Ethyl chloroformate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Dermal application of small ammounts may be invalid due to high vapor pressure. As no irritating effects have been reported there may have been not any dermal exposure at all. Subcutaneous exposure was only one a week for a relativeley short period of time (22 weeks).

Data source

Reference

Reference Type:

publication

Title:

Carcinogenicity of acylating agents: Chronic bioassays in mice and structure-activity relationships (SARC).

Author:

Van Duurren BL, Melchionne S and Seidman I.

Year:

1987

Bibliographic source:

J Amer Coll Toxicol 6:479-487.

Materials and methods

Principles of method if other than guideline:

Ethyl chloroformate was was applied dermally and subcoutanously. The study included a cancer promotion study with PMA

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl chloroformate

EC Number:

208-778-5

EC Name:

Ethyl chloroformate

Cas Number:

541-41-3

Molecular formula:

C3H5ClO2

IUPAC Name:

ethyl chlorocarbonate

Details on test material:

- Name of test material (as cited): ethyl chloroformate

Test animals

Species:

mouse

Strain:

ICR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, indianapolis, IN, USA
- Age at study initiation: 6-8 weeks
- Weight at study initiation:
- Housing: in groups of 6
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): no data
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

dermal

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: the chemical in 0.1 ml acetone was applied thrice weekly for the duration of the test in the interscapular region. After treatment, the mice were housed in hoods for 2-3 hours before being returned to the animal rooms.
- Time intervals for shavings: regular, no interval given

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 3.0; 4.3; 5.5 mg Ethyl chloroformate/administration
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility, penetration enhancer
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 3.0; 4.3; 5.5 mg Ethyl chloroformate/administration

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

After treatment, the mice were housed in hoods for 2-3 hours before being returned to the animal rooms.

Frequency of treatment:

thrice weekly

Post exposure period:

no

Doses / concentrations

Remarks:

Doses / Concentrations:
3.0; 4.3; 5.5 mg Ethyl chloroformate/administration
Basis:
no data

No. of animals per sex per dose:

50

Control animals:

yes, concurrent vehicle

Details on study design:

no data

Positive control:

no

Examinations

Observations and examinations performed and frequency:

Animals were weighed at 30-60-day intervals, and the average body weights of the treated groups were calculated and compared to controls. Tumor observations were made daily and recorded. Animals that became moribund or died during the treatment period or had large tumor masses were killed by cervical dislocation. All mice were necropsied, and routine sections were taken from the area of administration and also of lung, liver, kidney, spleen, colon, and urinary bladder. All other tissues and organs that appeared clinically abnormal were also taken for histopathology. All tissues were fixed in formalin, blocked in paraffin, view of the large and stained with hematoxylin and eosin for histopathology.

Sacrifice and pathology:

Organs other than the skin were not examined.

Statistics:

yes, but no data concerning the method

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

no effects observed

Details on results:

No skin tumors were observed in groups of 50 animals treated repeatedly on the skin over 18-22 months with 3.0 or 5.5 mg test material. One sarcoma was found in a group of rats treated repeatedly with 4.3 mg test material. The results of this test were not considered to be significant.

An experiment also was conducted in which one dose of test material (5.5 mg) was applied dermally to a group of 50 rats, followed 2 weeks later by repeated dosing with the tumor promoter PMA (3 times weekly until the study was terminated). Whereas 3/30 rat treated with PMA developed skin tumors (2 papilloma and 1 sarcoma), 6/50 rats treated with ethyl chloroformate developed skin tumors (4 papilloma, 2 squamous cell carcinoma). The results of this study were significant at p < 0.05.

An experiment also was conducted in which test material (0.3 or 1.1 mg) was injected subcutaneously once/week over a period of 18-22 weeks. The tumor incidences at each of the concentrations were 1/50 (squamous cell carcinoma) and 0/30, which were not different from the controls [0/30, 2/50 (2 hemangioma, and 0/50]. The results of this test were not considered to be significant.

Effect levels

Dose descriptor:

NOAEL

Effect level:

5.5 other: mg/traetment

Sex:

female

Basis for effect level:

other: skin umors

Remarks on result:

other: Effect type: carcinogenicity (migrated information)