Diammonio(ethyl)[4-[[4-[ethyl(3-sulphonatobenzyl)amino]phenyl](2-sulphonatophenyl)methylene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL reproductive toxicity (male rats) = 1072 mg/ kg bw/day

NOAEL reproductive toxicity (female rats) = 1319 mg/ kg bw/day

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 072 mg/kg bw/day

Study duration:

subchronic

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 following reported data were obtained for Similar Substance 1. It is expected that the Target substance will present similar effects of reproductive toxicity. Justification for Read Across is given in Section 13 of IUCLID.

The publication by Borzelleca (Borzelleca, 1990) describes a life-time exposure dietary study that starts with in-utero exposure of the F1 generation of Similar Substance 1. For this purpose, F0 rats (60 per sex and dose) were treated for two months prior to mating with doses of 0.5, 1 and 2 % in the diet, treatment was continued during gestation. The F1 generation was weaned onto the same diet as the F0 generation and kept until the interim sacrifice after 12 months (10 animals per sex and dose), until their natural death or scheduled sacrifice after 30 months. The F1 generation consisted in total of 70 animals per sex and dose group, with at least each one male and female from each litter. The study was performed to support the safe use as a food colorant and used test material of 90% purity certified by the US FDA. The design is comparable to that of the basic extended one-generation study (OECD 443), but the F1 generation is kept until their natural death to assess the carcinogenic potential.

The publication gives little details on the reproductive part of the F0 generation; it states that no adverse effects were noted on fertility, gestation, parturition, lactation, the number of live born pups, the number of stillborn pups and the survival until weaning. From the F1 generation, at least one animal per litter was used for the chronic study with an interim sacrifice after 12 months. Histopathology of the gonads of the F1 generation showed no adverse effects. F1 animals showed normal body weight development until week 102. After that, females of the high dose group showed lower body weight gains and their final survival rate was reduced. Considering the occurrence at the very high dose after the very long exposure, this is not considered to be related to in-utero or pup exposure.

In EFSA Expert Panel (EFSA, 2010) the study from Borzelleca has also been reported in the reproductive toxicity evaluation for Similar Substance 1. The Panel furtherly concluded that the NOAEL for this study is 1318 mg/kg bw/day for females, and 1073 mg/kg bw/day for males.

In conclusion, there is no indication that the substance affects fertility of rats neither from the functional data nor from histopathology data.

References:

- Borzelleca, J.F. et al. 1990.Lifetime Toxicity/Carcinogenicity Studies of FD&C Blue no. 1 (Brilliant Blue FCF) in Rats and Mice.Fd. Chem. Toxicol.28, 221-234.

- EFSA 2010. Scientific Opinion on the re-evaluation of Brilliant Blue FCF (E 133) as a food additive1, EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS).

Effects on developmental toxicity

Description of key information

NOAEL developmental toxicity = 630 mg/ kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

630 mg/kg bw/day

Study duration:

subacute

Species:

other: rat and rabbit

Quality of whole database:

Only abstract information of study reports owned by the CTFA is availble.

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 following reported data were obtained for Similar Substance 1. It is expected that the Target substance will present similar effects of developmental toxicity. Justification for Read Across is given in Section 13 of IUCLID.

Information on a teratogenicity study in rats and rabbits has been published in form of a short abstract by the Inter-Industry Color Committee Task Force, Cosmetic, Toiletry and Fragrance Association, Inc. (CTFA), Washington, D.C. According to this abstract, the studies were performed at commercial CROs. From the reference to the two-year feeding study in rats, the highest tested dose level was 630 mg/kg bw and given by gavage. No adverse effects on skeletal or soft tissue were observed. The authors of this publication have published high quality data in other journals. It is assumed that the teratogenicity study described here in a very brief form is of high quality.

References:

- Burnett, C.M et al. 1974. Teratogenic Study with Certified Colors in Rats and Rabbits.Toxicol. Appl. Pharmacol.29: 121.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, adverse effects on development of the offspring and adverse effects on or via lactation.

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.

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.

Since no effects on sexual function and fertility or on development have been generated by the test substance, no classification is deemed for reproductive and developmental toxicity.