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Genetic toxicity: in vitro

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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

Referenceopen allclose all

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 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

Constituent 1
Chemical structure
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
Controlsopen allclose all
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
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
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
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).