Sodium 3-[(1,5-dihydroxy-2-naphthyl)azo]-4-hydroxybenzenesulphonate

Endpoint summary

Description of key information

Repeated administration of Diamantechtrot BT for 28 days and a lifetime exposure to Allura Red did not cause any relevant compound-related adverse effects at any dose. The only effect seen, which could be related to a compound effect is the lowe terminal body weight in female rats dosed with 3604 mg/kg/day. With regard to the present studies, the No Observed Adverse Effect Level (NOAEL) for Mordant Black 9 is considered to be 1000 mg/kg body weight per day for sibacute or chronic exposure.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Additional information

Diamantechtrot

Groups of male and female rats received Diamantechtrot BT by oral gavage at dose levels of 0, 62.5, 250 or 1000 mg/kg body weight per day for a period of 28 days. On day 29 five males and five females from each group were killed and necropsied. Five males and five females from the control and high dose group were killed and necropsied after a recovery period of 14 days. Behavior and state of health were observed daily in all groups. Body weights and food consumption were recorded twice weekly, water consumption once weekly. Once before the first treatment and once a week thereafter detailed clinical observations were performed in all animals outside the home cage in a standard arena ('open field'). Additionally, the animals were examined for opacity of the refracting media of the eyes, damage to the oral mucosa, and impairment of dental growth. Neurotoxicological measurements including assessment of sensory function, motor activity, forelimb and hindlimb grip strength were conducted at the end of the treatment period. Hematological examinations and clinical chemistry were carried out at the end of the treatment period and after the recovery period. Urine analysis was performed at the end of the treatment and recovery period each. During necropsy the animals were examined for macroscopically visible abnormalities, the main organs were weighed and the organ to body weight ratios calculated. Organs and tissues were processed for histopathological examination and checked for microscopically visible changes. Body weights, hematological and clinical chemistry data, urine data (volume, specific weight), absolute and relative organ weights and neurotoxicological measurements (motor activity, forelimb and hindlimb grip strength) were analyzed with the aid of a statistical program to show differences compared to the controls.

No deaths occurred throughout the study. Behavior, state of health, body weight development, food and water consumption, organ weights, urinalysis as well as neurotoxicological, hematological and blood serum parameters remained unaffected by the administration of the test compound. After 28 days of treatment with Diamantechtrot BT male animals of the high-dose group showed orange discolored urine, which is due to the elimination of the test substance and/or its metabolites. Macroscopical and histopathological examination did not reveal any compoundrelated alteration.

In conclusion, repeated administration of Diamantechtrot BT did not cause any compound-related adverse effects at any dose. With regard to the present study, the No Observed Adverse Effect Level (NOAEL) is 1000 mg/kg body weight per day. Due to the orange discolored urine in male animals of the high-dose group after 28 days of treatment with Diamantechtrot BT the No Observed Effect Level (NOEL) is 250 mg/kg body weight per day.

Allura Red

FD & C Red No. 40 was fed to Charles River CD (Sprague-Dawley) rats as a dietary admixture in a lifetime toxicity/carcinogenicity study. The study included a phase during which the dye was administered to parental rats (30 of each sex per group) at concentrations of 0.0, 0.37, 1.39 and 5.19%, throughout the mating, gestation and lactation periods.

The concurrent control group received the basal diet. After random selection of the first-generation rats, the lifetime phase was initiated using the same dietary concentrations with 50 rats of each sex per group.

The maximum durations of exposure to the dye were 118 and 121 weeks for males and females, respectively. No compound-related adverse effects were observed, except for a reduction in body weight in high-dose females at the end of the study. The no-adverse-effect levels in this study were 5.19% (2829 mg/kg/day) for male rats, and 1.39% (901 mg/kg/day) for female rats.

Justification for classification or non-classification

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for reproductive toxicity is therefore required.