Erythromycin

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

July 12-29, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with GLP. Study material is well characterized. Protocol was si milar to OECD method of its time. Antibiotic toxicity observed at low concentrations- supporting study only.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Principles of method if other than guideline:

This study was conducted in accordance with Department 468 Standard Operating Procedure No.
0468-12-408.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Erythromycin

EC Number:

204-040-1

EC Name:

Erythromycin

Cas Number:

114-07-8

Molecular formula:

C37H67NO13

IUPAC Name:

6-{[4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-[(5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy]-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione (non-preferred name)

Method

Target gene:

Salmonella typhimurium histidine auxotroph bacteria of the following strains were used for the nonac tivated and rat-liver-microsome-activated tests:TA-1535, TA-1537, TA-1538, TA-98 and TA-100

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium: TA1535, TA1537, TA98, TA100, TA1538

Details on mammalian cell type (if applicable):

The strains were received from Dr. Bruce Ames' laboratory, University of California, Berkeley, CA. Frozen cultures were prepared and stored at approximately -62°C. Flasks of nutrient broth were ino culated from the frozen cultures and grown overnight (approximately 18-20 hours) in a 37°C shaking water bath .

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix(2.5%) from Aclor 1254-induced rat liver

Test concentrations with justification for top dose:

The study was conducted at concentrations of 0, 0.4, 0.8, 1.6, 3.1, 6.3, 12.5, 25, 50 and 100 mcg per petri plate.

Vehicle / solvent:

solvent- Dimethyl sulfoxide

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

vehicle controls used in parallel with the test material

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: Quinacrine Mustard (QM) and 2-aminoanthracene

Details on test system and experimental conditions:

Petri plates of Vogel Bonner Medium E agar were prepared at least 24 hours in advance of their use in accordance with Department 468 Standard Operating Procedure No. 0468-11-403.Top agar was prepared according to Department 468 Standard Operating Procedure No .0468-11-404. Each 100 ml of top agar was supplemented with 10 ml of 0.5 mM L-histidine HCl and 0.5 mM biotin

For each petri plate, 0.1 ml of Salmonella broth culture, 0.05 ml of test compound solution and 0.5 ml of S-9 mix (activated tests only) were added to 2.0 ml of molten (approximately 45°C) top agar. The top agar mixture was poured over a hardened Vogel-Bonner medium E agar petri plate and a llowed to harden. Triplicate petri plates were prepared for all test combinations. The petri plates were incubated at approximately 37°C for approximately 48 hours

Statistics:

Mean and standard deviation of the plate counts for each treatment were determined

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Toxicity was seen at 25 mcg and higher in all strains except TA-98 and at 50 mcg and higher in TA-98

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

ABBOTT-56268 showed no mutagenic effect on Salmonella as no increases in the number of colo nies on petri plates treated with test material was seen when compared to the number of colonies on vehicle control petri plates.Toxicity, as evidenced by a reduction in the number of bacterial colonies was seen at 100 and 50 mcg for all strains, at 25 mcg for all strains except TA-98 and at 12.5 mcg for TA-1535, TA-1538 and TA-100

Remarks on result:

other: all strains/cell types tested Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative
No dose-related and reproducible increases in revertant colony frequency were observed in any tester strains at any concentration, both with and without S9. The test substance was not genotoxic in the Ames test