5',5'''-[ethylenebis(p-phenyleneazo)]bis[1',2'-dihydro-6'-hydroxy-4'-methyl-2'-oxo-1,3'-bipyridinium] dilactate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

NOAEL (fertility, rat) = 834 mg/kg bw/day

No impact on delivery or fertility parameters was observed, or changes in reproductive parameters of parental generation at any dose.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

834 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

good quality and reliability

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The test was run according to OECD guideline 422.

The test item did not influence the reproductive performance or the delivery parameters at any of the doses evaluated. A test item influence on the oestrous cycle was not found at any dose level. There were no toxicologically significant differences between the control and test item treated male or female animals in the examined parameters of reproductive performance or in the delivery parameters of dams. There were no test item related changes in parental organ weights (absolute and relative to body or brain weights) of brain, testes and epididymides of male animals at any dose level. No toxic or other test item-related lesions detectable by histological examination were found in the investigated reproductive organs (ovaries, uterus, vagina, testes, epididymides, prostate and seminal vesicles with coagulating gland) of male or female animals dosed up to 834 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

NOAEL (development, F1, rat) = 83 mg/kg bw/day, in presence of maternal toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

83 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

The test was run according to OECD guideline 422.

Development of F1 offspring was influenced by test item after repeated oral administration of dams from birth to post-natal day 13. An elevated level of thyroid stimulating hormone (TSH) was observed in offspring of all treatment groups along with slightly lower, though not dose related, concentration of FT4 at the two higher dose groups of 250 and 834 mg/kg bw/day on post-natal day 13. Higher extrauterine mortality (834 mg/kg bw/day), clinical signs with higher percentage (250 and 834 mg/kg bw/day), shorter anogenital distances (250 or 834 mg/kg bw/day) and reduced body weight development (250 or 834 mg/kg bw/day) were observed in offspring when compared to their relative controls. However, although several developmental parameters of offspring were altered, these changes might likely be a consequence of maternal toxicity, i.e. mainly due to lack or inadequate nursing by mothers or bad conditions of some dams at 250 and 834 mg/kg bw/day.

Justification for classification or non-classification

According to CLP Regulation (EC 1272/2008), reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.

For the purpose of classification for reproductive toxicity, substances may be allocated to one of two categories. Within each category, effects on sexual function and fertility, and on development, are considered separately.

-Category 1: known or presumed human reproductive toxicant. Substances are classified in category 1 for reproductive toxicity when they are known to have produced an adverse effect on sexual function and fertility, or on development in humans or when there is evidence from animal studies, possibly supplemented with other information, to provide a strong presumption that the substance has the capacity to interfere with reproduction in humans. The classification of a substance is further distinguished on the basis of whether the evidence for classification is primarily from human data (category 1A) or from animal data (category 1B).

-Category 2: suspected human reproductive toxicant. Substances are classified in category 2 for reproductive toxicity when there is some evidence from humans or experimental animals, possibly supplemented with other information, of an adverse effect on sexual function and fertility, or on development, and where the evidence is not sufficiently convincing to place the substance in category 1.

Based on available experimental data, effects seen in offspring could be associated to maternal toxicity, as mainly occurring in presence of inadequate nursing or bad conditions of dams. Such findings were evident in medium and high dose groups, where maternal toxicity becomes more significant.

Accordingly, classification of Basic Yellow 094 for developmental toxicity was found to be not applicable, as developmental effects of offspring were mainly associated to lack of maternal care and maternal toxicity.