1,1-dimethoxycyclododecane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro: Ames test (OECD 471): negative with S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Sep - 11 Oct 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted 21 July 1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt und Verkehr, Baden-Württemberg, Germany

Type of assay:

bacterial reverse mutation assay

Target gene:

his operon

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

co-factor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254

Test concentrations with justification for top dose:

First experiment:
5; 15; 50; 150; 500; 1500 and 5000 µg/plate with and without metabolic activation

Second experiment:
1,5; 5; 15; 50; 150; 500; 1500 and 5000 µg/plate without metabolic activation
15; 50; 150; 500; 1500 and 5000 µg/plate with metabolic activation

Vehicle / solvent:

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

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

other: 2-aminoanthracene

Remarks:

+S9: 2-AA (0.8µg/plate for TA98, TA100; 0.9µg/plate for TA102, TA1535; 1.7 µg/plate for TA1537); -S9: NaN3 (0.7 µg/plate for TA100, TA1535), 2-NF (2.5 µg/plate for TA98), 9-AA (50 µg/plate for TA1537), Mitomycin C (0.15 µg/plate for TA102)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48–72 h

NUMBER OF REPLICATIONS: 3 replications each in 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: decrease in the number of revertants, clearing or diminution of the background lawn

Statistics:

Mean values and standard deviation were calculated.

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

-S9: at 500 µg/plate; +S9: at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

+S9: at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

-S9: at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

-S9: at 500 µg/plate; +S9: at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

-S9: at 500 µg/plate; +S9: at 1500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation of the test substance was observed on the plates.

Table 1: Test Results of Experiment 1

EXPERIMENT 1
S9-Mix	Without
Test item (µg/plate)	TA 98	TA 100	TA 102	TA 1535	TA 1537
NC	44 ± 4	110 ± 16	269 ± 14	11 ± 5	9 ± 4
Solvent control (ethanol)	34 ± 11	106 ± 7	264 ± 12	12 ± 3	7 ± 2
5	-	-	283 ± 5	-	6 ± 2
15	37 ± 3	97 ± 10	292 ± 29	-	6 ± 1
50	44 ± 8	114 ± 11	248 ± 15	14 ± 6	6 ± 2
150	25 ± 4	109 ± 4	190 ± 10	11 ± 5	7 ± 3
500	33 ± 5	94 ± 3	170 ± 10 (T)	12 ± 7	5 ± 2
1500	34 ± 4	66 ± 5 (T)	-	9 ± 1	-
5000	-	-	-	8 ± 3	-
NaN3 (0.7)	-	491 ± 29	-	411 ± 9	-
2-NF (2.5)	463 ± 107	-	-	-	-
9-AA (50)	-	-	-	-	454 ± 49
Mitomycin C (0.15)	-	-	788 ± 28	-	-
S9-Mix	With
Test item (µg/plate)	TA 98	TA 100	TA 102	TA 1535	TA 1537
NC	38 ± 5	130 ± 16	251 ± 17	12 ± 5	16 ± 2
Solvent control (ethanol)	47 ± 4	113 ±13	255 ± 13	12 ± 4	18 ± 4
5	-	-	262 ± 16	-	-
15	-	108 ± 9	264 ± 16	12 ± 1	16 ± 5
50	52 ± 7	118 ± 13	240 ± 22	11 ± 2	16 ± 2
150	49 ± 4	118 ± 13	241 ± 16	13 ± 12	24 ± 3
500	42 ± 4	97 ± 7	224 ± 8	12 ± 2	20 ± 3
1500	52 ± 4	76 ± 6	-	11 ± 2	12 ± 5
5000	33 ± 4	-	-	-	-
2-AA (0.8)	749 ± 81	613 ± 58	-	-	-
2-AA (0.9)	-	-	378 ± 32	132 ± 30	-
2-AA (1.7)	-	-	-	-	177 ± 8
NC = Negative Control T = bacteriotoxic 2-NF: 2-nitrofluorene; 9-AA: 9-aminoacridine; 2-AA: 2-aminoanthracene; NaN3: sodium azide

Table 2: Test Results of Experiment 2

EXPERIMENT 2
S9-Mix	Without
Test item (µg/plate)	TA 98	TA 100	TA 102	TA 1535	TA 1537
NC	52 ± 8	92 ± 8	214 ± 21	12 ± 3	13 ± 3
Solvent control (ethanol)	47 ± 7	82 ± 5	222 ± 13	10 ± 2	8 ± 2
1.5	-	-	237 ± 8	-	-
5	-	86 ± 14	242 ± 10	-	-
15	-	80 ± 11	253 ± 6	-	9 ± 2
50	52 ± 15	78 ± 8	238 ± 9	10 ± 2	6 ± 2
150	47 ± 5	70 ± 9	205 ± 3	14 ± 3	7 ± 4
500	54 ± 8	59 ± 6 (T)	-	10 ± 4	5 ± 3 (T)
1500	59 ± 6	-	-	9 ± 3	6 ± 2 (T)
5000	33 ± 3 (T)	-	-	11 ± 2	-
NaN3 (0.7)	-	409 ± 18	-	322 ± 16	-
2-NF (2.5)	431 ± 18	-	-	-	-
9-AA (50)	-	-	-	-	228 ± 22
Mitomycin C (0.15)	-	-	605 ± 65	-	228 ± 22
S9-Mix	With
Test item (µg/plate)	TA 98	TA 100	TA 102	TA 1535	TA 1537
NC	48 ± 11	88 ± 15	259 ± 11	19 ± 5	11 ± 2
Solvent control (ethanol)	48 ± 7	97 ± 4	263 ± 15	21 ± 2	15 ± 4
15	-	-	255 ± 21	-	-
50	41 ± 3	103 ± 7	237 ± 13	20 ± 5	14 ± 3
150	51 ± 7	91 ± 10	235 ± 31	17 ± 4	16 ± 4
500	48 ± 5	111 ± 2	214 ± 19	18 ± 3	12 ± 4
1500	56 ± 9	87 ± 1	160 ± 12 (T)	15 ± 3	11 ± 2
5000	33 ± 5	19 ± 3 (T)	-	9 ± 3 (T)	1 ± 2 (T)
2-AA (0.8)	707 ± 23	619 ± 43	-	-	-
2-AA (0.9)	-	-	377 ± 20	133 ± 21	-
2-AA (1.7)	-	-	-	-	194 ± 9
NC = Negative Control T = bacteriotoxic 2-NF: 2-nitrofluorene; 9-AA: 9-aminoacridine; 2-AA: 2-aminoanthracene; NaN3: sodium azide

Conclusions:

Under the experimental conditions described, the test substance was not mutagenic in the Ames test using the Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA102 with and without metabolic activation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Justification for selection of genetic toxicity endpoint
There is only one study available. This study is sufficient to fulfil the standard information requirements set out in Annex VII, 8.4 of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Based on the available data, there is no indication that the substance induces genetic toxicity. Nevertheless, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 can be made, as no information on chromosomal aberration and mutagenicity in mammalian cells/in vivo is available.