1,7-Naphthalenedisulfonic acid, 2-[[4-chloro-6-(cyanoamino)-1,3,5-triazin-2-yl]amino]-5-hydroxy-6-[2-[2-methoxy-5-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]diazenyl]-, lithium sodium salt (1:?:?)

Endpoint summary

Description of key information

The NOAEL of the test substance was determined to be 250 mg/kg bw/day in the 28-day study in rats.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study was conducted to assess the subacute repeated dose toxicity of the test substance in rats according OECD guideline 407 and EU Method B.7.

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, 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 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 analyzed with the aid of a statistical program.

No deaths occurred throughout the study. Behavior, state of health, neurotoxicological, body weight gains and food consumption remained unaffected by the administration of the test substance in all dose groups.

Water consumption was distinctly increased in all animals of the high dose in the course of the treatment period. Consequently, the urine volume was increased in this group during the treatment period. Polyuria and polydipsia are well-known side effects for lithium. As the content of lithium is rather high in this test substance, these effects were most likely related to the lithium salt content.

The urine of most males of the 28-d treatment and the recovery high-dose groups was discolored salmon-pink in different intensities. Hematological and clinical chemistry investigations and organ weights did not exhibit treatment related adverse effects. The serum of almost all animals of the high-dose recovery and the intermediate and high dose final groups was discolored by the dye.

At necropsy of the final and/or recovery value animals of the intermediate and/or high dose groups showed reddish discolored Kidneys, skin, adipose tissue, testes, epididymes, stomach, and small intestines.

In conclusion, repeated administration of test substance caused reversible slight acute topical irritations in the submucosa of the stomach and pigment depositions in the kidneys of animals of the high dose group without causing any tissue damage. Additionally these animals showed sporadically temporarily increased salivation and distinctly increased water consumption, due to the lithium salt content. The test substance did not cause compound related adverse effects in the intermediate and low dose groups.

Under the test conditions, as a consequence of the combination of the effects in the high dose group the NOAEL is 250 mg/kg bw/day. (Dr. Seeberger A, 1999).

Justification for classification or non-classification

The NOAEL and NOEL of the test substance were determined to be 250 and 62.5 mg/kg bw/day respectively in the 28-d oral study in rats. However based on the results of the study, the test substance does not meet the requirement for classification according to according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).