1H-Indene-1,3(2H)-dione, 2-(2-quinolinyl)-, sulfonated, sodium salts

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL (offspring) = 50 mg/kg bw/day

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50 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

The reproductive toxicity of the substance is evaluated using two in vivo chronic toxicity studies, one performed on mice and one performed on rats.

- In the chronic toxicity study with reproductive phase performed on mice, no treatment-related effects were seen on fertility, pregnancy rate and numbers of live and dead pups. Growth rates and mortality rates showed no significant dose-related effects, other than a very slight increase in mortality in males at the highest dose level of 1500 mg/kg bw/day, of doubtful biological significance (EFSA, 2009).

- In the chronic toxicity study with reproductive phase performed on rats, no dose-related effects were noted on the number of pregnant females per group. The pups of the P0 dams were reported to display reduced viability and lower weight gains during lactation at dose levels of 0.5 % of the substance in the diet (equivalent to 250 mg/kg bw/day) and above, although no other treatment-related effects on reproductive parameters were noted. Based on these effects in the offspring of P0, EFSA Panel (EFSA 2009) derived a NOAEL of 50 mg/kg bw/day for this study. A NOAEL of 250 mg/kg bw/day was considered for F1 adult rats based on mortality, body weight and weight gain and on organ weights (EFSA 2009).

In another long-term study on reproductive and developmental toxicity reported by the Joint FAO/WHO Expert Committee on Food Additives (JECFAa, 1978), groups of rats received 0, 0.5, 5, 15, and 50 mg/kg bw/day substance in their diet through three successive generations. Offspring of the various matings were autopsied at weaning or selected for further breeding. No compound-related effects were observed with regard to parental mortality, body weight, food consumption, mating, pregnancy, fertility rates, numbers of embryos, corpora luteae, resorptions or necropsy findings.

  

EFSA. (2009). Scientific Opinion on the re-evaluation of Quinoline Yellow (E 104) as a food additive.

JECFAa. (1978). JECFA (Joint FAO/WHO Expert Committee on Food Additives). 22nd report. Summary of toxicological data of certain food additives and contaminants. WHO Food Additives Series, No. 13.

 

 

 

Effects on developmental toxicity

Description of key information

NOAEL (offspring) = 50 mg/kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

chronic

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

A NOAE fpr the offspring equal to 50 mg/kg bw/day is assigned based on the effects observed in the chronic study with reproductive phase on rats reported by EFSA Apnel (EFSA 2009). In this study there were no dose-related effects on the number of pregnant females per group. The pups of the P0 dams were reported to display reduced viability and lower weight gains during lactation at dose levels of 0.5 % of the substance in the diet (equivalent to 250 mg/kg bw/day) and above, although no other treatment-related effects on reproductive parameters were noted. Based on these effects in the offspring of P0, EFSA Panel (EFSA 2009) derived a NOAEL of 50 mg/kg bw/day for this study. A NOAEL of 250 mg/kg bw/day was considered for F1 adult rats based on mortality, body weight and weight gain and on organ weights (EFSA 2009).

The 1975 JECFA evaluation describes two studies on developmental toxicity of the substance (JECFAb, 1975):

- In a developmental toxicity in rats, groups of 20-24 pregnant females were administered doses of 0, 15, 50, or 150 mg/kg bw/day of the substance by gavage from gestational day 6 to 15. On day 20 foetus were sacrificed: no signs of foetal toxicity or anomalies were reported that could be attributed to administration of Quinoline Yellow.

- In a developmental toxicity study in rabbits, groups of 15 pregnant females received 0, 15, 50, or 150 mg/kg bw/day of Quinoline Yellow from gestation days 6 to 18. No significant maternal or foetal abnormalities were reported.

EFSA. (2009). Scientific Opinion on the re-evaluation of Quinoline Yellow (E 104) as a food additive.

JECFAb. (1975). ECFA (Joint FAO/WHO Expert Committee on Food Additives) 18th report. Toxicological evaluation of some food colours, enzymes, flavour enhancers, thickening agents, and certain other food additives. FAO Nutrition Meetings Report Series, No. 54A, 1975. WHO Food Additives Series, No. 6.

 

Justification for classification or non-classification

According to the CLP Regulation (EC) No. 1272/2008, the following categories for reproductive toxicants are available:

- 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 1A: Known human reproductive toxicant - The classification of a substance in this Category 1A is largely based on evidence from humans.

- Category 1B: Presumed human reproductive toxicant - The classification of a substance in this Category 1B is largely based on data from animal studies. Such data shall provide clear evidence of an adverse effect on sexual function and fertility or on development in the absence of other toxic effects, or if occurring together with other toxic effects the adverse effect on reproduction is considered not to be a secondary nonspecific consequence of other toxic effects. However, when there is mechanistic information that raises doubt about the relevance of the effect for humans, classification in Category 2 may be more appropriate.

- 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. If deficiencies in the study make the quality of evidence less convincing, Category 2 could be the more appropriate classification. Such effects shall have been observed in the absence of other toxic effects, or if occurring together with other toxic effects the adverse effect on reproduction is considered not to be a secondary non-specific consequence of the other toxic effects.

 

Effects on body weights and viability of the offspring were observed only for the pups of dams P0 in the chronic study in rats described by EFSA Panel (EFSA 2009), for which a NOEAL of 50 mg/kg bw/day was derived. In all the other available studies, no adverse effects on sexual function, fertility or on development were observed. Based on this, the substance is not classified as a reproductive toxicant.

EFSA. (2009). Scientific Opinion on the re-evaluation of Quinoline Yellow (E 104) as a food additive.