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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:
year completed 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD guideline with GLP, acceptable with restrictions (only 4 strains were used)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: NTP standard protocol according to Zeiger et al 1992
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not applicable
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): p,p'-Dichlorodiphenyl Sulfone
- Physical state: white powder
- Analytical purity: > 99%
- Lot/batch No.: AX01 (TCI America, Portland), P02300 (Lancaster Synthesis Inc., Windham) aliquot delivered via Radian Corporation (Austin, TX)

Method

Target gene:
Salmonella typhimurium: histidine operon
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 100
Species / strain / cell type:
S. typhimurium TA 1535
Species / strain / cell type:
S. typhimurium TA 97
Species / strain / cell type:
S. typhimurium TA 98
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced male Sprague-Dawley rat and Syrian hamster liver
Test concentrations with justification for top dose:
0, 10, 33, 100, 333, and 1000 µg/plate
Vehicle / solvent:
- Vehicle/solvent used: no data
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine
Remarks:
strain TA98 in the absence of metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
strains TA100 and TA1535 in the absence of metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
strain TA97 in the absence of metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
with all strains with metabolic activation
Details on test system and experimental conditions:
Testing was performed as reported by Zeiger et al. (1992). DCDPS was incubated with the Salmonella typhimurium tester strains TA97, TA98, TA100, and TA1535 either in buffer or S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver) for 20 minutes at 37° C.
Top agar supplemented with L-histidine and d-biotin was added, and the contents of the tubes were mixed and poured onto the surfaces of minimal glucose agar plates. Histidine-independent mutant colonies arising on these plates were counted following incubation for 2 days at 37° C.
Each trial consisted of triplicate plates of concurrent positive and negative controls and five doses of DCDPS. The high dose was limited by solubility. All trials without S9 were repeated. Trials initially performed with 10% S9 were repeated with 30% S9.

Zeiger et al (1992). Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. PMID: 1541260, Environ Mol Mutagen 19(Suppl 21):2-141
Evaluation criteria:
A positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity.
A negative response is obtained when no increase in revertant colonies is observed following chemical treatment.

Results and discussion

Test results
Species / strain:
other: TA100, TA 535, TA97, TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: the test substance precipitated at 100 µg/plate and above
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table from NIH (2001, NTP TR 501, p. 197)

Mutagenicity of DCDPS in Salmonella typhimuriuma

Strain                  Dose

[µg/plate]

 

 

 

Revertants/Plateb

 

 

-S9

 

