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

Endpoint summary

Description of key information

NOAEL (repeated oral toxicity rat chronic study) = 250 mg/kg bw/day

Key value for chemical safety assessment

Toxic effect type:

concentration-driven

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The repeated dose toxicity of the substance via the oral route is evaluated using two in vivo chronic toxicity studies in combination to toxicity to reproduction, one performed on mice and one performed on rats.

In the chronic toxicity study performed on mice (EFSA, 2009), a NOAEL of 1500 mg/kg bw/day was reported for F1 mice as there were no significantly different effects compared to control animals.

In the chronic toxicity study performed on rats (EFSA, 2009), a NOAEL of 50 mg/kg bw/day was considered for F1 pups based on body weight and weight gain and on viability. 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.

Furtehrmore, the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1975) evaluated other studies on repeated dose toxicity of the substance:

- An oral feeding study in rats (5 per sex; 0, 125, 250, 500, 1000, 2500 mg/kg bw; duration of 90 days) showed no treatment-related effects on body weight, food intake, blood cell counts and organ weights (Hansen W.H. et al., 1960).

- A short-term (7 days) toxicity study on cats demonstrated no increase in Heinz bodies in the blood of cats after administered doses of 100 mg/kg bw (Oettel H. et al., 1965).

- A long-term study in dogs (groups of three male and three female) fed with diet containing 0.03 and 0.2 % of the test item for two years showed no colour induced effects in terms of body weight, food consumption, gross and microscopic pathology (Hazleton Labs Inc.a, 1967).

- A long-term study in rats (groups of 25 male and 25 female) orally fed with diets containing 0.0, 0.2 and 0.1 % of the test item for up to two years showed no colour induced in terms of body weight, food intake, survival, haematology, urinalyses, organ weights, gross and microscopic pathology (Hazleton Labs Inc.b, 1967).

- Another subchronic study in rats (20 per sex) reported by the Scientific Committee on Cosmetic Products and Non-Food Products (SCCNFP, 2004) showed no adverse effects on growth, behaviour, appearance, blood and urinary parameters after three months oral administration of 1500 mg/kw bw of the test item (Hazleton Labs Inc, 1965).

Moreover, it is important to highlight that the substance is included in the European Union Register of Feed Additives as per Regulation (EC) No. 1831/2003 and it is used to add colour to feeding-stuffs for non-food-producing animals. The substance is also authorised as a food additive in the European Union for use in foods in accordance with Regulation (EC) No 1333/2008. Also, as per Annex IV of Regulation EC No. 1223/2009, the substance is allowed as colorant in cosmetic products with Colour Index Number 47005 (with the purity criteria as set out in Commission Directive 95/45/EC (E104)). The low toxicity profile of the substance resulting from the two chronic studies used for the assessment of the repeated dose toxicity of the substance is, therefore, supported by the widespread use of the substance as feed and food additive as well as for the formulation of cosmetic products.

 

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

- Hansen W.H. et al. (1960). Sub-acute oral toxicity of ten D & C coal-tar colours. Sub-acute oral toxicity of ten D & C coal-tar colours,19, 390

- Hazleton Labs Inc, c. (1965). Unpublished report.

- Hazleton Labs Inc.a. (1967). Unpublished report.

- Hazleton Labs Inc.b. (1967). Unpublished report.

- JECFA. (1975). (Joint FAO/WHO Expert Committee on Food Additives), (1975). 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.

- Oettel H. et al. (1965). Die prüfung einiger synthetischer Farbstoffe auf ihre Eignung zur Lebensmittelfärbung. Arch Toxicol, 21:9-29.

- Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products.

- Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives.

- Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition (Text with EEA relevance).

- SCCNFP. (2004). Opinion of the scientific committee on cosmetic products and non-food products intended for consumers concerning Acid Yellow 3 - Colipa n° C54.

 

Justification for classification or non-classification

For the classification of the substance as STOT-RE, the dose in which significant toxic effects are observed is taken into consideration. Based on the available data obtained in the chronic toxicity study performed on rats (Biodynamics 1980 - EFSA, 2009), a LOAEL of 1000 mg/kg bw/day can be derived and 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. Criteria for classification of a substance as STO-RE Category 1 or Category 2 are reported in Annex I: 3.9.2.9.6 and Annex I: 3.9.2.9.7, respectively. Based on the results of the chronic toxicity study performed on rats (Biodynamics 1980 - EFSA, 2009) and considering the LOAEL of the substance, the substance shall not be classified as STOT-RE according to the CLP Regulation (EC) No. 1272/2008.