Chloroacetaldehyde

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Only male rats tested.

Data source

Reference

Reference Type:

publication

Title:

Analysis of DNA Strand Breaks Induced in Rodent Liver In Vivo, Hepatocytes in Primary Culture, and a Human Cell Line by Chlorinated Acetic Acids and Chlorinated Acetaldehydes

Author:

Lina W. Chang, F.B. Daniel, Anthony B. DeAngelo

Year:

1992

Bibliographic source:

Environmental and Molecular Mutagenesis 20, 277-288, 1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Single oral dose in distilledwater, 4 h after treatment sacrifice by decapitation.
Dosage: 1/4 - 1/3 of the LD50 based on earlier studies demonstrating biological activity.
Control animals: vehicle only.
1.5 g of the superior-anterior lobe of the liver was removed and analyzed.
An alkaline unwinding assay was used to quantitate the induction of DNA strand breaks:
DAUA = DNA Alkaline Unwinding Assay; estimates the extent of DNA damage (strand breaks) via the assessment of the percentage of DNA remaining double stranded after alkaline unwinding.

GLP compliance:

not specified

Type of assay:

other: DNA strand breaks

Test material

Test material information

Constituent 1

Reference substance name:

Chloroacetaldehyde

EC Number:

203-472-8

EC Name:

Chloroacetaldehyde

Cas Number:

107-20-0

Molecular formula:

C2H3ClO

IUPAC Name:

2-chloroacetaldehyde

Test material form:

other: solution in water

Details on test material:

CAA was purchased from Sigma Chemical Co. (St. Louis, MO)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Male Fischer 344 rats (250-300 g) were purchased from Charles River (Wilmington, MA).
Animals were quarantined for two weeks, food and water ad libitum, 12-hr light-dark-cycle, 22 +/- 2°C, 40-60% humidity.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

single oral dose

Duration of treatment / exposure:

single treatment

Frequency of treatment:

single treatment

Post exposure period:

4 h

Doses / concentrations

Remarks:

Doses / Concentrations:
5 mmol/kg
Basis:
nominal conc.

No. of animals per sex per dose:

No data, animals receiving high doses of 5-10 mmol/kg did not survive.
Highest dose tested: 5 mmol/kg

Control animals:

yes, concurrent vehicle

Positive control(s):

Positive control: N-nitroso-diethylamine (DENA)

Examinations

Tissues and cell types examined:

liver: 1.5 g of the superior-anterior lobe of the liver was removed and analyzed.

Details of tissue and slide preparation:

The liver was removed after decapitation, rinsed, placed in cold modified SBSS and pressed trough a stainless steel tissue press to remove connective tissue. The disrupted livers were mixed with SBSS and filtered. The suspended tissue was centrifuged, resuspended in cold PBS/EDTA and assayed in the DAUA.

Evaluation criteria:

DAUA time: 45 - 60 min. Single and double stranded DNA were separated on a hydroxyapatite column at 60°C. Hoechst dye 33258 was added and the amount of DNA in each fraction was determined fluorimetrically using a Shimadzu RF-5000U set at Ex 350 nm and Em 465 nm. The fraction F of double strand DNA remaining was calculated. A decreasing F value indicates an increase in DNA strand breakage.

Statistics:

The data were analyzed for statistical significance by use of the Dunnett`s test for multiple comparison of treatment means with a control mean.
The level of significance was set at alpha < 0.05.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

high doses: animals died

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

CAA was toxic at higher doses (5-10 mmol/kg) and the rats did not survive.
The positive control (DENA) induced significant levels of DNA damage.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
CAA did not produce detectable DNA damage in vivo in the livers of male F344 rats killed 4 h after a single gavage treatment of the highest dose not causing death (5 mmol/kg). The F-value was not significantly reduced compared with the positive control.

Executive summary:

CAA did not produce detectable DNA damage in vivo in the livers of male F344 rats killed 4 h after a single gavage treatment of the highest dose not causing death (5 mmol/kg). The F-value was not significantly reduced compared with the positive control.