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Diss Factsheets

Toxicological information


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Administrative data

Description of key information

The effects found in the study are not relevant as different depletion diets are examined. A 14 to 17 months cystine depletion diet in mice results      even in high protein diets in pathologic calcification, primarily in the lungs but also in the aorta and arteries of other organs sectioned. 
The effect of a L-Cystine overdose is not examined and not not discussed.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

For L-Cysteine and the read-across substance L-Cystine no experimental study on cancerogenicity is available. There is no indication from the existing studies on CMR- toxicity that L-Cystine has toxicity referring to CMR endpoints. L-Cystine is a natural occurring amino acid present in all living cells. L-Cystine (and L-Cysteine, respectively) is an amino acid that is required for normal functioning of humans. There is sufficient weight of evidence for the absence of reprotoxic effects. There is no indication that the substance is able to induce hyperplasia or pre-neoplastic lesions in subchronic studies. Extensive genotoxicity testing does not raise any concerns for further studies. Additionally L-Cystine (and L-Cysteine respectively) are natural amino acids. It can be stated that amino acids are generally quickly absorbed and utilised in the mammal metabolism and that the amounts used in studies are generally far below the daily intake of an adult European individual (EFSA): as discussed in section 5.1.3. the intake of 2.2 g L-Cysteine which corresponds to approximately 1.1 g L-Cystine is a realistic value for daily intake. Both substances are linked by metabolic pathways and via chemical oxidation. A significant amount of L-Cystine (and L-Cysteine, respectively) is usually taken up via the food.

In usual diet, most amino acids are supplied as constituents of protein and not as free amino acid. Protein intake clearly modifies plasma amino acid levels. However, amino acid concentrations are subject to homeostasis and the plasma concentrations vary within fixed limits and are tightly regulated. Exposure with L-Cystine (and L-Cysteine, respectively) from uses which are covered by this registration would only marginally increase the total daily L-cystine dose (and L-Cysteine dose, respectively) which is taken up via the food. Even if the plasma amino acid concentration would increase/vary by any use such fluctuations are physiological and subject to homeostasis. Therefore it is highly unlikely that L-Cystine (and L-Cysteine, respectively) taken up via any use covered by this registration would result in systemic effects. A repeated dose toxicity studies consistently indicated the very low toxicity of L-Cystine (and L-Cysteine, respectively). Even in very high doses no toxicity is observed and no adverse effects were reported for the reproductive organs. Moreover, L-Cystine (and L-Cysteine, respectively) is an amino acid that is required for normal functioning of humans. The substance is of low toxicological activity. Therefore, reprotoxic effects are not expected for L-Cystine (and L-Cysteine, respectively) and no test is required for this substance. There is sufficient weight of evidence for the absence of reprotoxic effects. Therefore, in accordance with Annex X 8.9.1 column 2 and because of reasons of animal welfare, a study on carcinogenicity is not deemed necessary.

Additional information

Extensive pathologic calcification was observed in strain A mice 14 and 17 months of age that had been fed a low cystine-low protein diet for 14 and 17 months. The deficient diets exerted an inhibitory effect on the development of the type of nephritis that commonly occurs in strain A mice. Throughout the carious groups there was a correlation between the appearance of nephritis and of amyloidosis.

Justification for selection of carcinogenicity via oral route endpoint:
After an extended literature search one study was found. The study is from 1945 and has to be rated as Klimisch 3 due to the unsuitable test system.As cystine-depletion was examined instead of a cystine overdose, the adverse effects observed in the study don`t need to be considered.