Registration Dossier

Administrative data

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:
other:
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

Read across from L-arginine to L-arginine-HCl is justified for toxicity to reproduction, too. L-arginine-HCl is present as L-arginine under physiological conditions and in human body fluids.

There are no studies for reproductive toxicity/developmental toxicity of L-arginine (and of L-arginine-HCl) 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 or L-arginine-HCl 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 or L-arginine-HCl taken up via any use covered by this registration would result in systemic effects including effects on unborn life.

Short description of key information:

Read across from L-arginine to L-arginine-HCl is performed. L-arginine-HCl is present as L-arginine under physiological conditions and in human body fluids.

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

Effects on developmental toxicity

Description of key information

Read across from L-arginine to L-arginine-HCl is performed. L-arginine-HCl is present as L-arginine under physiological conditions and in human body fluids.

It is not expected that L-arginine and from this L-arginine-HCl 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:
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

Read across from L-arginine to L-arginine-HCl is justified for developmental toxicity / teratogenicity, too. L-arginine-HCl is present as L-arginine under physiological conditions and in human body fluids.

 

Regarding reproductive toxicity/developmental toxicity no study reports for L-arginine (and of L-arginine-HCl) 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 or L-arginine-HCl from uses which are covered by this registration would only marginally increase the total daily L-arginine dose (taken up as L-arginine or L-arginine-HCl) 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 or L-arginine-HCl 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-HCl causes toxicity to reproduction. Thus, classification as to reproductive toxicity according to EU-GHS is not required.