Atrazine

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:

key study

Study period:

from 01 October 1986 to 13 November 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study design states it complies and it follows OECD guideline 471. Contains sufficient detail to suggest GLP-like characteristics even though no statement of certification is reported (reasonably thorough description of authors, dates, design, results, and interpretation).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

the data have not been statistically analysed

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Literatures ( see Principles of method)

Deviations:

not specified

Principles of method if other than guideline:

1. AMES, B.N., F.D. LEE and W.E. DURSTON (1973), An Improved Bacterial Pest System for the Detection and Classification of Mutagens and Carcinogens. Proc. Natl. Acad. Sci. USA 70, 782786.
2. AMES, B.N., W.E. DURSTON, E. YAMASAKI and F.D. LEE (1973) ,Car cinogens are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection. Proc. Natl. Acad. Sci. USA 70, 22812285.
3. AMES, B.N., J. McCANN, and E: YAMASAKI (1975), Methods for Detecting Carcinogens and Mutagens with the Salmonella/Mammalian Microsome Mutagenicity Test. Mutation Res. 31, 347364.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Atrazine

EC Number:

217-617-8

EC Name:

Atrazine

Cas Number:

1912-24-9

Molecular formula:

C8H14ClN5

IUPAC Name:

6-chloro-N2-ethyl-N4-(propan-2-yl)-1,3,5-triazine-2,4-diamine

Details on test material:

Batch No. lot. 210200
Purity: 98.2%

Method

Target gene:

bacteria

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other: histidine-auxotrophic mutants

Metabolic activation:

with and without

Metabolic activation system:

S9 fraction of liver from rats induced with Aroclor 1254

Test concentrations with justification for top dose:

the test were performed with the following concentrations of the trial substance with and without microsomal activation: 20, 78, 313, 1250 and 5000 µg/0.1 ml.

Vehicle / solvent:

Dimethylsulfoxide (DMSO)

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

DMSO alone has been used as negative controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

for the strain TA 100

Migrated to IUCLID6: 0.125 and 0.25 µg/0.1 ml phosphate buffer

Controls 2

Untreated negative controls:

yes

Remarks:

DMSO alone has been used as negative controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: daunorubicin-HCl, 5 and 10 µg/0.1 ml phosphate buffer

Remarks:

for the strain TA 98

Controls 3

Untreated negative controls:

yes

Remarks:

DMSO alone has been used as negative controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

for the strain 1535

Migrated to IUCLID6: 2.5 and 5 µg/0.1 ml bidistilled water

Controls 4

Untreated negative controls:

yes

Remarks:

DMSO alone has been used as negative controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 9(5)-aminoacridine hydrochloride monohydrate, 50 and 100 µg/0.1 ml DMSO

Remarks:

for strains TA 98, TA 100 and TA 1537

Controls 5

Untreated negative controls:

yes

Remarks:

DMSO alone has been used as negative controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

for the strain TA 1535

Migrated to IUCLID6: 250 µg/0.1 ml bidistilled water

Details on test system and experimental conditions:

In the experiments without and with the addition of microsomal activation mixture three Petri dishes are prepared per strain and per group (i.e. per concentration or per control group).
The plates are incubated for about 48 hours at 37 ± 1.5°C in darkness.

Evaluation criteria:

Assay acceptance criteria:
A test is considered acceptable if the mean colony counts of the control values of all strains are within the acceptable ranges indicated in table 9 and if the results of the positive controls meet the criteria for a positive response.
In either case the final decision has to be based on scientific judgement.

Statistics:

Criteria for a positive response
The test substance is considered to be positive in this test system if one or both of the following conditions are met:
a reproducible doubling of the mean number of revertants per plate above that of the negative control at any concentration level for one or more of the following strains: TA 98, TA 1535 and TA 1537,
a reproducible increase of the mean number of revertants per plate for any concentration above that of the negative control by a factor of l.5 for strain TA 100.
Generally a concentration-related effect should be demonstrable.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In the toxicity tests treatment of the bacteria with the highest concentration (5000 µg/0.l ml) of Atrazine tech. did not lead to a growth-inhibiting effect. This concentration was therefore selected as the highest in the mutagenicity tests.
In the experiments performed without and with microsomal activation, treatment with Atrazine tech. did not lead to an increase in the incidence of histidine-prototrophic mutants in comparison with the negative control.
Owing to a growth-inhibiting effect of the test substance in the experiments without and with microsomal activation, the number of back-mutants was reduced at the highest concentration.

Remarks on result:

other: other: all strains

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative