1-chloro-4-nitrobenzene

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:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Salmonella mutagenicity test results for 250 chemicals.

Author:

Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E (1983)

Year:

1983

Bibliographic source:

Environm Mutagen 5[Suppl.1]: 3-142

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

: only four strains used

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-4-nitrobenzene

EC Number:

202-809-6

EC Name:

1-chloro-4-nitrobenzene

Cas Number:

100-00-5

Molecular formula:

C6H4ClNO2

IUPAC Name:

1-chloro-4-nitrobenzene

Details on test material:

- Name of test material (as cited in study report): 1-chlor-4-nitrobenzene
- Analytical purity: > 99 %

Method

Target gene:

his-operon

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9-Mix

Test concentrations with justification for top dose:

all strains, +/-S9, PM: 0.0, 30, 100, 300, 1000, 3000 µg/plate; add. only TA100,+/-S9, PM: 0.0, 62.5, 250, 500, 1500, 2000 µg/plate

Vehicle / solvent:

DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene only with S9-mix tested: in TA 98, TA 100, TA 1535, TA 1537: with RLI: 1.5 µg/plate and HLI: 0.75 µg/plate

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine in TA 98, without S9: 12.0 µg/plate

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

Migrated to IUCLID6: in TA 100 and TA 1535 with S9-mix: 2.5 µg/plate

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Migrated to IUCLID6: only in TA 1537 without S9-mix: 80.0 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation methodology (PM), add. TA100: standard plate methodology (SPM)



NUMBER OF REPLICATIONS: performed in triplicate and repeated twice


DETERMINATION OF CYTOTOXICITY
- Method: other: viability on complete medium



OTHER: study performed with rat liver S9-mix and hamster liver S9-mix

Evaluation criteria:

A positive response was indicated by a reproducible, dose-related, increase, whether it be twofold over background or not.

Statistics:

according to Margolin et al. 1981

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 1500 mg/plate (TA100); at 3000 mg/plate (TA98, TA1535 and TA1537)

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: S. typhimurium TA 98, TA 100, TA 1535, TA 1537

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 55.1a

4 -Chloronitrobenzene       [DMSO]

TA100

TA1535

TA1537

TA98

Dose

NA

RLI

HLI

NA

RLI

HLI

NA

RLI

HLI

NA

RLI

HLI

0.0 30.0 100.0 300.0 1000.0 3000.0

98±3.3 93±3.8 93±4.8 82±5.5 81±4.1 28±9.0

98±9.2 94±2.6 108±3.5 129±6.7 192±3.3 57±17.8

117±7.2 137±12.3 152±7.8 152±17.6 255±28.0 25±17.4

12±2.1 11±2.3 9±1.2 13±0.6 13±1.5 8±1.5

9±1.2 11±0.3 8±1.2 6±0.7 15±1.8 10±1.9

9±2.3 8±1.2 12±0.6 15±1.8 14±1.5 3±2.0

6±1.5 8±0.9 6±1.5 5±1.2 5±0.9 2±1.2

9±1.2 10±1.5 5±1.5 7±0.3 7±1.8 3±2.2

6±0.3 10±0.6 8±2.3 8±1.7 7±1.0 5±1.8

17±1.8 17±2.0 22±4.3 21±1.5 18±2.0 10±0.3

26±1.5 17±2.8 22±5.3 25±0.7 15±2.7 9±2.0

29±3.3 25±3.2 25±3.2 25±3.2 45±6.1 24±4.9

POS

1270±4.5

2356±38.1

3212±76.1

929±43.8

87±19.2

189±31.8

320±29.3

158±6.1

298±11.7

1444±58.4

2270±61.5

2739±69.7

Table 55.1b                                          

4 -Chloronitrobenzene       [DMSO] (only TA100 tested)

TA100

TA1535

TA1537

TA98

Dose

NA

RLI

HLI

NA

RLI

HLI

NA

RLI

HLI

NA

RLI

HLI

0.0 30.0 100.0 300.0 1000.0 3000.0

128±3.3 150±5.0 136±5.8 116±4.4 114±4.7 25±13.9

113±10.2 138±0.3 143±5.4 172±12.6 201±21.1 37±22.9

105±6.7 131±5.8 136±4.4 147±6.5 178±4.5 98±14.2

POS

1987±29.7

1264±52.9

2032±30.8

Table 55.1c

4 -Chloronitrobenzene       [DMSO] (only TA100 tested)

TA100

TA1535

TA1537

TA98

Dose

NA

RLI

HLI

NA

RLI

HLI

NA

RLI

HLI

NA

RLI

HLI

0.0 62.5 250.0 500.0 1000.0 1500.0 2000.0

117±13.5 99±3.5 99±2.6 81±6.0 94±4.3 69±4.4 61±4.4

118±10.3 137±6.6 155±6.1 176±5.9 183±6.1 168±6.3 174±0.9

112±3.7 132±7.1 158±13.7 200±11.0 235±20.3 189±11.6 148±15.2

POS

2321±123.2

2232±45.4

3005±74.6

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive with metabolic activation only in TA 100

Executive summary:

Harworth et al., 1983

The mutagenic activity of 1 -chloro-4-nitrobenzene was investigated in a bacterial gene mutation assay conducted similar to OECD-guideline 471. The preincubation assay was performed with Salmonella typhimurium TA98, TA 100, TA1535 and TA1537 both in presence and absence of a metabolic activator (induced rat and hamster liver S9 -mix) at 0.0, 30, 100, 300, 1000, 3000 µg and additionally in TA100 with and without S9 -mix at 0.0, 62.5, 250, 500, 1500, 2000 µg 1 -chloro-4 -nitrobenzene per plate.

The test compound induced mutations in presence of an metabolic activator (hamster liver S9 -mix stronger than with rat liver S9 -mix) in the strain TA100 (up to 2.2 times higher than control).