3-chloropropene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

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: - guideline compliant study - non-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

Deviations:

yes

Remarks:

: only one relatively low dose tested

GLP compliance:

no

Type of assay:

Drosophila SLRL assay

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropene

EC Number:

203-457-6

EC Name:

3-chloropropene

Cas Number:

107-05-1

Molecular formula:

C3H5Cl

IUPAC Name:

3-chloroprop-1-ene

Details on test material:

- Name of test material (as cited in study report): 3-chloropropene
- Physical state: clear, colourless liquid
- Analytical purity: 98 %
- Impurities (identity and concentrations): not reported
- Purity test date: not reported
- Lot/batch No.: Batch No. 17835
- Supplier: Aldrich Chemical Company Limited (18 March 1980)
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported, but expected to be stable
- Storage condition of test material: retained in the dark under ambient conditions in the company dispensary until used
- Other:

Test animals

Species:

Drosophila melanogaster

Strain:

other: wild type flies: Oregon K, mutant flies: Müller-5

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not reported
- Age at study initiation: 3 d
- Weight at study initiation: not applicable
- Assigned to test groups randomly: not reported
- Fasting period before study: no
- Housing: in 3 '' x 1 '' glass vials containing 8 mL of feeding medium, stoppered with cotton wool
- Diet (e.g. ad libitum): medium made of maize meal (150g/L) treacle (130 g/L), agar (Sigma, 20g/L), yeast (flaked, 22/L), propionic acid (5 mL/L),
Nipogen (bacteriostatic agent, BDH Limeted; 1 g/L) and boiled before use
- Water (e.g. ad libitum): not applicable
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- not reported

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

no vehicle necessary

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body


GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass vessel
- Method of holding animals in test chamber: not applicable
- Source and rate of air: Compressed air was supplied py means of 2 Broomwade compressors (Type CAR31) fitted with automatic pressure control switches. These supplied filtered, conditioned, oil-free compressed air for subsequent dilution of test atmospheres.
- Method of conditioning air: not reported
- System of generating vapour: The high level atmosphere was produced by bubbling dry, oxygen-free nitrogen (BOC Limited) through a liquid reservoir of 3-chloropropene contained in a glass, gas washing or Drechsel bottle immersed in a temperature controlled water bath at 1 °C. The
nitrogen/3-chloropropene vapour mixture so generated was ducted through 7/16" ID stainless steel piping to a glass mixing vessel and diluted with filtered, compressed air.
- Temperature, humidity, pressure in air chamber: not reported
- Air flow rate: 5 L/min
- Air change rate: not reported
- Treatment of exhaust air: Contaminated air extracted from the exposure chamber was 'scrubbed' using methylated spirits/water treatment. It was then diluted in the building exhaust air before discharging to the external atmosphere.

TEST ATMOSPHERE
- Brief description of analytical method used: The atmospheres within the exposure chambers were analysed by infra-red spectroscopy using Miran-1A Portable Gas Analysers (Foxboro/Wilks Inc). This type of instrument is a single beam, variable wavelength spectrometer, scanning the infra-red spectrum between 2.5 and 14.5 µm. It is equipped with a gas cell having a variable pathlength of between 0.75 and 21.75 m. Samples of the chamber air were continuously pumped (5 l/min) through stainless steel sample lines of 3/8'' ID, to the gas cell of the analyser. The concentration was measured and relayed to a chart recorder (Servoscribe RE 541) to provide a permanent record of the chamber concentrations.
The infra-red gas analyser used to monitor chamber atmospheres of 3-chloropropene were calibrated each day before vapour generation commenced using a closed loop calibration system.
- Samples taken from breathing zone: yes

Duration of treatment / exposure:

7 h per day

Frequency of treatment:

once

Post exposure period:

not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
150 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

10 males per dose in the F0 generation

Control animals:

other: positive controls treated with 0.4 % EMS in sucrose (v/v) for 5 h

Positive control(s):

none

Examinations

Tissues and cell types examined:

not applicable

Details of tissue and slide preparation:

