Alkenes, C11-12, hydroformylation products, low boiling

Genetic toxicity: in vitro

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:

23-Aug-1996 to 07-Oct-1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, and under GLP, with acceptable restrictions. The restrictions were that the strains used did not comply with the current guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(no TA102 or E. coli WP2 uvrA, 2-AA only as positive control with S9)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dodecan-1-ol

EC Number:

203-982-0

EC Name:

Dodecan-1-ol

Cas Number:

112-53-8

IUPAC Name:

dodecan-1-ol

Details on test material:

- Name of test material (as cited in study report): Kalcol 2098 (chemical name: lauryl alcohol)
- Substance type: clear, colourless liquid
- Physical state: liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 3397
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: shielded from light, not necessarily in darkness
- Other:
Date received: 05-Aug-1996

Method

Target gene:

histidine

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

other: histidine deficient

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

other: histidine deficient

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9 .

Test concentrations with justification for top dose:

0.5 (only TA1538 and 1537), 1.5, 5, 15, 50, 150 and 500 (only TA98, 100, 1535) µg/plate (based on a preliminary screening test)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

3 µg/plate (TA100), 5 µg/plate (TA1535), without S9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

80 µg/plate (TA1537), without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylene daimine

Remarks:

5 µg/plate (TA1538), without S9

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

0.2 µg/plate (TA98), without S9

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

1 µg/plate (TA100), 2 µg/plate (TA1535 and TA 1537), 0.5 µg/plate (TA1538 and TA98), with S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar

DURATION
- Exposure duration: 48 hours at 37 deg C

NUMBER OF REPLICATES: triplicates

Evaluation criteria:

Considered positive if there is concentration-related and statistically significant increase in reverse mutation rate in one or more bacterial strains at sub toxic dose levels. To be considered negative, the number of induced revertants should be <2-fold  the number of spontaneous revertants and concentrations should extend to the limits of solubility or toxicity up to a maximum of 5000 µg/plate.

Statistics:

Dunnetts linear regression method.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

50-150 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

50 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: no data
- Precipitation: An oily precipitate was observed at 1500 ug/plate and above in the preliminary toxicity assay, this did not interfere with the scoring of revertant colonies and was not reported when this concentration was tested in the repeat study.
- Other confounding effects: no data

COMPARISON WITH HISTORICAL CONTROL DATA: No

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- With and without metabolic activation: The test material exhibited a visible reduction in background lawn at and above 150 ug/plate in all the strains
tested. Strains TA1538, 1537 and 1535 also showed a reduction in background lawn at 50 ug/plate. This indicates that the material was tested to a 
toxic level.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

STATISTICAL RESULTS: No statistically significant increase in reverse mutation rate at any dose level tested with or without metabolic activation.

Table 1 Experiment 1 Revertants per plate (mean of 3 plates)

Concentrationµg/plate	TA 100		TA 1535		TA 1538		TA 98		TA 1537
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0	113	111	23	18	13	26	27	31	7	9
0.5	N/T	N/T	N/T	N/T	14	N/T	N/T	N/T	7	N/T
1.5	113	111	25	15	15	25	25	30	7	10
5	115	105	21	12	15	24	23	30	7	9
15	111	107	23	12	16	27	27	29	8	10
50	88	92	26	15	9	28	25	25	6	9
150	48	72	24	11	0	11	14	24	0	5
500	0	27	0	7	N/T	0	7	18	N/T	0
Positive control	529	1001	136	232	685	513	185	842	879	309

N/T Not tested

Table 2 Experiment 2 Revertants per plate (mean of 3 plates)

Concentration µg/plate	TA 100		TA 1535		TA 15381		TA 98		TA 1537
	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA
0	86	99	15	13	14	22	21	36	9	11
0.5	96	102	13	N/T	11	2.5	20	N/T	6	N/T
1.5	92	100	13	16	12	22	19	36	8	10
5	93	100	13	15	12	20	20	35	9	9
15	93	101	14	11	15	25	22	30	6	12
50	68	99	12	11	11	21	18	37	7	12
150	25*	70	6*	12	0*	19	9*	28	0*	10
500	N/T	N/T	N/T	8	N/T	N/T	N/T	13	N/T	1
1500	N/T	N/T	N/T	2*	N/T	N/T	N/T	0*	N/T	0*
Positive control	449	1008	293	210	708	442	134	602	1011	337

* Very thin or absent background lawn

N/T Not tested

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In a reliable study, the C12 alcohol Kalcohl 2098 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation. The material was tested to cytotoxic concentrations. The study was performed in compliance with GLP. It is concluded that dodecan-1-ol is negative for the induction of mutations in bacteria under the conditions of the test.