2-chloropropane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1983 followed, reliability scoring based on 1997 guideline.

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-chloropropane

EC Number:

200-858-8

EC Name:

2-chloropropane

Cas Number:

75-29-6

Molecular formula:

C3H7Cl

IUPAC Name:

2-chloropropane

Details on test material:

- Name of test material (as cited in study report): Isopropylchloride (2-chloro-propane)
- Physical state: Liquid (colourless)
- Storage condition of test material: Cool, well-ventilated place

Test animals

Species:

mouse

Strain:

other: BOR:NMRI SPF (Han.)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma Winkelmann, Versuchtierzucht
- Age at study initiation: Adult (about 3 months)
- Weight at study initiation: 32.0 to 40.1 g (males); 29.8 to 38.4 g (females)
- Assigned to test groups randomly: Yes, by lot
- Housing: Collective caging
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 ± 1.5
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil
- Amount of vehicle (if gavage or dermal): 10 mL/kg
- Lot/batch no. (if required): Batch: 2466515
- Manufacturer: Roth GmbH, Karlsruhe

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Not reported.

Duration of treatment / exposure:

Single administration

Frequency of treatment:

Single administration

Post exposure period:

24, 48, or 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

5/sex in control groups and 15/sex in test-article groups (with 5/sex being sacrificed for smear evaluation at each time point)

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Route of administration: intraperitoneal
- Doses / concentrations: 40 mg/kg bw in 10 mL/kg corn oil

Examinations

Tissues and cell types examined:

Bone marrow from femurs.

Details of tissue and slide preparation:

The femurs were removed and the bone marrow was suspended in fetal calf serum. Samples were centrifuged at 1.600 x g, decanted and then one drop of each single suspension was smeared on a slide by means of a second slide.

These preparations were dried, fixed in absolute (99 %) methanol for 5 min. and then allowed to air dry. The slides were stained using a May-Grünwald and Giemsa solution.

From each animal 2 preparations were made. Prior to analysis all the slides were randomized and coded (blind evaluation).

Evaluation criteria:

The test substance is considered to be active if a statistically significant increase in the number of polychromatic erythrocytes with micronuclei in comparison to the control values occurs at any point in time.

Statistics:

One factorial analysis of variance.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 1000, 2500 and 5000 mg/kg bw
- Clinical signs of toxicity in test animals:
Animals treated with 5000 and 2500 mg/kg showed severe ataxia, a distinct writhing-reflex, a lateral body position, sedation and piloerection i.e. 5 mind. p.a. and up to 4 hours p.a., whereby the lower dosed animals only showed slight ataxia, a slight sedation and a slight piloerection at this point of time. Animals treated with 1000 mg/kg were slightly sedated for about 1 hour and showed a very slight piloerection.

Any other information on results incl. tables

A very slightly reduced activity (sedation) and piloerection was noted 1 to 3 hours following administration, but the animals were normal in appearance and behaviour afterwards. No animal died throughout the study.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative