Dexpanthenol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1998-07-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

July 21, 1997

Deviations:

yes

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

December 1992

Deviations:

yes

Principles of method if other than guideline:

Deviation:
The stability of the test substance in the vehicle water has not been determined analytically.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Panthenol , DL-form

EC Number:

240-540-6

EC Name:

Panthenol , DL-form

Cas Number:

16485-10-2

Molecular formula:

C9H19NO4

IUPAC Name:

2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutanamide

Constituent 2

Reference substance name:

DL-Panthenol

IUPAC Name:

DL-Panthenol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Method

Target gene:

his operon

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S-9

Test concentrations with justification for top dose:

20, 100, 500, 2500, 5000 µg/plate (SPT and PIT)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Due to the good solubility of the test substance in water, water was selected as the vehicle.

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro-o-phenylendiamine, 9-aminoacridine, 4-nitroquinoline-N-oxide

Remarks:

positive control substance depending on tester strain and activation conditions

Details on test system and experimental conditions:

METHOD OF APPLICATION: (plate incorporation)
DURATION
- Exposure duration: 48 - 72 h, 37°C, in the dark
NUMBER OF REPLICATIONS: 3 plates per dose or per control
DETERMINATION OF CYTOTOXICITY
- Method: decrease in the number of revertants, clearing or diminution of the background lawn (= reduced his- or trp+ background growth), reduction in the titer

METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min., 37°C
- Exposure duration: 48 - 72 h, 37°C, in the dark
NUMBER OF REPLICATIONS: 3 plates per dose or per control
DETERMINATION OF CYTOTOXICITY
- Method: decrease in the number of revertants, clearing or diminution of the background lawn (= reduced his- or trp+ background growth), reduction in the titer

Evaluation criteria:

Acceptance criteria
Generally, the experiment is to be considered valid if the following criteria are met:
The number of revertant colonies in the negative controls was within the normal range of the historical control data for each tester strain.
The sterility controls revealed no indication of bacterial contamination.
The positive control articles both with and without S-9 mix induced a significant increase in the number of revertant colonies within the range of the historical control data.
The titer of viable bacteria was >10E9/ml.

Evaluation criteria
The test chemical is considered positive in this assay if the following criteria are met:
A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one tester strain either without S-9 mix or after adding a metabolizing system.
A test substance is generally considered nonmutagenic in this test if:
The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments carried out independently of each other.

Statistics:

no data

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

No increase in the number of revertants was observed with any tester strain at any concentration in the absence and presence of metabolic activation. No bacteriotoxicity was observed. The test substance was completely soluble in the vehicle; no precipitation was noted.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

According to the results of the present study, DL-Panthenol was considered to be not mutagenic.

Executive summary:

A read across approach was performed on data available for a substance with similar physical-chemical properties. The substance D,L-Panthenol was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay.

Standard plate test (SPT) and Preincubation Test (PIT) both with and without metabolic activation with liver homogenate of Aroclor 1254 -pretreated male Sprague-Dawley rats were applied. Two independent experiments were carried out:

1st Experiment

Strains: TA 1535, TA 100, TA 1537, TA 98, E. coli WP2 uvrA

Doses: 0; 20; 100; 500; 2500 and 5000 µg/plate

Vehicle: Water

Type of test: Standard plate test with and without S-9 mix

Number of plates: 3 test plates per dose or per control

2nd Experiment

Strains: TA 1535, TA 100, TA 1537, TA 98, E. coli WP2 uvrA

Doses: 0; 20; 100; 500; 2500 and 5000 µg/plate

Vehicle: Water

Type of test: Preincubation test with and without S-9 mix

Number of plates: 3 test plates per dose or per control

Negative controls treated with the vehicle (water) and positive controls treated with 2-aminoanthracene, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro-o-phenylendiamine, 9-aminoacridine, or 4-nitroquinoline-N-oxide were included in each replicate.

D,L-Panthenol was not mutagenic in the bacterial reverse mutation test using bacteria.