pentasodium 4-hydroxy-7-[(sulfonatomethyl)amino]-3-[(4-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)diazenyl]-8-[(2-sulfonato-4-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)diazenyl]naphthalene-2-sulfonate

Endpoint summary

Description of key information

A NOAEL of 1000 mg/kg bw/day was derived based on no treatment-related effects observed at any of the dose levels tested in the 28-d oral study in rats 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

A study was conducted to assess the sub acute repeated dose toxicity of the test substance in rats according EU Method B.7, OECD guideline 407, OPPTS 870.3050 and MITI Guidelines for screening toxicity testing of chemicals.

 

Groups of male and female rats received test substance by oral gavage at dose levels of 0, 62.5, 250 or 1000 mg/kg bw/day for a period of 28 d. On Day 29, 5 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 d.

Behavior and state of health were observed daily in all groups, Body weights and food consumption were recorded twice 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 and damage to the oral mucosa.

Neurotoxicological measurements including assessment of sensory function, motor activity, forelimb and hind limb grip strength were conducted at the end of the treatment period. Hematological examinations, clinical chemistry and urine analysis were carried out at the end of the treatment period and after the recovery period.

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 hind limb grip strength) were analysed with the aid of a statistical program.

 

No deaths occurred throughout the study. Body weight development, food consumption and general health status including Neurobehaviour were not affected by the administration of the test substance throughout the study in any groups.

Clinical pathology (hematology, clinical chemistry, and urinalysis) was not adversely affected by administration of the test substance in any group.

Organ weights were not affected by administration of the test substance in any group, and no compound-related changes were detected at necropsy or histopathology.

 

In conclusion, repeated administration of test substance did not cause any substance related changes at the doses administered. The NOAEL of the test substance was determined to be 1000 mg/kg bw/day in SD rats (Dr. Ehling G, 2002).

Justification for classification or non-classification

A NOAEL of 1000 mg/kg bw/day was derived based on no treatment-related effects observed at any of the dose levels tested in the 28-d oral study in rats and therefore does not meet the requirement for classification according to according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).