Isopropyl acetate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

EPA OTS 798.5395 (In Vivo Mammalian Cytogenics Tests: Erythrocyte Micronucleus Assay)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley Inc
- Age at study initiation: 8 to 11 weeks
- Assigned to test groups randomly: yes
- Diet: ad libitum):
- Water: ad libitum):
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 72+/- 6 F
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12:12

Route of administration:

intraperitoneal

Vehicle:

0.9% sodium chloride aqueous solution

Details on exposure:

The doses were set following a rangefinder study to determine the MTD.

Duration of treatment / exposure:

Single dose with euthanasia at 24, 48 or 72 hr post injection

Frequency of treatment:

Once

Post exposure period:

24, 48 or 72 hours

Dose / conc.:

350 mg/kg bw/day (actual dose received)

Dose / conc.:

1 173 mg/kg bw/day (actual dose received)

Dose / conc.:

2 500 mg/kg bw/day (actual dose received)

Remarks:

Dosing originally started at 3500mg/kg but was reduced to 2500mg/kg due to excessive mortality and a second trial initiated.

No. of animals per sex per dose:

45; 15 per time interval for sacrifice.

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Justification for choice of positive control(s): Known positive activity in this test.
- Route of administration: i.p.
- Doses / concentrations: 80 mg/kg

Tissues and cell types examined:

Bone marrow cells

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: 35/40 mice at the scheduled top dose of 3500 mg/kg IPA died within 24 hr of injection and the top dose was decreased to 2500 mg/kg

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Bone marrow harvest performed by removal of soft tissue and epiphyses, then flushing with FBS.

DETAILS OF SLIDE PREPARATION: Air dried, fixed in methanol ,stained in May-Grunwald solution followed by Giemsa.

METHOD OF ANALYSIS: scored for micronucleii and PCE/NCE ratio. 1000 PCEs/animal were scored.

OTHER: Normal background frequency of micronucleii in this strain of mouse: 0.4%

Evaluation criteria:

Frequency of micronuclei and ratio of polychromatic to normochromatic erythrocytes (PCE:NCE)

Statistics:

Following square root-arcsine transformation, Tukey's studentized range test was applied to analysis of variance results.

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

Interpretation of results (migrated information): negative
Isopropanol was not genotoxic to mouse bone marrow cells following single i.p. injection at sub-toxic doses up to 2500 mg/kg.

Executive summary:

An in vivo GLP cytogenicity study was performed using isopropanol according to the EPA OTS 798.5395 guideline (“in vivo mammalian cytogenetics tests: erythrocyte micronucleus assay”). Male and female ICR mice were administered single doses of 350, 1173 and 2500mg/kgbw isopropanol i.p. in saline solution. Groups of 15 animals per sex were sacrificed at 24, 48 and 72 hours post injection. Both negative (solvent) and positive (cyclophosphamide, 80mg/kg) were used. Isopropanol did not increase the frequency of micronuclei or the ration of polychromatic to normochromatic (PCE:NCE) erythrocytes and was therefore considered negative in the assay.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl acetate

EC Number:

203-561-1

EC Name:

Isopropyl acetate

Cas Number:

108-21-4

Molecular formula:

C5H10O2

IUPAC Name:

isopropyl acetate

Details on test material:

- Name of test material (as cited in study report): isopropyl acetate

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid