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EC number: 226-866-1 | CAS number: 5521-31-3
NOAEL 28d oral rat = 1000 mg/kg. No substance specific changes were observed.
NOAEL 90d oral rat = 50,000 ppm.
These data are based on read across approach to other category members.
GROUP MEAN HAEMATOLOGICAL VALUES AND STANDARD DEVIATIONS (S.D.) - FEMALES
* = significantly different from corresponding control group value p = 0.05
** = significantly different from corresponding control group value p = 0 .01
- = not applicable
No studies with repeated administration are available for the test substance. However, one 90-day and three 28-day studies are available for other category members (see attached category justification).
In the available 90-day oral repeated dose study performed with the read across substance from the same category (comparable to OECD guideline 408, but not fully compliant), Sprague-Dawley rats (15/sex/dose) were fed with the test substance at 10000 and 50000 ppm in the diet (Hoechst AG, 1967). A control group received normal diet without test compound. The following parameters were evaluated: clinical signs, body weight, food consumption, haematology, urinalysis, macroscopy and microscopy. The following organs were examined histologically: heart, lung, liver, kidney, adrenal glands, spleen, cerebrum, cerebellum, testes and ovaries, pancreas, pituitary, thyroid gland, stomach and small intestine. The general behavior in all animals of all dose groups was normal throughout the entire trial period and did not differ from that of the control animals. None of the experimental animals showed signs of a toxic effect. The pigment was excreted via the feces. The food consumption and the weight gains of the treated rats were normal and did not differ from that of the control rats. The haematological investigations revealed no pathological findings. Investigation of the urine showed no pathological findings which could be attributed to the pigment administered. Macroscopic and microscopic examination revealed no pathological organ damage. A NOAEL of 50000 ppm for male and female rats was observed for the test article.
In a 28-day oral toxicity study with a second structural analogue (read-across) according to OECD guideline 407 and under GLP, Sprague-Dawley rats (5/sex/dose) were administered the test substance at 750, 3750 and 15000 ppm in the diet (Safepharm Laboratories Ltd, 1990). These concentrations in the diet are equal to 79, 404 and 1573 mg/kg bw/day for males and 78, 380 and 1501 mg/kg bw/day for females. The following parameters were evaluated: clinical signs, body weight, food efficiency, water consumption and compound intake, haematology, blood chemistry, urinalysis, organ weights and histopathology. None of the animals died during the study. No clinically observable signs of toxicity were noted in test or control animals throughout the study. Bodyweight gain in all test animals was comparable with that seen in controls. There were no treatment-related changes in food consumption and food efficiency during the study. Anaemia was demonstrated in females treated with 15000 ppm, but not in males from the same dose group, identified by statistically significant reductions in haemoglobin levels, erythrocyte counts and haemotrocrit. The anaemia was very slight and apparently completely reversible since no such changes were seen in satellite high dose females after fourteen days without treatment. No toxicologically relevant changes were detected in any of the urine parameters measured. No treatment-related differences in organ weight were detected between test and control animals. All morphological changes were those commonly observed in laboratory maintained rats of the age and strain employed and, since there were no differences in incidence or severity between control and treatment groups, all were considered to be without toxicological significance.In conclusion,a NOEL of 3750 ppm / 380 mg/kg bw/day for females was established based on slight anaemia which was completely reversible. The NOAEL was therefore set at the highest dose level, i.e., at 15000 ppm / 1573 mg/kg and 15000 ppm / 1501 mg/kg bw/day for male and female rats, respectively.
Two more 28-day studies are available for two additional substances from the same category (Notox, 2006 and RTC, 2006). Both studies were compliant with GLP and OECD guideline 407. In both studies, the test article was administered to groups of 5 rats per sex and group at dose levels of 100, 300 and 1000 mg/kg bw. Control animals were treated with the vehicle alone. Five additional animals for each sex were included in the high and control groups for recovery assessment over a period of two consecutive weeks. The following parameters were evaluated: clinical signs daily, functional observation tests, body weight and food consumption weekly, clinical pathology at the end of treatment, macroscopy at termination, organ weights and histopathology on a selection of tissues. No toxicologically relevant changes were observed in any of the parameters determined in these studies. Consequently, a NOAEL of 1000 mg/kg body weight was established for both tested chemicals.
Conclusion: No data from repeated dose studies with the test article are available. But according to the category approach, the data available for other category members is used to assess the toxicity of the test article. Based on the available and reliable data obtained in long term application studies with four category members, no classification for repeated dose toxicity is warranted. The established NOAELs for the tested substances were all above 1000 mg/kg. Therefore, a NOAEL of 1000 mg/kg bod weight was also established for the test article based on this read across/category approach.
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for repeated dose toxicity is not warranted under Regulation (EC) No.1272/2008.
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