+hamster S9

+rat S9

Trial 1

Trial 2

10%

30%

10%

30%

TA100                               0

127 ± 15.1

110 ± 7.1

123 ± 8.0

161 ± 11.9

135 ± 7.2

159 ± 2.3

10

121 ± 2.1

116 ± 8.2

134 ± 8.8

156 ± 9.4

118 ± 11.9

152 ± 2.1

33

130 ± 3.8

90 ± 5.3

130 ± 8.3

143 ± 1.5

128 ± 10.2

171 ± 4.4

100c

104 ± 8.3

124 ± 0.6

155 ± 2.8

148 ± 7.4

121 ± 10.2

139 ± 4.1

333c

131 ± 0.9

105 ± 5.5

131 ± 7.3

158 ± 9.3

109 ± 7.2

164 ± 7.3

1,000c

137 ± 3.0

128 ± 14.4

131 ± 4.7

149 ± 5.4

119 ± 5.9

165 ± 9.5

Trial summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive controld

561 ± 9.5

573 ± 13.5

479 ± 10.0

471 ± 15.7

1,525 ± 64.2

491 ± 20.5

TA1535                            0

8 ± 1.7

10 ± 0.6

11 ± 2.4

10 ± 1.5

8e

12 ± 1.7

10

8 ± 0.9

9 ± 1.2

12 ± 2.3

13 ± 0.9

9 ± 1.2

12 ± 1.7

33

9 ± 0.7

9 ± 0.9

9 ± 0.6

11 ± 0.3

8 ± 1.2

12 ± 1.2

100c

7 ± 0.7

12 ± 2.4

10 ± 1.8

11 ± 2.6

7 ± 1.5

13 ± 2.0

333c

9 ± 1.0

9 ± 1.2

7 ± 0.9

9 ± 2.2

9 ± 1.5

12 ± 1.3

1,000c

11 ± 0.7

9 ± 1.7

7 ± 1.0

13 ± 2.3

6 ± 2.0

11 ± 2.4

Trial summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

159 ± 15.4

371 ± 22.0

50 ± 8.6

66 ± 4.9

158 ± 6.2

140 ± 9.1

TA97                                 0

134 ± 5.3

151 ± 4.2

164 ± 5.8

138 ± 4.3

159 ± 4.7

188 ± 3.2

10

127 ± 0.9

161 ± 8.0

157 ± 3.8

145 ± 6.4

133 ± 4.0

187 ± 5.5

33

140 ± 5.2

158 ± 7.5

128 ± 5.9

149 ± 5.1

160 ± 5.4

193 ± 12.9

100c

125 ± 7.5

142 ± 7.3

161 ± 3.2

160 ± 8.1

166 ± 9.5

189 ± 5.6

333c

139 ± 16.8

141 ± 9.2

154 ± 6.9

158 ± 7.4

149 ± 19.0

180 ± 3.1

1,000c

127 ± 8.1

125 ± 2.9

151 ± 8.4

171 ± 2.4

108 ± 5.9

185 ± 4.9

Trial summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

353 ± 9.8

347 ± 9.6

992 ± 8.1

661 ± 5.2

1,719 ± 31.5

561 ± 39.8

TA98                                 0

16 ± 1.5

15 ± 2.6

15 ± 1.3

25 ± 5.2

19 ± 0.9

24 ± 1.2

10

10 ± 0.9

15 ± 2.7

20 ± 0.9

27 ± 3.9

18 ± 1.5

24 ± 2.7

33

13 ± 2.0

11 ± 3.1

20 ± 2.2

31 ± 1.0

21 ± 2.0

27 ± 0.9

100c

13 ± 3.7

15 ± 1.9

18 ± 0.7

22 ± 4.4

18 ± 1.2

25 ± 1.2

333c

11 ± 1.5

16 ± 1.9

21 ± 2.8

18 ± 1.9

19 ± 0.3

26 ± 1.9

1,000c

17 ± 1.8

11 ± 0.6

17 ± 2.6

31 ± 5.4

23± 1.7

33 ± 2.3

Trial summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

286 ± 17.5

278 ± 3.8

419 ± 33.2

465 ± 20.7

458 ± 23.7

239 ± 8.1

 a Study was performed at Microbiological Associates. The detailed protocol is presented by Zeiger et al. (1992). 0 µg/plate was the solvent control.

b Revertants are presented as mean ± standard error from three plates.

c Precipitate on all plates

d The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), and 4-nitro-o-phenylenediamine (TA98). The positive control for metabolic activation with all strains was 2-aminoanthracene.

e Results available from a single plate only

No significant dose related increase in the number of revertants were observed in all 4 strains. Under the condition of this assay, the compound was concluded to be not mutagenic with and without metabolic activation system.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Under the all test conditions DCDPS gave an unequivocal negative response. DCDPS (10 to 1,000 µg/plate) was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without induced rat or hamster liver S9 metabolic activation enzymes.
Executive summary:

DCDPS was tested for mutagenicity in Salmonella typhimurium strains TA97, TA98. TA100, and TA1535 according to the method published by Zeiger et al 1992 (NIH 2001). The protocol is comparable to the OECD TGD 471 standards.

The applied doses were 0, 10, 33, 100, 333, and 1000 µg/plate. Each concentration was tested in triplicates. Concurrent vehicle and positive controls were included.

The tests were conducted using a preincubation protocol in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. DCDPS was not cytotoxic. It precipitated at concentrations of 100 µg/plate and higher. DCDPS gave an non-mutagenic response under all conditions.