Tricyclodecanedimethanol

Genetic toxicity: in vitro

Administrative data

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:

1992-01-14 until 1992-02-17

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

Cited as Directive 84/449/EEC, B.14

Principles of method if other than guideline:

EU method B.13/14 is equivalent to OECD test guideline 471 (Bacterial Revers Mutation Test).

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tricyclodecanedimethanol

EC Number:

248-096-5

EC Name:

Tricyclodecanedimethanol

Cas Number:

26896-48-0

Molecular formula:

C12H20O2

IUPAC Name:

[3-(hydroxymethyl)tricyclo[5.2.1.0²,⁶]decan-8-yl]methanol

Details on test material:

- Name of test material (as cited in study report): Dicidol, Tricyclodecandimethanol, TCD Alkohol DM
- Analytical purity: 98.5 % (GC analysis)
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Purity test date: no data
- Lot/batch No.: A15IVTA055
- Stability under test conditions: stable
- Storage condition of test material: no data

Method

Target gene:

His‾

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA1538

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from Aroclor 1254 induced male rat liver

Test concentrations with justification for top dose:

Main test (plate incorporation) (study number 92/2.1)
8, 40, 200, 1000, and 5000 µg/plate

Preincubation test (study number 92/2.2)
62.5, 125, 250, 500, and 1000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO (plate incorporation test: 50 g/L; preincubation test 20: g/L)
- Justification for choice of solvent/vehicle: no data

Controls

Untreated negative controls:

yes

Remarks:

water

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: without S9-mix: nitrofluorene (TA98, TA1538), sodium azide (TA100, TA1535), aminoacridine (TA1537)

Remarks:

The efficacy of the S9-mix was tested in an assay using the bacterial strain Salmonella Typhimurium TA100 with 2-aminoanthracene as positive control substance.

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation and preincubation

DURATION
- Preincubation period: 30 min at 30 ± 1°C
- Exposure duration: 96 hours at 37°C
- Expression time (cells in growth medium): 96 hours

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth (thinning of the background lawn)

Evaluation criteria:

no data

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

At concentrations of 1000 and 5000 µg/plate.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

At concentrations of 1000 and 5000 µg/plate.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Bacterial Gene Mutation Assay (Plate Incorporation Results - Main Test, Study Number 92/2.1)

 

Dose/Plate (µg/plate)	S9-mix	Revertants (mean of 3 plates ± SD)
		TA98	TA100	TA1535	TA1537	TA1538
neg. control (water)	-	27 ± 4	122 ± 4	10 ± 1	8 ± 4	22 ± 4
Solvent (DMSO)	-	22 * 3	119 ± 16	9 ± 3	7 ± 3	28 ± 3
8	-	26 ± 3	111 ±12	13 ±3	6 ± 2	30 ± 4
40	-	24 ± 7	100 ± 16	7 ± 2	5 ± 4	21 ± 7
200	-	27 ± 3	90 ± 10	11 ±5	5 ± 2	17 ± 5
1000	-	14 ± 5	82 ± 5	7 ± 3 (B)	2 ± 2 (B)	22 ± 4
5000	-	20 ±1	80 ± 6	(A)	(A)	14 ± 4
pos.control	-	206 ± 17	428 ± 14	394 ±25	162 ± 95	102 ± 13
neg. control (water)	+	39 ± 11	124 ± 10	18 ± 3	22 ± 9	45 ± 8
Solvent (DMSO)	+	41 ± 6	103 ± 19	19 ± 10	20 ± 1	46 ± 6
8	+	50 ± 3	93 ± 9	19 ± 3	20 ± 4	42 ± 3
40	+	51 ± 2	89 ± 18	19 ± 9	21 ± 4	45 ± 5
200	+	46 ± 4	107 ± 20	18 ± 4	20 ± 2	45 ± 14
1000	+	46 ± 4	91 ± 9	12 ± 5 (B)	25 ± 5	37 ± 2
5000	+	34 ± 4	80 ± 10	4 ± 3 (A)	8 ± 9 (B)	32 ± 9
Aminoanthracene 10	+	n.t.	1873 ± 225	n.t.	n.t..	n.t.

