Isopropyl benzoate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Isopropyl benzoate is not mutagenic in the Ames assay.

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:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study report according to GLP standards, but documentation incomplete.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Not conducted on all five strains of Bacterial

GLP compliance:

yes

Type of assay:

bacterial gene mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

- Media Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes

Species / strain / cell type:

S. typhimurium TA 98

Details on mammalian cell type (if applicable):

- Type and identity of media:
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Metabolic activation system:

S9 mix, both in the presence and absence of Rat liver derived metabolic activation system

Test concentrations with justification for top dose:

5000-100 micro gram/ plate.
Rationale for maximum concentration selection is Limit test.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Dried DMSO;

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

yes

Remarks:

Without S9 mix

Positive controls:

yes

Remarks:

with S9 mix

Details on test system and experimental conditions:

DURATION: - Preincubation period: Repeat +S9 phase was conducted using a Preincubation assay protocol
- Exposure duration: All plates were assayed after incubation for 3 days
SELECTION AGENT (mutation assays): Ames test
NUMBER OF REPLICATIONS: Two

Evaluation criteria:

Positive gene mutation in TA 98 and TA 100 strains of the bacteria S. Tryphimurium.

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

In TA 100, IPB gave a non mutagenic response.

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

In TA 98, IPB gave a non mutagenic response.

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

not specified

Remarks on result:

other: strain/cell type: S. typhimurium TA 100

Remarks:

Migrated from field 'Test system'.

Bacterial Strain	+S9-mix		-S9-mix Plate Protocol
	Plate Protocol	Pre-incubation Protocol
TA98 TAIOO	negative negative	negative negative	negative negative

Conclusions:

Interpretation of results (migrated information):
negative

Under the limited conditions of this assay (two strains of Salmonella typhimurium), isopropyl benzoate gave a negative (non-mutagenic) response in both the presence and absence of S9 mix for both strains of bacteria (TA 98 and TA 100) tested.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Isopropyl benzoate is not mutagenic in the Ames assay. The metabolite isopropyl alcohol is not mutagenic. Benzoic acid and its salts are not mutagenic in the Ames assay, but have shown positive or inconclusive results in mammalian in vitro mutagenicity assays. In vivo studies have been negative (non-mutagenic). The weight of evidence is that the substance is not mutagenic, as adopted by authoritative bodies such as EFSA, JECFA, SCF and FDA, and expert groups (WHO, OECD SIDS Expert Panel, and the CIR). See SCF, 2002, for discussion of the in vivo studies, including a chromosomal aberration assay in bone marrow cells of Sprague-Dawley rats at doses up to 5000 mg/kg bw/day sodium benzoate, and a dominant lethal test (5000 mg/kg bw/day sodium benzoate) in male Sprague-Dawley rats.

Isopropyl benzoate is part of a category of chemicals, the Alkyl Benzoates, which utilize this data on benzoic acid and sodium benzoate for safety evaluation. The establishment of a benzoates category has been accepted by numerous expert toxicology groups, including the Joint Expert Committee for Food Additives (JECFA), the Scientific Committee on Food (SCF), the European Food Safety Organization (EFSA), the U.S. Food and Drug Administration (FDA), the World Health Organization (WHO), and the OECD High Production Volume Chemicals Programme (OECD HPV). The basis of the large category for all these organizations (EFSA now has a category of 41 substances qualifying as Benzyl Derivative flavours) is a common breakdown product, benzoic acid, which forms rapidly by acidic hydrolysis as well as due to the action of esterase enzymes.

Justification for selection of genetic toxicity endpoint
experimental data

Justification for classification or non-classification

The substances are evaluated as non-mutagenic, and do not meet the criteria for classification and labelling according to Regulation EC No. 1272/2008.