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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
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 substance (a structural analogue of Reactive Blue FC15353) was administered daily by gavage to Wistar rats at 0, 20, 150, or 500 mg/kg bw/day throughout the study period. The parental generation was allowed to give birth to one litter after successful mating.

In parental animals, there were no substance related deaths at any dose level. Blue discoloration of the organs was observed which was associated with the blue color of the test substance. Compared to controls, in high dose animals total bilirubin levels were decreased by 77% and 40% in males and females respectively. There was a dose dependent increase in cholesterol levels in females (reaching 59% in high dose females); whilst in males there was a general (but not fully dose dependent) increase in cholesterol over controls, with high dose males showing an increase of 31%.

In the parental generation males, the absolute and relative mean adrenal gland weights were statistically significantly increased in the low, medium and high dose groups (absolute by 39%, 23% and 36% respectively), (relative by 31%, 23% and 38% respectively). Absolute kidney weights were increased in high dose males and females by 18% and 17% respectively (which represented a 20% relative increase for both sexes). In low, medium and high dose males the absolute thymus weights was decreased compared to controls by 19%, 15% and 17% (25%, 13% and 15% relative to body weight). In females absolute thymus weights were only reduced in the high dose group (by 14%).

In the parental generation, the top dose, slight degeneration of the kidney cortex tubular was observed in all females, and moderate degeneration was observed in two males. In males only, very few to moderate numbers of basophilic (regenerating) tubuli were recorded in the renal cortex of four of five animals. From the extended toxicological investigation conducted on the satellite subgroup animals the repeat dose toxicity NOAEL is 150 mg/kg/day.

There were no substance related effects in body weight or food consumption in parental animals. There were also no treatment-related hematological changes. Additionally, male and female mating and fertility indices were not affected by treatment. Blue discoloration of the organs of parental animals were observed and was associated with the blue color of the test substance, however no other gross effects were observed.

High dose pup body weight gain on days 1-4 post-partum was reduced by up to 23% compared to controls such that mean body weights of these pups were statistically significantly reduced (10%) compared to controls on days 4 and 7 post-partum. During the last week of the lactation period (days 14-21 post-partum) body weight gain of high dose pups was similar to the control value, although mean body weight remained slightly (3%) below the control value at the end of the study.

There was no effect on offspring viability, including litter size or sex ratio, as well as no adverse clinical signs. There were no significant differences in the offspring development of animals treated with test material compared to controls. Additionally, differences between the groups concerning pup necropsy findings were considered spontaneous in nature and not associated with treatment.

Based on study results, the NOAEL for reproductive performance and fertility is 500 mg/kg bw/day for the parental generation rats. The NOAEL for general toxicity of the test substance is 150 mg/kg bw/day for parental animals. The NOAEL for developmental toxicity (growth and development of the offspring) was observed at 150 mg/kg bw/day for the F1 offspring. 


Short description of key information:
The test substance is considered to be without effect on parental reproduction up to 500 mg/kg bw/day. Additionally, the test substance is considered to be without effect on general toxicity in parental rats and developmental toxicity in offspring up to 150 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
One-generation GLP guideline study according to OECD 415; conducted with a structural analogue to Reactive Blue FC1535.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

No adverse effects on fertility have been reported in an extended one-generation study in rat according to OECD 415, conducted with a structural analogue to Reactive Blue FC1535.