OECD 416 under GLP conditions (ETAD, 2001). 26 Sprague-Dawley rats per sex per group were administered 100, 300 or 1000 mg/kg bw/day of the test substance (CAS 16470-24-9; 88.3% pure) by oral gavage. In parental animals, the only test substance-related effect noted was an increased kidney weight. In P animals, an increased kidney weight (absolute and relative to body and brain weight) was observed in females at 1000 mg/kg bw/day. In F1 parental animals, there was an increase in kidney weight in males (absolute and relative to body weight) and females (absolute and relative to body and brain weight) at 1000 mg/kg bw/day as well as an increase in kidney weight (relative to body weight) in females at 300 mg/kg bw/day. The statistical change in 300 mg/kg bw/day was considered to be spurious since no changes in absolute weight or kidney weight relative to brain weight were seen, and similar increases were not observed in 300 mg/kg bw/day males. None of the effects was related to histopathological changes; thus, the findings were not considered adverse. Furthermore, there were no test substance-related effects on reproductive performance noted for either parental generation. No adverse, test substance-related changes in growth or development of offspring were observed in either the F1 or the F2 generations. Based on the results of this study, the NOAEL for parental toxicity was 1000 mg/kg bw/day. For parental reproductive performance, the NOAEL was 1000 mg/kg bw/day. For offspring growth and development, the NOAEL was also 1000 mg/kg bw/day. This test yielded negative results indicating that the test substance has no potential for reproductive toxicity. Taken into account the small difference in molecular weight of the target and the source substance, the NOAELs are calculated to be 938 mg/kg bw/day.

Short description of key information:
- Reproduction toxicity:
Two generation study (OECD 416), rat, oral: NOAEL (reproduction) = 1000 mg/kg bw, NOAEL (parental) = 1000 mg/kg bw; RA from CAS 16470-24-9
Correction for molecular weight (target substance): 938 mg/kg bw/day (reproduction, parental)

Effects on developmental toxicity

Description of key information

Developmental toxicity/teratogenicity:
Prenatal developmental toxicity (OECD 414), rat, oral: NOAEL (developmental, maternal) = 1000 mg/kg bw; RA from CAS 16470-24-9
Correction for molecular weight (target substance): 938 mg/kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

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

Developmental toxicity

No data is available on developmental toxicity for the test substance. However, reliable data from a developmental toxicity study performed with CAS 16470-24-9; a close structural analogue, is available.

 

One study on developmental toxicity and teratogenicity according to OPPTS 870.3700 (equivalent to OECD TG 414) under GLP conditions have been performed in rats with CAS 16470-24-9 (no data on purity) (ETAD 1999). 30 pregnant Sprague-Dawley rats per group were dosed with 100, 400 or 1000 mg/kg bw/day by oral gavage on gestation days 6-19. The only substance-related effect observed was discoloured faeces at 400 and 1000 mg/kg bw/day. At skeletal examination of fetuses, the incidence of misaligned sternebra was slightly increased in all dose groups but was well within historical control range and not dose-related and therefore not considered to be test substance related. The incidence of rudimentary ribs was slightly above the historical control range at 100 and 1000 mg/kg bw/day. As the difference from the concurrent control group was not statistically significant and the increase was not dose-related, these findings were not considered biologically significant or test substance-related. The number of vertebral malformations at 1000 mg/kg bw/day (litter incidence 7.1 %) was slightly above the historical control range (0 - 7 %) and not statistically different from the vehicle controls. Therefore, this border finding too was considered to be within normal variation and unrelated to test substance administration. As there were no adverse maternal or developmental effects seen at any dose level, the NOAEL for both maternal and developmental toxicity is the highest dose tested (1000 mg/kg bw/day) (ETAD 1999).

Justification for classification or non-classification

The available data on reproduction toxicity is reliable and suitable for classification. Based on this data, classification for reproduction/developmental toxicity according to 67/584/EEC and EC/1272/2008 is not warranted.