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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 based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1981-09-09 to 1991-09-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
limited documentation, incomplete strain selection
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Isopropyl myristate
EC Number:
203-751-4
EC Name:
Isopropyl myristate
Cas Number:
110-27-0
Molecular formula:
C17H34O2
IUPAC Name:
isopropyl myristate
Details on test material:
- Name of test material (as cited in study report): Isopropylmyristate
- Analytical purity: no data

Method

Target gene:
Genes involved in Histidine synthesis
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
other:
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
other:
Metabolic activation:
with and without
Metabolic activation system:
S9-Mix (Aroclor 1254 induced)
Test concentrations with justification for top dose:
0, 4, 20, 100, 500 and 2500 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
water
Negative solvent / vehicle controls:
yes
Remarks:
Acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-Nitro-o-phenylendiamin
Remarks:
TA1537, TA1538 and TA98 without metabolic activation
Untreated negative controls:
yes
Remarks:
water
Negative solvent / vehicle controls:
yes
Remarks:
Acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA1535 and TA100 without metabolic activation
Untreated negative controls:
yes
Remarks:
water
Negative solvent / vehicle controls:
yes
Remarks:
Acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene
Remarks:
All strains with metabolic activation
Evaluation criteria:
Revertant colonies were counted and the means and standard deviations were calculated and compared to the controls.
Statistics:
Means and standard deviations were calculated

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY:
The vehicle acetone with 100 µL/plate had cytotoxic effects on the tester strains TA 100 and TA 1537 with and without metabolic activation. Therefore additional experiments with 50µL acetone/plate with these two strains were performed. These experiments lead to valid results except for TA 1537 without activation. To obtain reliable results and for the comparability of the two series of experiments, the relative numbers of revertants in comparison to the vehicle control were calculated (Table 2).

Any other information on results incl. tables

Table 1: Maximum number of revertants

 

Maximum number of revertants (dose level [µg/mL])

Negative control

Positive control

Treatment

Strain

With S9

Without S9

With S9

Without S9

With S9

Without S9

TA 98

24

20

796

843

25 (2500)

18 (4)

TA 100

150

49

935

375

128 (500)

49 (500)

TA 1535

13

6

145

336

11 (2500)

9 (2500)

TA 1537

13

8

275

--

10 (4)

--

TA 1538

27

16

376

662

20 (100)

17 (500)

Table 2: Maximum relative number of revertants

 

Maximum relative number of revertants (dose level [µg/mL])

Negative control

Positive control

Treatment

Strain

With S9

Without S9

With S9

Without S9

With S9

Without S9

TA 98

1

1

33.6

42.2

1.03 (2500)

0.90 (4)

TA 100

1

1

6.2

7.6

0.85 (500)

0.99 (500)

TA 1535

1

1

11.2

58.9

0.81 (2500)

1.58 (2500)

TA 1537

1

1

21.5

--

0.74 (4)

--

TA 1538

1

1

13.9

40.6

0.72 (100)

1.01 (500)

The results for TA 1537 without S9 -mix were not valid. Although the targets of reverse mutations are different in TA 1537 and TA 98, the possible mutational event in both strains is frameshift. TA 98 is additionally more sensitive to mutations because it carries the R-factor (pKM101) plasmid. The fact that there is no increase in revertants in TA 98 without S9 -mix, gives evidence that there would be no increase of revertants in TA 1537 as well. Therefore it can be concluded that the test substance showed no increase in the number of revertants at any concentration in any tester strain. The test substance is non-mutagenic.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

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