- not applicable

Evaluation criteria:

The untreated control frequency of lethals in the flies used was about 0.2%.True mutation frequencies can only be determined within certain limits because only integral numbers of mutations can be recorded (Würgler et al 1975). These frequencies strongly depend on the sizes of the test groups studied (i.e. the size of individual broods), which are relatively small.
Based upon previous experiences with this test, which is meaningful but insensitive (Rinehart, 1969), it is considered that, in place of a test for statistical significance, it is better to look for a reproducible increase in the frequency of lethals over the historical control value of about 0.1%.
There is, of course, no opportunity for lethals to accumulate. Control values accumulated over the past 1.5 years shown in table 1.
Against this background, the criteria for result assessment were:
(a) a compound giving frequencies below 0.5% in duplicate experiments is considered to show no evidence of mutagenic activity.
(b) a compound giving frequencies greater than 1.0% in the same brood in duplicate experiments is considered to show mutagenic potential.
(c) a compound giving frequencies between 0.5% and 1.0% shows evidence of possibly being mutagenic. Although this evidence is not conclusive, the compound clearly would deserve further study.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

at the used concentrations

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not examined

Additional information on results:

The air control group gave 2 lethals in the F2 generation, both of them being in the first brood of Stock A flies. The frequency in this brood was 0.35%, but no other lethals were detected in a total of 3,598 vials set up and 3,359 vials scored. No lethals were observed in the 562 vials scored
in the F3 qeneration.
Two lethals were also scored in the F2 qeneration from flies exposed to 3-chloropropene. These also were in Brood 1 of Stock A and the frequency was 0.35 %. No other F2 qeneration lethals were scored out of 3,599 vials set up and 3,272 scored. No F3 generation lethals were scored in a total of 1,325 vials.
Flies exposed to a solution of 0.4% EMS in sucrose (v/v) for 5 h gave 14 % lethals in the F2 generation.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: negative, but the results are not fully conclusive as the used exposure levels are relatively low for a subacute exposure.
A Sex-linked Recessive Lethal Test in Drosophila melanogaster was conducted equivalent to OECD Guideline 477 with single exposure (7 h, 150 ppm).
The results are negative but not fully conclusive as the used exposure level is relatively low .

Executive summary:

In the present study (McGregor 1981) the genotoxic potential of 3-chloropropene was tested Sex-linked Recessive Lethal Test in Drosophila melanogaster conducted generally compliant to OECD TG 477 with repeated exposure via the inhalative route (5 d, 7h, 150 ppm).

The results are negative but not fully conclusive as the used exposure levels are relatively low for a subacute exposure. Therefore a classification based on these results is not possible.

In a pretest the toxicity of 3 -chloropropene towards fruit flies was tested and based on this results a exposure regimen of 150 ppm for 7 h via inhalation was chosen even though no toxic effects were reported at this concentration. 3 d old males were exposed in a glass vessel under monitored vapor concentrations and thereafter paired as described in the OECD TG 477. Two breeding stocks of flies were used (A and B)

The air control group gave 2 lethals in the F2 generation, both of them being in the first brood of Stock A flies. The frequency in this brood was 0.35%, but no other lethals were detected in a total of 3,598 vials set up and 3,359 vials scored. No lethals were observed in the 562 vials scored

in the F3 qeneration.

Two lethals were also scored in the F2 qeneration from flies exposed to 3-chloropropene. These also were in Brood 1 of Stock A and the frequency was 0.35 %. No other F2 qeneration lethals were scored out of 3,599 vials set up and 3,272 scored. No F3 generation lethals were scored in a total of 1,325 vials.

Flies exposed to a solution of 0.4% EMS in sucrose (v/v) for 5 h gave 14 % lethals in the F2 generation.

Based on these results it can be concluded that 3 -chloropropene has no genetic effect on the test animals at the used concentrations. The concentration used is only about 1/10 of the acute mammalian LD50. Therefore a final conclusion on the genetic toxicity of 3 -chloropropene in vivo is not possible.