[2-(1-propoxyethoxy)ethyl]benzene

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation in bacteria (OECD TG 471 - Ames): Not mutagenic.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 March 2000 - 26 May 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine gene

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:

Rat liver S9-mix

Test concentrations with justification for top dose:

50 to 5000 μg per plate in the presence and absence of S9 mix.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Dimethyl sulfoxide (DMSO)
- Justification for choice of solvent/vehicle: according to guidelines

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

other: 2-Aminoanthracene (with metabolic activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: standard plate incorporation
DURATION: Exposure duration: 48h -72h
NUMBER OF REPLICATIONS: The experiment was performed in triplicate and repeated in full after an interval of at least 3 days.
DETERMINATION OF TOXICITY
- Method: Background lawn measurement and reduction in revertant colonies compared to the controls

Statistics:

Estimation of the statistical significance of the difference between the mean number of revertants in the negative controls and the plates at each dosage level was done, using a X2-test (Mohn and Ellenberger,1977).

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 1500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium, other: TA98, TA100, TA102 and TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 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 was observed

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%): A historical overview of the revertant frequencies of the strains used in the Freiburger Labor fur Mutagenitätsprüfung for the years 1998 to 2000.
Mix: -S9 +S9 -S9 +S9
strain: spontaneous /solvent cont./ spontaneous/ solvent cont
TA1535: 31±11 (13/58) 30±11 (10/62) 19±6 (9/27) 18±6 (9/28)
TA1537: 11±4 (5/20) 11±4 (6/21) 16±5 (9/29) 16±5 (9/29)
TA98: 30±8 (18/47) 29±8 (19/50) 40±10 (21/63) 38±9 (23/62)
TA100: 150±35 (89/226) 138±29 (94/205) 139±38 (88/238) 133±38 (79/222)
TA102: 280±37 (218/359) 269±38 (163/337) 306±45 (237/400) 298±46 (207/404)

The historical data of positive controls are given in the form: strain, mutagen (concentration of mutagen in μg/plate), mean of revertants per plate (minimum/maximum). The data of test without S9 are: TA1535, NaN3 ( 0.7), 513±130 (242/688); TA1537, 9-AA (50), 278±97 (131/529); TA98, 2-NF (2.5), 353±113 (190/632); TA100, NaN3 ( 0.7), 427±90 (312/665); TA102, Mitmomycin C (0.15) 820±151 (577/1061). The data of the tests with lot KH3799 of S9 are: TA1535, 2-AA (1.5), 547±205 (310/1118); TA1537, 2-AA (1.5), 299±157 (100/543); TA98, 2-AA (0.7), 919±458 (319/2243); TA100, 2-AA (0.7), 854±336 (402/1955); TA102, 2-AA (1.5), 1116±337 (610/1799). Additional data of the tests with lot KH3799 of S9 are: TA100, B(a)P (5.0), 869±100 (736/976)

ADDITIONAL INFORMATION ON TOXICITY:
In the presence and absence of S9-mix Resedafol / Corps 302 was toxic towards the strains TA1535 at 1500 µg/plate and towards the strains TA98, TA100, TA102, and TA1537 at 5000 μg/plate.

The number of spontaneous revertants observed using each of the five strains was close to those previously established in the laboratory and was within the range obtained by Ames et al. (1975) as well as reported by De Serres and Shelby (1979). The results with the positive control substances confirmed the known reversion properties and specificity of the tester strains as well as the fall activity of the metabolizing system.

Conclusions:

Under the conditions of this study, Hyacinth body #3 was determined to be not mutagenic.

Executive summary:

The mutagenic activity of Hyacinth body #3 was evaluated in Ames test performed in accordance with OECD 471 guideline and according to GLP principles, therefore a Klimisch 1 rating was assigned. The test was performed as a standard plate incorporation assay, both in the absence and presence of S9-mix up to and including 5000 μg/plate. Toxicity, as evidenced by a decrease in the number of revertants and background lawn, was observed. In the presence and absence of S9-mix, Hyacinth body #3 was toxic towards the strains TA1535 at 1500 µg/plate and towards the strains TA98, TA100, TA102, and TA1537 at 5000 μg/plate. No precipitation was observed at any of the concentrations. Adequate negative and positive controls were included. The substance did not induce a significant dose-related increase of the number of revertant (His+) colonies in any of the five S. typhimurium tester strains (TA1535, TA1537, TA98, TA100 TA102), both in the absence and presence of S9 -metabolic activation. These results were confirmed in an independently repeated experiment. Based on the results of this study, it is concluded that Hyacinth body #3 is not mutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

The mutagenic activity of Hyacinth body #3 was evaluated in Ames test performed in accordance with OECD 471 guideline and according to GLP principles, therefore a Klimisch 1 rating was assigned. The test was performed as a standard plate incorporation assay, both in the absence and presence of S9-mix up to and including 5000 μg/plate. Toxicity, as evidenced by a decrease in the number of revertants and background lawn, was observed. In the presence and absence of S9-mix, Hyacinth body #3 was toxic towards the strains TA1535 at 1500 µg/plate and towards the strains TA98, TA100, TA102, and TA1537 at 5000 μg/plate. No precipitation was observed at any of the concentrations. Adequate negative and positive controls were included. The substance did not induce a significant dose-related increase of the number of revertant (His+) colonies in any of the five S. typhimurium tester strains (TA1535, TA1537, TA98, TA100 TA102), both in the absence and presence of S9 -metabolic activation. These results were confirmed in an independently repeated experiment. Based on the results of this study, it is concluded that Hyacinth body #3 is not mutagenic.

Justification for classification or non-classification

Based on the available data, Hyacinth body #3 was determined to be not mutagenic and does not need to be classified for mutagenicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC) and its updates.