Phosphatidylcholines, soya, hydrogenated

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The genotoxicity of hydrogenated soya phosphatidylcholine was investigated in the Salmonella typhimurium (Ames test) and Escherichia coli Reverse mutation Assay. The study was conducted according to the OECD Guidelines 471/472 and following GLP.

Hydrogenated soya phosphatidylcholine caused no mutagenic effects at concentrations ranging from 8-5000 µg/plate

Data on mammalian cells are not available for Phosphatidylcholines, soya, hydrogenated. A weight of evidence approach with data on non-hydrogenated lecithins, which are very similar in structure and similar behaviour can be considered.

Based on the studies described in the assessment on similar lecithins, there are no indications of genotoxic activity in any of the tested lecithins. For further details, please refer to the weight of evidence assessment attached in the specific endpoint.

Based in the above it is concluded that the compound phosphatidylcholines, soya, hydrogenated is not genotoxic.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995.07.28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Batch no. 42000100
white crystalline powder
expiry date 7/1996

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

10-10.000 µg/plate. No bacteriotoxic effects were observed however precipitation in the range from 1000-10.000 µg/plate therefore the following concentrations were applied:
8, 40, 200, 1000 and 5000 µg/plate

Vehicle / solvent:

ethanol

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

N-ethyl-N-nitro-N-nitrosoguanidine

other: 4-nitro-1,2-phenylene diamine and 2-aminoanthracene

Details on test system and experimental conditions:

The positive controls (without the S 9 mix):
sodium azide (10µg/plate used for TA 1535 and TA 100) ,
9-aminoacridine hydrochloride (50µg/plate used for TA 1537)
4-nitro-1,2 phenylene diamine (10µg/plate used for TA 1537 and TA 98)
and N-ethyl N-nitro nitrosguanidin (5 µg/plate used for E. coli WP2 uvrA and pKM101)

The positive control 2-aminoantracene (3 and 40 µg/plate) was used for positive control for tests with S9 metabolic activation
Negative control: Solvent without test article

Evaluation criteria:

Criteria for acceptance of assay:
- The negative controls had to be within the expected range as defined by published data (Maron and Ames 1983)
- The positive controls had to show sufficient effects as defined by the laboratory's experience
- The titer determination had to reveal a sufficient bacterial density in the suspension

Assessment of mutagenicity and baceriotoxicity:
A reproducible and dose-related increase of mutants counts for at least one strain is considered positive
For TA 98, TA 1535, WP2 uvrA and WP2 CM a twofold increase of revernants compared to the negative controls should be reached, whereas for TA 1537 a threefold increase should be attained. For TA 100 a 1.5-fold increase is regarded as an indication of potential mutagenicity. Otherwise the results are considered to be negative.

The criterion for a biologically significant bacteriotoxic effect is a reduction in the number of colonies/plate or revernants/plate or in background growth by more than 50% relative to the respective negative control.

Statistics:

NA

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Positive controls validity:

valid

Additional information on results:

Hydrogenated soya phosphatidylcholine caused no mutagenic effects at concentrations ranging from 8-5000 µg/plate

Remarks on result:

other: No mutagenic nor bacteriotoxic effects at concentrations ranging from 8-5000 µg/plate

Conclusions:

Hydrogenated soya phosphatidylcholine caused no mutagenic effects at concentrations ranging from 8-5000 µg/plate.

Executive summary:

Hydrogenated soya phosphatidylcholine was investigated in the Salmonella typhimurium (Ames test) and Escherichia coli Reverse mutation Assay for point mutations using Salmonella Typhimurium LT2 mutants and two E.coli WP2 mutants. These two tester strains were the histidine auxotrophic Salmonella strains TA1535, TA 1537, TA 98, Ta 100 and the trypto auxotrophic E. coli strains WP2 uvrA and WP2 uvr (pkM101). The study was conducted according to the OECD Guidelines 471/472 and following GLP.

Hydrogenated soya phosphatidylcholine caused no mutagenic effects at concentrations ranging from 8-5000 µg/plate.

In the positive control the mutant counts increased to more than twice the value of the negative controls, demonstrating that the system was highly sensitive.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

other: Weight of evidence analysis based on expert evaluated data on the group of lecithins

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews and published data

Justification for type of information:

Data on this endpoint are not available for Phosphatidylcholines, soya, hydrogenated.
As the substance belongs to the group of lecithins that are commonly used in cosmetics and used as food ingredient, reviews and expert group assessments of the substances are considered the most valid data available. In order to combine data on several similar substances an overall weight of evidence approach is used for the assessment. In order to assess the in vitro gene mutation study in mammalian cells of hydrogenated phosphatidylcholines, gene mutation studies in mammalian cells with non-hydrogenated lecithins, which are very similar in structure and similar behaviour can be considered. In the present analysis, data on phosphatidylcholines and phospatidylserines are used.
The group of lecithins has been evaluated by the expert groups EFSA and CIR, where this approach was also used. The reports are attached below.

