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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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

Constituent 1
Chemical structure
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.