Oxydipropanol

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-compliant study, available as unpublished report, performed as a part of carcinogenicity study, minor restrictions in design and reporting, but otherwise adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Principles of method if other than guideline:

The genetic toxicity of dipropylene glycol was assessed by testing the ability of the chemical to induce mutations in various strains of Salmonella typhimurium.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Oxydipropanol

EC Number:

246-770-3

EC Name:

Oxydipropanol

Cas Number:

25265-71-8

Molecular formula:

C6H14O3

IUPAC Name:

1,1-Oxydi-2-Propanol

Details on test material:

- Name of test material (as cited in study report): dipropylene glycol
- Supplier: Radian Corporation (Austin, TX).

Method

Target gene:

His

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

rat or hamster liver S9

Test concentrations with justification for top dose:

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

Vehicle / solvent:

None

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100 and TA1535, -S9

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA97, -S9

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine

Remarks:

TA98, -S9

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

all strains, + S9

Details on test system and experimental conditions:

Dipropylene glycol was incubated with the Salmonella typhimurium tester strains TA97, TA98, TA100, and TA1535 either in buffer or S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver) for 20 minutes at 37° C. Top agar
supplemented with L-histidine and d-biotin was added, and the contents of the tubes were mixed and poured onto the surfaces of minimal glucose agar plates. Histidine-independent mutant colonies arising on these plates were counted following incubation for 2 days at 37° C.
Each trial consisted of triplicate plates of concurrent positive and negative controls and five doses of dipropylene glycol. In the absence of toxicity, 10,000 µg/plate was selected as the high dose. All trials were repeated at the same or higher S9 percentage.

Evaluation criteria:

In this assay, a positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following chemical treatment. There is no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.

Statistics:

Not applied.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not applicable

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY: In the absence of toxicity, 10,000 µg/plate was selected as the high dose.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Mutagenicity of dipropylene glycol in Salmonella typhimurium strains TA100, TA1535, TA97

Strain	Dose (µg/plate)	Revertants per plate
		- S9		+ hamster S9		+ hamster S9
		Trial 1	Trial 2	10%	30%	10%	30%
TA100	0 100 333 1000 3333 10000   Trial summary   Positive control	165 ± 1.7 156 ± 3.5 170 ± 5.8 162 ± 4.0 178 ± 3.1 177 ± 6.2   Negative     343 ± 17.0	112 ± 9.7 99 ± 4.1 115 ± 7.1 118 ± 3.9 116 ± 5.0 121 ± 8.8   Negative     430 ± 3.6	121 ± 2.4 128 ± 5.4 132 ± 4.6 122 ± 8.5 125 ± 3.7 109 ± 5.5   Negative     335 ± 3.6	159 ± 4.2 161 ± 11.3 173 ± 7.4 193 ± 9.8 158 ± 8.3 170 ± 4.9   Negative     446 ± 7.8	112 ± 10.1 123 ± 2.2 141 ± 2.6 111 ± 7.7 121 ± 1.2 103 ± 8.5   Negative     963 ± 7.3	191 ± 11.0 185 ± 14.0 182 ± 13.2 170 ± 7.5 202 ± 24.2 190 ± 7.0   Negative     950 ± 12.2
TA1535	0 100 333 1000 3333 10000   Trial summary   Positive control	6 ± 3.0 9 ± 0.9 10 ± 0.7 13 ± 2.5 11 ± 1.3 13 ± 1.2   Negative     206 ± 12.1	8 ± 1.3 10 ± 0.6 12 ± 1.8 11 ± 2.6 9 ± 1.3 10 ± 1.3   Negative     296 ± 4.7	10 ± 2.2 12 ± 1.3 9 ± 0.6 12 ± 2.8 13 ± 2.7 12 ± 2.4   Negative     62 ± 4.5	17 ± 1.0 14 ± 1.0 22 ± 3.1 15 ± 2.0 20 ± 1.5 21 ± 3.6   Negative     99 ± 18.6	10 ± 0.9 12 ± 2.2 11 ± 1.2 10 ± 0.7 12 ± 0.6 9 ± 2.1   Negative     190 ± 15.4	17 ± 3.2 17 ± 1.3 19 ± 2.8 19 ± 3.5 16 ± 2.0 16 ± 1.5   Negative     950± 12.2
TA97	0 100 333 1000 3333 10000   Trial summary   Positive control	153± 11.7 173 ± 4.4 156 ± 6.7 157 ± 1.5 171 ± 19.1 179 ± 14.2   Negative     972 ± 62.5	95± 1.9 92 ± 7.3 91 ± 5.7 93 ± 6.4 98 ± 3.5 98 ± 12.1   Negative     457 ± 56.2	193± 5.3 204 ± 2.5 204 ± 10.1 208 ± 15.0 179 ± 10.6 196 ± 9.7   Negative     1818 ± 28.2	195 ± 5.2 217 ± 3.1 205 ± 9.6 212 ± 10.1 216 ± 2.2 197 ± 7.0   Negative     921 ± 85.2	193± 3.0 201 ± 12.2 186 ± 6.0 185 ± 2.0 204 ± 7.6 188 ± 5.6   Negative     1562± 152.5	239± 1.5 219 ±.13.9 244 ± 12.4 236 ± 15.2 226 ± 5.4 240 ± 11.6   Negative     564 ± 14.6

Table 2. Mutagenicity of dipropylene glycol in Salmonella typhimurium strain TA98.

Strain	Dose (µg/plate)	Revertants per plate
		- S9		+ hamster S9			+ hamster S9
		Trial 1	Trial 2	10%	10%	30%	10%	30%
TA98	0 100 333 1000 3333 10000   Trial summary   Positive control	19 ± 2.6 22 ± 1.9 17 ± 2.7 17 ± 2.3 22 ± 1.5 19 ± 1.2   Negative     435 ± 4.2	20 ± 3.9 23 ± 0.3 19 ± 1.5 15 ± 1.5 21 ± 1.7 19 ± 2.6   Negative     318 ± 2.3	19 ± 5.8 18 ± 2.6 18 ±.4.3 28 ± 4.1 28 ± 0.9 32 ± 4.7   Negative     258 ± 9.1	17 ± 0.3 18 ± 3.5 17 ± 2.6 13 ± 1.3 16 ± 0.9 13 ± 3.8   Negative     377 ± 8.5	28 ± 2.4 30 ± 3.5 27 ± 5.2 26 ± 1.5 19 ± 2.7 20 ± 5.2   Negative     361 ± 9.9	33 ± 2.2 24 ± 4.2 19 v 0.9 26 ± 3.4 22 ± 3.2 27 ± 3.0   Negative     206 ± 2.3	18 ± 1.7 26 ± 1.7 24 ± 0.0 26 ± 0.7 25 ± 3.2 21 ± 1.8   Negative     407 ± 22.9