(+)-L-arginine hydrochloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Read across from L-arginine to L-arginine-HCl is justified for developmental toxicity / teratotengicity. L-arginine-HCl is present as L-arginine under physiological conditions and in human body fluids.

L-arginine did not show effects on the reproductive organs in general repeated dose toxicity studies. Moreover, L-arginine is an amino acid that is required for normal functioning of humans. The substance is of low toxicological activity and subject to homeostasis. Therefore, effects as to developmental toxicity / teratogenicity are not expected for L-arginine and no test is required for this substance.
A significant amount of L-arginine 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-arginine from uses which are covered by this registration would only marginally increase the total daily L-arginine dose 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 homeosasis. Therefore it is highly unlikely that L-arginine taken up via any use covered by this registration would result in systemic effects including effects on unborn life.
Several repeated dose toxicity studies consistently indicate the very low toxicity of L-arginine. Even in very high doses no toxicity is observed and no adverse effects were reported for the reproductive organs.
There is sufficient weight of evidence for the absence of developmental toxicity / teratogenicity. Any study on developmental toxicity / teratogenicity as REACH Annex IX no. 8.7 are not to be conducted in accordance with REACH Annex XI no. 1.2. and for reasons of animal welfare: "Where sufficient weight of evidence for the presence or absence of a particular dangerous property is available, further testing on vertebrate animals for this property shall be omitted..."

Materials and methods

Test animals

Species:

rat

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified