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Description of key information

See section carcinogenicity (chronic study of Kitahori et al. 1997).
The animals of the dosage groups showed dose-related toxic effects of the kidneys. No no-effect level was identified, but the clear decline of toxic effects beween the 2 dosages allows the estimation that a level of at least 13 mg/kg bw /day should be a no-effect level.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
13 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
One reliable study (Kitahori et al. 1997) with detailed documentation of results. Sufficient animal numbers. The study is valid with restrictions.

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

See section carcinogenicity (chronic study of Kitahori et al. 1997).

Rats were randomly divided into experimental groups, each consisting of 50 males and 50 females. Group I was given 0.5 % L-cysteine monohydrochloride (LCM), and group II 0.25 % LCM in their drinking water, while control group III was given tap water only for 108 weeks.

There were no statistically significant differences between treated and control rats in the results of the urine and serum analysis or hematological determinations or in the incidences of tumors.

With the body weights a significant dose-related decrease with the females were seen.

With regard to non-neoplastic lesions,

necrosis of the renal papillae was seen in 6 of 38 females rats in the 0.5% group, and 2 of 43 in the 0.25% group.

Hyperplasia of the kidney pelvis was seen in one female of each treated groups.

Calcification of the renal papillae was found in 2 female rats of the 0.5 % group.

Focal necrosis of the proximal tubules was found in 2 males and one female from the 0.5% dosage group.

Although no no-effect level was identified, the clear decline of toxic effects beween the 2 dosages allows the estimation that a level of at least 13 mg/kg bw/ day should be a no-effect level.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Repeated dose toxicity studies (28 or 90 days) do not need to be conducted because a carcinogenicity study with repeated dosing for 108 weeks was performed (Kitahori et al. 1997). This study is valid for the evaluation of the repeated dose toxicity because a dose related systemic toxicity was demonstrated. See iuclid section 7.7/ CSR section Carcinogenicity.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys

Justification for classification or non-classification

LOAEL (necrosis of the renal papillae) = 113 mg/kg b.w./ day and estimated NOAEL = 13 mg/kg bw..

There was no treatment related effect that would fullfill any criteria for classification and labelling according to the criteria laid out in

Regulation (EC) No.: 1272/2008 (especially annex I, section 3.8 and 3.9) and subsequent regulations. Also, according to the criteria specified by Directive 67/548/EEC and subsequent regulations, the substance L-Cysteine hydrochloride and its hydrate form are not classified.