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Toxicological information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Lacks compliance with contemporary guidelines. However this study is considered to provide adequate data for assessment.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977
Reference Type:
secondary source
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Principles of method if other than guideline:
Ames et al ., Mut . Res ., 31, 347-364, (1975)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
MDA, no further data

Method

Species / strain
Species / strain / cell type:
other: TA98, TA100, TA 1537, TA 1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced liver S9 from male sprague dawley rats
Test concentrations with justification for top dose:
3.5-3000 µg/plate
Vehicle / solvent:
- Vehicle/solvent used: DMSO
Controls
Untreated negative controls:
yes
Remarks:
(sterility control)
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: - S9: N-methyl-N'-nitro-N-nitrosoguanidine and Benzo(a)pyrene 4,5-oxide; +S9: 3-methylcholanthrene, benzo(a)pyrene, 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation);
DURATION
- Exposure duration: 2-3 days

Results and discussion

Test resultsopen allclose all
Species / strain:
other: TA 98, TA 100, TA 1537, TA 1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
other: TA 100, TA 98, TA 1538
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
Negative in absence of S-9
Positive in presence of S-9 with TA 100, weakly positive with TA 98 and TA 1538 (dose dependent).
Negative inpresence of S-9 with TA 1537.
Positive with doses of 30 µg/plate, in a dose dependent manner.
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: his+ revertants in presence of S-9 mix

Dose [µg/plate]

TA100

Exp.1

TA100

Exp.1

TA100

Exp.2

TA100

Exp.2

TA1537

TA1537

TA98

TA98

TA1538

TA1538

0

182

202

139

151

12

17

35

47

32

32

0

190

174

143

134

12

11

48

36

32

34

3.15

180

281

-

-

13

13

-

-

-

-

10

270

760

276

326

13

12

69

115

28

-

31.5

840

1060

530

674

13

12

112

105

33

35

100

1260

850

1130

1070

15

14

167

140

52

45

315

1170

1020

1240

1560

10

10

225

217

52

42

1000

2050

2410

-

-

16

17

-

-

-

-

3000

1260

1730

-

-

11

14

-

-

-

-

P1

1300

1390

1390

1280

210

184

800

850

242

280

P2

5800

5300

5600

5800

355

490

5700

4900

1960

2110

P3

5600

4600

2950

2820

118

108

1470

1510

87

64

P1 = 10 µg/plate Benzo(a)pyrene

P2 = 10 µg/plate 2-Aminoanthracene

P3 = 90 µg/plate3-Methylcholanthrene

 

- the mutagenic potential was relatively strong with TA 100. The mutagenicity (expressed as mutations per µg of test compound under optimal conditions) of phenylbase, an aromatic amine, was about 25 times weaker with TA 100 than that of the positive control 2-aminoanthracen. In TA 98 and TA 1538 the mutagenic potential was less pronounced than in TA 100.

Similar results from 3 to 333 µg/plate reported by Zieger et al 1988, using rat and hamster liver S-9.

Applicant's summary and conclusion

Conclusions:
Positive in the presence of a metabolic activation system.

NOTE FOR III: This is reported in the EU Risk assessment – original report not in Scientific Office. The SO has a translated document hand marked 77/207, which may be an unofficial translation of the report – this is not marked as to any ownership or test lab, but is signed and dated: Prof F Oesch, Mainz, 13 December 1977