 

n.t.:  not tested

pos. controls (-S9): TA98, TA1538: Nitrofluorene 2.5 µg/plate

TA100, TA1535: Sodium Azide 2.5 µg/plate

TA1537: Aminoacridine 50 µg/plate

A: Complete clearing of the background lawn

B: Background lawn reduced

 

 Bacterial Gene Mutation Assay (Preincubation Test Results, Study Number 92/2.2)

 

Dose/Plate (µg/plate)	S9-mix	Revertants (mean of 3 plates ± SD)
		TA98	TA100	TA1535	TA1537	TA1538
neg. control (water)	-	25 ± 3	120 ± 3	12 ± 4	14 ± 7	21 ± 4
Solvent (DMSO)	-	23 ± 6	91 ± 6	11 ± 2	16 ± 2	24 ± 7
62.5	-	25 ± 4	108 ± 9	9 ± 1	10 ± 5	21 ± 2
125	-	30 ± 2	99 ± 11	10 ± 3	16 ± 5	32 ± 4
250	-	25 ± 6	116 ± 17	15 ± 1	10 ± 3	22 ± 5
500	-	26 ± 3	92 ± 5	12 ± 3	17 ± 5	22 ± 3
1000	-	20 ± 8	97 ± 11	10 ± 1	19 ± 12	21 ± 10
pos.control	-	160 ± 10	534 ± 28	434 ± 21	73 ± 4	86 ± 6
neg. control (water)	+	48 ± 5	130 ± 2	13 ± 5	11 ± 2	18 ± 3
Solvent (DMSO)	+	46 ± 6	119 ± 21	14 ± 5	12 ± 4	23 ± 4
62.5	+	47 ± 7	96 ±6	20 ± 6	17 ± 2	21 ± 4
125	+	48 ± 3	115 ± 6	16 ± 9	6 ± 2	23 ± 3
250	+	47 ± 11	111 ± 19	14 ± 6	15 ± 4	23 ± 8
500	+	45 ± 3	114 ± 9	12 ± 6	13 ± 2	23 ± 3
1000	+	50 ± 5	121 ± 6	14 ± 8	18 ± 3	22 ± 4
Aminoanthracene 10	+	n.t.	2330 ± 157	n.t.	n.t.	n.t.

 

n.t.: not tested

pos. controls (-S9): TA98, TA153: Nitrofluorene 2.5 µg/plate

TA100, TA1535 Sodium Azide 2.5 µg/plate

TA1537: Aminoacridine 50 µg/plate

A: Complete clearing of the background lawn

B: Background lawn reduced

 

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metobolic activiation

Under test conditions TCD Alkohl DM (Dicidol) showed no mutagenic activity in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, and TA1537, and TA1538 with or without metabolic activation.
According to OECD 471 TCD Alcohol DM is not mutagenic to Salmonella typhimurium.

Executive summary:

In a reverse gene mutation assay in bacteria, strains of S. typhimurium (TA98, TA100, TA1535, TA1537 and TA1538) were exposed to octahydro-4,7-methano-1H-indenedimethanol (98.5%) (TCD Alcohol DM; Dicidol) in DMSO at concentrations of 8, 40, 200, 1000, and 5000 µg/plate (plate incorporation assay) and 62.5, 125, 250, 500, and 1000 µg/plate (pre-incubation assay) in the presence and absence of mammalian metabolic activation (S9 mix from Aroclor induced male rat liver). 

 

Octahydro-4,7-methano-1H-indenedimethanol (TCD Alcohol DM) was tested up to a limit concentration of 5000 µg/plate and showed cytotoxicity (thinning of background lawn) at concentrations of 1000 and 5000 µg/plate. Negative controls did not show a responce and positive controls induced the appropriate responces in the corresponding strains. Octahydro-4,7-methano-1H-indenedimethanol (TCD Alcohol DM) did not increase the number of revertants in any of the test strains. There was no evidence of induced mutant colonies over background (Huels AG, 1992).

This study is classified as acceptable. Although a pre-guideline study, it satisfies the requirement of Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.