Registration Dossier

Diss Factsheets

Administrative data

Description of key information

No adverse effects were observed in a subacute oral (gavage) toxicity study in rats with the read across substance Analogue substance 1 at 1000 mg/kg/day (highest dose tested). The study predated GLP and OECD guidelines.

Key value for chemical safety assessment

Toxic effect type:

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
1 000 mg/kg bw/day
Study duration:

Additional information

Repeated dose toxicity:

The endpoint for repeated dose toxicity is based on a read across from an oral toxicity study performed with Analogue substance 1 (CIBA 1979). In a pre-GLP study male and female rats (Tif:RAlf, SPF; 20/sex/group) received the substance by oral gavage on 5 days a week over a period of 30 days (in total 22 doses). The treatment period was followed by a 2 -week recovery period. No effects were observed on food consumption, body weight, clinical signs, clinical laboratory examinations and pathology. Eye examination did not reveal any ocular changes. No loss of hearing ability was registered. It can be concluded from the observations made during this study that 1000 mg/kg/day of Analogue substance 1 produced no observable effects in male and female rats.

In support of this study a second read across study with Analogue substance 1 is available. This study (Leist, 1982), non-GLP, was performed according to ETAD Toxicological method No. 006. Determination of subacute oral toxicity to rats (28-days test). The results of subacute toxicity studies on eight selected colorants of low acute oral toxicity (LD50 > 2000 mg/kg) are reported. These eight colorants, selected from widely differing chemical structural types, were administered as 22 daily doses over a period of 30 days (no weekend dosing) at 1000 mg/kg body weight/day by gavage to female and male rats. Animals treated with the vehicle served only as controls. In most cases the treatment period was followed by a 15day recovery period. At the end of the treatment and the recovery period, hematology, blood chemistry and urinalysis measurements were carried out by standard methods on animals from control and test groups; each rat was also examined externally and by dissection for macroscopic abnormalities. At the end each rat was autopsied and selected organs, including liver, kidneys, adrenals and spleen were submitted for histopathological examination, following determination of the organ weights. Even at this high dose level all products were tolerated without irreversilble signs of toxicity. The survey of data available indicated that the substances investigated exhibited a very low cumulative toxicity.

Further support is given in the study of Dystar (non-GLP and not conducted according to any specific guideline). The toxicity of the dye Analogue substance 1 was examined in 3- and 6-month feeding studies with weanling albino rats. Groups of 10 males and 10 females each were fed the dye at dietary levels of 0, 375, 750, 1500 or 3000 ppm for 13 weeks and of 0, 750, 1500 or 3000 ppm for about 28 weeks. General condition, behaviour, survival, growth, food intake and food efficiency were not adversely affected in any of the groups. Haematological and blood biochemichal parameters did not indicate a treatment-related effect of the dye. The percentage of eosinophils was slightly increased at 3000 ppm in females only. There were no changes in the composition of the urine which could be attributed to the treatment with Analogue substance 1. Organ weights did not show distinct differences between the test groups and the controls. Gross pathology failed to reveal changes that could be attributed to the test substance. Microscopically, there were minimal liver changes, viz. pronounced lobular pattern of the liver in the 1500 and 3000 ppm groups in males of the 6- month study only. It was concluded that the no toxic effect level of analogue substance 1 when fed to rats for 6 months was 750 ppm in the diet, or 37.5 mg/kg body weight/day, with the understanding that the effects found at the 1500 and 3000 ppm levels were only weak, aspecific and of doubtful, if any biological significance.

Justification for classification or non-classification

Based on the findings of the repeated dose toxicity study with the read across substance Analogue substance 1, the test substance does not need to be classified according to the Directive 67/548/EEC and the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Categories Display