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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable publication (a total of 43 substances were evaluated)

Data source

Reference
Reference Type:
publication
Title:
The results of microbial mutation test for forty-three industrial chemicals
Author:
Shimizu H, Suzuki Y, Takemura N, Goto S and Matsushita H
Year:
1985
Bibliographic source:
Jpn J Ind Health 27: 400-420

Materials and methods

Principles of method if other than guideline:
Ames test
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
3-hydroxy-2-naphthoic acid
EC Number:
202-180-8
EC Name:
3-hydroxy-2-naphthoic acid
Cas Number:
92-70-6
IUPAC Name:
3-hydroxy-2-naphthoic acid

Method

Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100 and E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
prepared from the liver of male SD rats (7 weeks, 220 g) pretreated with polychlorinated biphenyl at dose of 500 mg/kg bw 5 days before sacrifice (the S9-mix contained 0.1 ml of S9/ml)
Test concentrations with justification for top dose:
0, 1, 5, 10, 50, 100, 500, 1000 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility
Controls
Untreated negative controls:
yes
Remarks:
H2O
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
other: a total of 43 substances were tested, 41 of which were negative mutagens
Positive controls:
yes
Remarks:
of the 43 substances tested, 2 were also negative mutagens
Positive control substance:
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), 9-aminoacridine (9AC), 4-nitroquinoline-l-oxide (4NQO), benzo(a)pyrene (B(a)P), 2-aminoanthacene (2AA) and 2-nitrofluorene (12NF)
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation (in duplicates)

DURATION
- Preincubation period: 20 min at 37°C
- Exposure duration: 20 min at 37°C

SELECTION AGENT (mutation assays): histidine or tryptophan deprivation

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
Evaluation criteria:
Not specified, but standard Ames test criteria were followed
Statistics:
None necessary

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100 and E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
no increased of revertant colonies/plate was observed (see Table 1)
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
growth inhibition was observed at the high dose level (5000 µg/plate; see Table 1)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: none observed

COMPARISON WITH HISTORICAL CONTROL DATA:
The test substance was evaluated together with 42 additional compounds, two of which shown mutagenic potency
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Mutagenic activity of the test substance

Test compound

Dose (µg/plate)

Revertant colonies/plate (mean ± standard deviation where indicated)

TA100

TA1535

WP2 uvrA

TA98

TA1537

TA1538

-S9-mix

+S9-mix

-S9-mix

+S9-mix

-S9-mix

+S9-mix

-S9-mix

+S9-mix

-S9-mix

+S9-mix

-S9-mix

+S9-mix

H2O (neg. control)

 

149±17.1

161±16.2

28±6.2

15±3.6

32±7.3

33±10.3

29±6.2

39±8.6

16±6.4

21±8.1

21±5.5

28±7.0

DMSO (neg. control)

 

150±16.8

154±17.5

30±5.6

15±7.1

30±9.7

34±10.9

32±7.7

42±10.1

18±8.6

22±6.3

22±7.3

28±5.7

Acetone (neg. control)

 

179±15.0

136±7.0

23±1.5

8±1.5

30±7.5

26±4.0

24±3.0

32±1.0

10±3.0

18±2.5

21±0.5

26±1.5

AF-2 (pos. control)

0.01

501±84.7

-

-

-

-

-

-

-

-

-

-

-

0.05

-

-

-

-

1082±293.7

-

278±64.8

-

-

-

-

-

ENNG (pos. control)

5.0

-

-

1101±683.1

-

-

-

-

-

-

-

-

-

9AC (pos. control)

80.0

-

-

-

-

-

-

-

-

889±275.7

-

-

-

4NQO (pos. control)

0.25

-

-

-

-

-

-

-

-

-

-

270±66.2

-

B(a)P

5.0

-

1084±236.3

-

-

-

-

-

809±108.4

-

313±41.6

-

354±89.4

2AA (pos. control)

5.0

-

-

-

440±198.6

-

359±127.0

-

-

-

-

-

-

 

 

 

Test substance

1

143

139

36

10

22

23

31

43

10

12

27

32

5

121

147

30

17

20

25

32

50

11

16

20

31

10

127

131

40

13

29

26

38

47

11

21

30

31

50

108

129

34

16

34

28

28

42

7

15

29

34

100

135

134

24

12

22

21

33

54

15

18

31

33

500

119

133

39

16

18

22

38

45

11

8

24

41

1000

103

120

31

9

17

27

31

38

7

7

31

35

5000

65*

101

10*

8

7*

8*

6*

10*

0*

0*

7*

22

-: not tested; *: growth inhibition observed

 

Applicant's summary and conclusion