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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No other studies.
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

Regarding reproductive toxicity/fertility no study reports for L-proline are available to the registrant. A significant amount of L-proline 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-proline from uses which are covered by this registration would only marginally increase the total daily L-proline 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-proline taken up via any use covered by this registration would result in systemic effects. Two repeated dose toxicity studies consistently indicate the very low toxicity of L-proline. 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 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..."


Short description of key information:
Fertility is not expected to be affected by L-proline and no test is required for this substance.

Effects on developmental toxicity

Description of key information
It is expected that L-proline does not show developmental toxicity / teratogenicity.
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-proline are accessible to the registrant.

A significant amount of L-proline 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-proline from uses which are covered by this registration would only marginally increase the total daily L-proline 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-proline taken up via any use covered by this registration would result in systemic effects including effects on unborn life.

This is supported by a Segment II (teratogenicity and embryo toxicity) study in rats which is known to the registrant. As L-proline is used as an excipient for Privigen® the study was conducted to prove the non-hazardous properties of L-proline with regard to developmental toxicity. L-proline doses of 1449 mg/kg/day were administered i.v. during 7 hours/day during Days 6 to 17 of gestation. This dose corresponds to 42 mL L-proline solution/kg bw and represents the maximal daily dose that can be infused in the animals. L-proline showed no indication of maternal or embryo-toxicity.

Although the full study report is not accessible to the registrant the summary (PRODUCT MONOGRAPH Privigen) clearly indicates the absence of adverse effects with regard to developmental toxicity.

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..."

Reference:

PRODUCT MONOGRAPH Privigen® Immune Globulin Intravenous (Human) 10 % Solution for infusion Passive Immunizing Agent

Justification for classification or non-classification

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

Additional information