Arginine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No other studies.

Link to relevant study records

Reference

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the extended one-generation reproductive toxicity study does not need to be conducted because there are no results from available repeated dose toxicity studies that indicate adverse effects on reproductive organs or tissues, or reveal other concerns in relation with reproductive toxicity

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
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 very low toxicological activity and subject to homeostasis. Therefore, reprotoxic effects are not expected for L-arginine and no test is required for this substance.
Furthermore, a QSAR for the endpoint reproductive toxicity predicts no toxicity to reproduction.
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 homeostasis.
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.
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.

There is sufficient weight of evidence for the absence of reprotoxic effects. A screening for reproductive toxicity (REACH Annex VIII No. 8.7.1) as well as any study on reproductive toxicity 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..."

Reproductive effects observed:

not specified

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no studies for reproductive toxicity/developmental toxicity of L-arginine accessible to the registrant.

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 homeostasis.

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.

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.

Short description of key information:

It is not expected that L-arginine does affect fertility. No test is required for this substance.

Effects on developmental toxicity

Description of key information

It is not expected that L-arginine does show developmental toxicity / teratogenicity. No test is required for this substance.

Link to relevant study records

Reference

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
L-arginine is an amino acid that is required for normal functioning of humans. The substance is of very low toxicological activity and subject to homeostasis. Therefore, reprotoxic/developmental effects are not expected for L-arginine and no test is required for this substance.
Furthermore, a QSAR for the endpoint reproductive toxicity predicts no toxicity to reproduction.
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 homeostasis. 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..."

Species:

rat

Abnormalities:

not specified

Developmental effects observed:

not specified

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Regarding reproductive toxicity/developmental toxicity no study reports for L-arginine are accessible to the registrant. 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 homeostasis. 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.

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..."

Justification for classification or non-classification

There is no indication that L-arginine causes toxicity to reproduction. Thus, classification as to reproductive toxicity according to EU-GHS is not required.