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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
Deviations:
no
Principles of method if other than guideline:
Reverse mutation; increase of histidine independent mutants
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Source: Wako Pure Chemcials Industries, Osaka,, Japan
- Purity 2-EH: 98%

Method

Species / strain
Species / strain / cell type:
other: bacteria. S. typhimurium TA98, TA100, TA1535, TA1537; TA1538; E. coli (WP2uvrA)
Additional strain / cell type characteristics:
other:
Metabolic activation:
with and without
Test concentrations with justification for top dose:
0, 1, 5, 10, 50, 100, 500, 1000 µg/plate
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; preincubation;


DURATION
- Preincubation period: 20 min
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent): 48 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 48 hours


SELECTION AGENT (mutation assays): histidine deficiency
SPINDLE INHIBITOR (cytogenetic assays): n.a.
STAIN (for cytogenetic assays): n.a.


NUMBER OF REPLICATIONS: 2


NUMBER OF CELLS EVALUATED: n.a.


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: no data


OTHER EXAMINATIONS:
- Determination of polyploidy: no
- Determination of endoreplication: no
Evaluation criteria:
no data
Statistics:
no data

Results and discussion

Test results
Species / strain:
other: S. typhimurium and E.coli
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS

ADDITIONAL INFORMATION ON CYTOTOXICITY: growth inhibition was noted in all test strains except TA1537 at 500 and 1000 µg/plate
Remarks on result:
other: other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538; E. coli (WP2 uvrA)
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Except for TA 1537 toxicity was observed at doses of 500 and 1000 µg/plate in
all tester strains.
   
Mean number of revertants:
Dose (µg/plate)
TA100
TA1535
E. coli
WP uvrA
TA98
-S9
+S9
-S9
+S9
-S9
+S9
-S9
+S9
0 water
149
161
28
15
32
33
29
39
0 DMSO
150
154
30
15
30
34
32
42
1
144
170
39
23
32
31
24
44
5
166
171
23
19
30
26
33
61
10
161
149
26
18
27
31
29
48
50
155
147
33
13
26
33
28
57
100
133
151
19
14
28
33
37
51
500
0*
0*
0*
0*
0*
0*
0*
0*
1000
0*
0*
0*
0*
0*
0*
0*
0*
Positive control
501
1084
1101
440
1082
359
278
809
 

    
 
 
Dose (µg/plate)
TA1537
TA1538
-S9
+S9
-S9
+S9
0 water
16
21
21
28
0 DMSO
18
22
22
28
1
13
36
25
24
5
11
28
33
30
10
15
23
29
25
50
16
30
25
30
100
12
26
18
30
500
12
39
0*
0*
1000
16
28
0*
0*
Positive control
889
313
270
354
 0* = growth inhibition 

Applicant's summary and conclusion

Conclusions:
2-EH was not mutagenic in Salmonella typhimurium and E. coli with and without metabolic activation.
Executive summary:

The mutagenicity of 2 -EH was tested in bacterial test sytems (S. tyhimurium TA98, TA100, TA1535, TA1537, TA1538, and E. coli WP2 uvrA) according to OECD TG 471 and TG 472 both with and without metabolic activation in a dose range from 1 to 1000 µg/plate (Shimizu et al., 1985). 2 -EH did not increase the number of revertants in any of the test strains. Growth inhibition was seen at 500 and 1000 µg/plate. The negative and positive controls performed as expected. Therefore, 2 -EH was not mutagenic in baterial test systems in-vitro.