Ethyl trichloroacetate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The study was not a regulatory study type and therefore not adequate and relevant for classification of repeated dose toxicity. The study only contained few details, by which it is nog assignable.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1976

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl trichloroacetate

EC Number:

208-212-7

EC Name:

Ethyl trichloroacetate

Cas Number:

515-84-4

Molecular formula:

C4H5Cl3O2

IUPAC Name:

ethyl 2,2,2-trichloroacetate

Details on test material:

- Name of test material (as cited in study report): Ethyl trichloroacetate
- Substance type: Organic monoconstituent substance

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

- Source: bred by the Physiology Department, University of Queensland
- Weight at study initiation: 80-100 g
- Diet (e.g. ad libitum): Ad libitum; the choline deficient diet was that of Kratzing and Windrum (1959); the choline supplemented diet differed only in containing 0.20 g choline /100 g of diet.
- Water (e.g. ad libitum): Ad libitum

Administration / exposure

Route of administration:

subcutaneous

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 or 21 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1036 mg/kg bw

Control animals:

yes, concurrent no treatment

Details on study design:

For the investigation of the long and short-term prophylactic action of ethyl trichloracetate, 12 rats were divided into four equal groups. Two groups were fed the deficient diet and two the complete diet. Half of the deficient group and half of the supplemented group were injected subcutaneously with ethyltrichloracetate ( 0.075 ml/100g).
In the investigation into the effects of the ester on rats with an established choline deflciency, 28 rats were fed the choline deficientdiet and 12 rats the choline supplemented diet.

Examinations

Observations and examinations performed and frequency:

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: On the third day of the experiment, after 18 h fasting, blood samples were obtained from a tail vein. At the end of the experimental period they were obtained by cardiac puncture again after an 18 h fast. All blood samples had 5 mg/mL EDTA added.
- Animals fasted: Yes
- Parameters: Plasma β-lipoproteins (very low density lipoproteins, VLDL and low density lipoproteins, LDL) were assayed by the method of Dangerfield and Faulkner (1964).

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
- The rats were killed, livers were removed immediately and 1.0 g portions were homogenized in 10 mL 0.9% NaCl. Both plasma and hepatic lipids were extracted by the method of Folch, Lees and Sloane-Stanley (1957) and fractionated on Silica Gel G thin layer plates using light petroleum BP 40°-60°; diethyl ether; acetic acid (80:20;1 (v/v/v). Lipids were detected by means of iodine vapour and quantitated using the method of Amenta (1964) using reference samples obtained from the Hormel institute as standards.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

increased plasma β-lipoprotein and triglyceride levels and transient depression in plasma phospholipid after short term treatment; raised hepatic phospholipid after continued treatment

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

drop of nearly 30% in liver triglyceride and significant increases in hepatic phospholipid aftre short-term treatment; rises of about 40% of liver triglyceride and 15% in hepatic phospholipid content after long-term treatment.

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

Rats maintained on a choline deficient diet and treated with subcutaneous doses of ethyl trichloroacetate responded by increasing plasma β-lipoprotein and plasma triglyceride levels while excess triglyceride was being removed from the liver. There was a transient depression in plasma phospholipid at the beginning of the treatment. Continued administration of ethyl trichloroacetate raised plasma triglyceride in choline depleted rats and raised hepatic phospholipid concentration in both choline deficient and supplemented rats.
These changes in plasma lipids are accompanied by a drop of nearly 30% in liver triglyceride after four doses of ethyl trichloracetate, andl significant
increases in hepatic phospholipid. The administration of the ester to choline supplemented rats caused rises of about 40% in the level of liver triglyceride and 15% in hepatic phospholipid content.

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 1 036 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

Rats maintained on a choline deficient diet and treated with subcutaneous doses of ethyl trichloroacetate responded by increasing plasma β-lipoprotein and plasma triglyceride levels while excess triglyceride was being removed from the liver. There was a transient depression in plasma phospholipid at the beginning of the treatment. Continued administration of ethyl trichloroacetate raised plasma triglyceride in choline depleted rats and raised hepatic phospholipid concentration in both choline deficient and supplemented rats.
It is suggested that the lipotropic action of ethyl trichloroacetate occurs through hepatic triglyceride being removed by the altered plasma lipids and not by inhibition of hepatic triglyceride synthesis.