Ethyl chloroacetate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

Remarks:

subcutaneous

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: The subcutaneous route is not relevant and the animals were only administered the substance once a week.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1974

Materials and methods

Principles of method if other than guideline:

Administered by subcutaneous route into female ICR/Ha Swiss mice, ethyl chloroacetate was tested for carcinogenic activity. The mice were given weekly injections in the left flank. The treatments were continued throughout the test. The incidence of sarcomas at the site of injection and tumors at sites distant from the area of administration was tabulated for test and control groups.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl chloroacetate

EC Number:

203-294-0

EC Name:

Ethyl chloroacetate

Cas Number:

105-39-5

Molecular formula:

C4H7ClO2

IUPAC Name:

ethyl 2-chloroacetate

Details on test material:

- Name of test material (as cited in study report): Ethyl chloroacetate
- Source: Eastman Organic Chemicals, Rochester, N.Y.
- Method of purification: Distillation, bp 138-140° C/760 mm.

Test animals

Species:

mouse

Strain:

other: ICR/Ha Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A.R. Schmidt-Sprague-Dawley, Madison, Wisc.
- Age at study initiation: 6-8 weeks old
- Housing: The mice were housed, 10 to a cage, on sterile, hardwood chips (Iso-Dry, Fisher & Son, Bound Brook, N.J.) in stainless-steel cages 11x7x6 inches high.
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24 ºC

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

other: tricaprylin

Details on exposure:

The mice were given injections in the left flank with a 26-gauge, %-inch stainless-steel needIe (Becton, Dickinson & Co., Rutherford, N.J.), mounted on a 1-cc glass tip tubercuIin syringe graduated to 0.01 mL.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

580 days

Frequency of treatment:

Once a week

Post exposure period:

All compounds were used in well-ventilated hoods, and the mice were housed there for at least 3 hours after treatment.

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mg/0.05 mL Tricaprylin
Basis:
nominal conc.

No. of animals per sex per dose:

50 female mice per dose

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The dosages used in all experiments were based on short-term toxicity evaluations (for 4 wk), and the highest possible doses that gave minimal cytotoxic effects were used.

Positive control:

It was used 0.3 mg of ß-propiolactone per 0.05 mL tricaprylin .

Examinations

Observations and examinations performed and frequency:

All animals were examined regularly and the findings were recorded monthly.

BODY WEIGHT: Yes
- Time schedule for examinations: Weighed monthly

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Animals in poor health or with large tumor masses were killed.
Except for the cranial region, animals were completely autopsied at the end of the experiment or at death. Although samples of all tissues and organs
were not taken from each animal on test, the autopsies were done carefully and samples of all abnormalappearing tissues and organs were excised for histopathologic diagnosis. All tissue sections were fixed in 10% formalin, processed, blocked in paraffin, and stained with hematoxylin and eosin for histopathologic examination.

Statistics:

The incidence of sarcomas at the site of injection and tumors at sites distant from the area of administration was tabulated for all test and control groups. Significance values (P) were calculated for the most common distant tumors. In both no-treatment control groups and test groups, the cut-off point for significance was P= 0.05. If a compound had a P value of 0.05, it was considered borderline. P values > 0.05 were considered not significant. Any compound with a P value < 0.05 was considered to have significant tumorigenic activity. All statistical data were computed based on 1 degree of freedom.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Details on results:

They found no significant difference between the incidence of distant tumors in treated animals and the incidence in no-treatment control groups.
One of 50 mice had a local sarcoma in the group given tricaprylin only. No malignant tumors were observed in control group.
The positive control (3-propiolactone) resulted in 28 sarcomas, 4 squamous cell carcinomas and 2 adenocarcinomas of breast origin near the injection site.
Median survival time: 471 days.

Relevance of carcinogenic effects / potential:

They found no significant difference between the incidence of distant tumors in treated animals and the incidence in no-treatment control groups.

Effect levels

1

Dose descriptor:

dose level: 1 mg/0.05 mL tricaprylin

Effect level:

1 other: of 50

Sex:

female

Basis for effect level:

other: p> 0.05

Remarks on result:

other:

Remarks:

Effect type: other: sarcomas (migrated information)

2

Dose descriptor:

dose level: 1 mg/0.05 mL tricaprylin

Effect level:

0 other: of 50

Sex:

female

Basis for effect level:

other: p> 0.05

Remarks on result:

other:

Remarks:

Effect type: other: squamous cell carcinomas (migrated information)

3

Dose descriptor:

dose level: 1 mg/0.05 mL tricaprylin

Effect level:

0 other: of 50

Sex:

female

Basis for effect level:

other: p> 0.05

Remarks on result:

other:

Remarks:

Effect type: other: adenocarcinomas (migrated information)

Applicant's summary and conclusion

Conclusions:

They found no significant difference between the incidence of distant tumors in treated animals and the incidence in no-treatment control groups. On the basis of their findings the authors classified ethyl chloroacetate as non-carcinogenic under the prevailing test conditions.

Executive summary:

Administered by subcutaneous route into female ICR/Ha Swiss mice, ethyl chloroacetate was tested for carcinogenic activity. The dose used was 1 mg/0.05 mL tricaprylin and the mice were given weekly injections in the left flank. The treatments were continued throughout the test. The incidence of sarcomas at the site of injection and tumors at sites distant from the area of administration was tabulated for test and control groups.

One of 50 mice had a local sarcoma in the group given tricaprylin only. No malignant tumors were observed in no treatment group. The positive control (3-propiolactone) resulted in 28 sarcomas, 4 squamous cell carcinomas and 2 adenocarcinomas of breast origin near the injection site.

They found no significant difference between the incidence of distant tumors in treated animals and the incidence in no-treatment control groups (p>0.05). On the basis of their findings the authors classified ethyl chloroacetate as non-carcinogenic under the prevailing test conditions.