1,1'-(4-chlorobutylidene)bis[4-fluorobenzene]

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Salmonella Mutagenicity Tests: V. Results from the Testing of 311 Chemicals

Author:

Errol Zeiger, Beth Anderson, Steve Haworth, Timothy Lawlor, and Kristien Mortelmans

Year:

1992

Bibliographic source:

Environmental and Molecular Mutagenesis Volume 19, Supplement 21 :2-141 (1992)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Gene mutation toxicity study was performed to evaluate the mutagenic nature of lauryl chloride

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-chlorododecane

Cas Number:

112-52-7

Molecular formula:

C12H25Cl

IUPAC Name:

1-chlorododecane

Details on test material:

- Name of test material: Lauryl chloride
- IUPAC name: 1-chlorododecane
- Molecular formula: C12H25Cl
- Molecular weight: 204.783 g/mol
- Substance type: Organic
- Physical state: No data

Specific details on test material used for the study:

- Name of test material: Lauryl chloride
- IUPAC name: 1-chlorododecane
- Molecular formula: C12H25Cl
- Molecular weight: 204.783 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: Analyzed purity: approx. 98%
- Impurities (identity and concentrations): 2% approx.

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA100, TA1535, TA1537, TA97, TA98

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

The S-9 (9,000 x g supernatant) fractions of Aroclor 1254-induced, male Sprague-Dawley rat and male Syrian hamster livers

Test concentrations with justification for top dose:

0, 100, 333, 1000, 3333 or 10000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was soluble in DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

other: 4-nitro-o-phenylenediamine (TA98 and TA1538; Without S9); 2-aminoanthracene (With S9; all strains)

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: No data

NUMBER OF CELLS EVALUATED: No data

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

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: Plates were machine counted unless precipitate was present which interfered with the count, or the color of the test chemical on the plate reduced the contrast between the colonies and the agar.

Rationale for test conditions:

No data

Evaluation criteria:

The plates were observed for a dose dependent increase in the number of Histidine- independent (his+) colonies.

Evaluations were made at both the individual trial and chemical levels.

Individual trials were judged mutagenic (+), weakly mutagenic (+ W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase in his+ revertants, and the shape of the dose response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of “+ W”, if only a single dose was elevated over the control, or if a weak increase was not dose-related. The distinctions between a questionable response and a nonmutagenic or weakly mutagenic response, and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach two-fold over background for a trial to be judged mutagenic.

A chemical was judged mutagenic (+) or weakly mutagenic (+W) if it produced a reproducible, dose-related response over the solvent control, under a single metabolic activation condition, in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a “+W” response, or if only single doses produced increases in his+ revertants in repeat trials. Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response.

Statistics:

No data

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA100, TA1535, TA1537, TA97, TA98

Metabolic activation:

with and without

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:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: No data
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES: All chemicals were run initially in a toxicity assay to determine the appropriate dose range for the mutagenicity assay. The toxicity assay was performed using TA100. Toxic concentrations were defined as those that produced a decrease in the number of his+ colonies, or a clearing in the density of the background lawn, or both.

COMPARISON WITH HISTORICAL CONTROL DATA: No data

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data

Any other information on results incl. tables

Table: Results for the test chemical Lauryl chloride

Dose (µg/plate)	TA100
	-S9		10% HLI		30% HLI		10% RLI		30% RLI
	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM
0	124	11.2	121	5.7	145	10.7	118	9.0	158	9.2
100	137	8.2	135	10.7	159	6.3	141	4.3	161	4.5
300	116	3.9	120	8.7	143	6.0	143	3.8	141	10.1
1000	112	6.1	138	6.3	144	8.4	146	2.2	148	7.1
3333	93	11.9	135	2.0	143	5.4	138	13.0	155	6.1
10000	93	8.0	96	10.9	129	9.6	137	13.7	169	5.0
Positive control	484	31.2	772	8.7	608	15.7	376	27.1	185	9.5

 

Dose (µg/plate)	TA1535
	-S9		10% HLI		30% HLI		10% RLI		30% RLI
	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM
0	21	2.0	13	1.7	15	0.7	10	0.3	16	1.9
100	25	2.6	8	2.2	13	1.2	9	1.0	15	0.3
300	18	5.0	11	1.5	13	1.5	0	2.0	16	0.6
1000	18	1.2	6	1.5	11	3.0	9	2.6	13	1.0
3333	22	0.7	8	1.9	15	1.2	9	3.0	13	1.5
10000	17	1.2	10	0.3	13	2.7	12	0.9	12	1.2
Positive control	420	6.7	236	7.9	520	5.2	425	34.4	166	7.0

 

Dose (µg/plate)	TA1537
	-S9		30% HLI		30% RLI
	Mean	SEM	Mean	SEM	Mean	SEM
0	9	0.9	17	1.0	15	0.9
100	10	1.8	20	2.2	15	1.0
300	13	1.7	16	1.2	13	0.6
1000	7	0.5	14	1.8	14	0.6
3333	9	1.5	15	1.3	12	1.0
10000	9	1.5	13	1.7	14	2.5
Positive control	246	8.7	50	2.5	46	5.7

 

 

Dose (µg/plate)	TA97
	-S9		10% HLI		30% HLI		10% RLI		30% RLI
	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM
0	155	17.2	170	10.7	175	1.5	198	12.5	178	8.1
100	138	3.3	11	11.7	182	3.8	161	12.0	174	7.2
300	161	5.4	182	12.8	180	9.6	190	6.0	175	8.2
1000	158	3.2	170	5.4	178	7.8	198	5.1	187	4.2
3333	162	2.0	177	7.8	149	4.2	198	2.4	172	7.4
10000	139	17.0	152	13.9	145	2.4	201	5.7	173	10.6
Positive control	737	32.2	496	26.3	350	10.0	382	26.4	330	17.6

 

Dose (µg/plate)	TA98
	-S9		10% HLI		30% HLI		10% RLI		30% RLI
	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM
0	21	3.2	33	5.2	33	2.7	30	4.1	51	3.9
100	20	0.9	30	1.8	33	3.0	31	3.5	40	2.6
300	11	3.9	26	5.4	27	2.3	32	3.8	44	3.8
1000	12	3.2	32	1.0	39	0.9	25	2.7	32	1.7
3333	12	0.6	34	2.4	44	2.0	19	4.8	44	3.0
10000	11	0.3	31	3.8	41	4.0	25	1.2	50	0.6
Positive control	606	11.0	680	24.9	429	38.7	373	24.7	139	13.1

Applicant's summary and conclusion

Conclusions:

Lauryl chloride did not induce mutation in Salmonella typhimurium TA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Executive summary:

Gene mutation toxicity study was performed to determine the mutagenic nature of lauryl chloride. The study was performed usingSalmonella typhimurium strainsTA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in DMSO as solvent and used at dose levels 0, 100, 333, 1000, 3333 or 10000 µg/plate by the preincubation method. The doses were selected on the basis of preliminary dose range finding study and concurrent solvent and positive controls were included in the study. Lauryl chloride did not induce mutation in Salmonella typhimurium TA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.