Principles of method if other than guideline:

The conclusion is based on a collection of data performed equivalent or similar to relevant guidelines. However, details on methods may vary. Please refer to attached weight of evidence document.

Type of assay:

other: Several assays was applied. Please see attached weight of evidence document for further details

Specific details on test material used for the study:

For more details, please see attached weight of evidence document.

Key result

Species / strain:

other: Human embryonic epithelium (EUE) cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

other: Cultured human epithelioid cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Conclusions:

Based on the studies available in the present analysis it is concluded that the compound phosphatidylcholines, soya, hydrogenated is not genotoxic.

Executive summary:

Several studies on genetic toxicity are described with different versions of lecithin. All studies of reverse mutation assays with bacteria using lecithins are negative, including one study with hydrogenated lecithin.

Unscheduled DNA synthesis was investigated in human embryonic epithelium (EUE) cells exposed to a multivitamin preparation containing lecithin (50 mg/ml). No indication of inductionofunscheduled DNA synthesis was found.

Two studies were performed on the genotoxic potential of phosphatidylserine from bovine brain tissue (BC-PS). No genotoxicity was found in either mouse lymphoma L5178Y cells or cultured human epithelioid cells (HELA S3). All tests were carried out with and without metabolic activation. Further, an in vivo micronucleus test in mice was performed. No cytogenetic damage was detected.

Based on the studies described above on similar lecithins, there are no indications of mutagenic activity in any of the tested lecithins. Based on an overall weight of evidence approach, it is therefore concluded that the compound phosphatidylcholines, soya, hydrogenated is not mutagenic.

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

other: Weight of evidence analysis based on expert evaluated data on the group of lecithins

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews and published data

Justification for type of information:

Data on this endpoint are not available for Phosphatidylcholines, soya, hydrogenated.
As the substance belongs to the group of lecithins that are commonly used in cosmetics and used as food ingredient, reviews and expert group assessments of the substances are considered the most valid data available. In order to combine data on several similar substances an overall weight of evidence approach is used for the assessment.
In order to assess the cytogenicity in mammalian cells of hydrogenated phosphatidylcholines, studies in mammalian cells with non-hydrogenated lecithins, which are very similar in structure and similar behaviour can be considered. In the present analysis, data on phosphatidylcholines and phospatidylserines are used.
The group of lecithins has been evaluated by the expert groups EFSA and CIR, where this approach was also used. The reports are attached below.

Principles of method if other than guideline:

The conclusion is based on a collection of data performed equivalent or similar to relevant guidelines. However, details on methods may vary. Please refer to attached weight of evidence document.

Type of assay:

other: Several assays was applied. Please see attached weight of evidence document for further details

Specific details on test material used for the study:

For more details, please see attached weight of evidence document.

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

lymphocytes: human

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Untreated negative controls validity:

valid

Conclusions:

Based on the studies available in the present analysis it is concluded that the compound phosphatidylcholines, soya, hydrogenated is not genotoxic.

Executive summary:

Several studies on genetic toxicity are described with different versions of lecithin. All studies of reverse mutation assays with bacteria using lecithins are negative, including one study with hydrogenated lecithin.

Regarding cytogenicity, chromosomal aberration (OECD 473) was investigated in Chinese hamster lung fibroblast cells

exposed to purified phosphatidylinositol from soya. No chromosomal aberrations were detected.

One study was performed on the genotoxic potential of phosphatidylserine from bovine brain tissue (BC-PS). No chromosomal damage was found in human cultured lymphocytes. All tests were carried out with and without metabolic activation. Further, an in vivo micronucleus test in mice was performed. No cytogenetic damage was detected.

Based on the studies described above on similar lecithins, there are no indications of genotoxic activity in any of the tested lecithins. Based on an overall weight of evidence approach, it is therefore concluded that the compound phosphatidylcholines, soya, hydrogenated does no induce cytogenetic damage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

The genotoxicity of hydrogenated soya phosphatidylcholine was investigated in the Salmonella typhimurium (Ames test) and Escherichia coli Reverse mutation Assay. The study was conducted according to the OECD Guidelines 471/472 and following GLP.

Hydrogenated soya phosphatidylcholine caused no mutagenic effects at concentrations ranging from 8-5000 µg/plate

Data on mammalian cells are not available for Phosphatidylcholines, soya, hydrogenated. A weight of evidence approach with data on non-hydrogenated lecithins, which are very similar in structure and similar behaviour can be considered.

Based on the studies described in the assessment on similar lecithins, there are no indications of genotoxic activity in any of the tested lecithins.For further details, please refer to the weight of evidence assessment attached in the specific endpoint.

Based in the above it is concluded that the compound phosphatidylcholines, soya, hydrogenated is not genotoxic.