1,1,2-trichloroethane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, performed in a way similar to OCDE 417 Guidelines, with acceptable restrictions.

Data source

Reference

Reference Type:

publication

Title:

Metabolism of 1,1,2-trichloroethane 1,2-14C in the Mouse

Author:

Yllner S

Year:

1971

Bibliographic source:

Acta Pharmacol. et Toxicol. 1971, 30, 248-256

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

Only single administration was tested; justification of dose spacing is not reported

Principles of method if other than guideline:

The labelled trichloroethane was administered by intraperitoneal injection as a 10% solution in olive oil. The animals were placed in chamber with flow of dry air free of carbon dioxide. The elimination of radioactivity was followed for 3 days (urine, faeces and volatile metabolite). Isotope dilution analysis was performed for identification and determination of metabolites.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1,2-trichloroethane

EC Number:

201-166-9

EC Name:

1,1,2-trichloroethane

Cas Number:

79-00-5

Molecular formula:

C2H3Cl3

IUPAC Name:

1,1,2-trichloroethane

Details on test material:

- Name of test material: 1,1,2-trichloroethane
- Analytical purity: approximately 97%
- Impurities: two peaks of impurity, one of which was possibly tetrachloroethylene, the other was not identified.

Radiolabelled compound:
- Radiochemical purity (if radiolabelling): 96.3%
- Impurities (identity and concentrations): inactive 1,1,2 trichloroethane and 1,1,2,2 tetrachloroethane
- Specific activity (if radiolabelling): 0.38 µCi/mg
- Locations of the label (if radiolabelling): 1,1,2-trichloroethane-1,2-14C. Labelled 1,1,2-trichloroethane prepared by chlorination of ethylene 14C.
- Storage condition of test material: condensed in U-tube and cooled at -80°C.
- Source: The radiochemical centre; Amersham

Radiolabelling:

yes

Test animals

Species:

mouse

Strain:

other: Albino

Sex:

female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

olive oil

Duration and frequency of treatment / exposure:

single i.p. injection

Doses / concentrations

Remarks:

Doses / Concentrations:
0.10, 0.13, 0.14 and 0.19 g/kg (10% in olive oil)

No. of animals per sex per dose / concentration:

1 female at 0.10, 0.13 and 0.19 g/kg
2 females at 0.14 g/kg

Control animals:

no

Results and discussion

Preliminary studies:

1,1,2-trichloroethane was dissolved by addition of alcohol in phosphate buffer (pH 7.2) also containing cysteine. Under these conditions, 1,1,2-trichloroetheane was found to be stable. Determinations of trichloroethane and cysteine in samples of the solutions disclosed no consumption of these compounds during 24 hours

Toxicokinetic / pharmacokinetic studies

Details on absorption:

no data

Details on distribution in tissues:

no data

Details on excretion:

- During the first 24 hours, more than 90% of the activity (82-98 %) was excreted, mainly in the urine (about 76.4% of the administered radioactivity was recovered in urines at 24 hours following administration).
- At 72 hours, about 7 per cent of the activity ( 2-10 %) was recovered in traps 1 and 2 and the oxidation to respiratory carbon dioxide was equivalent to 12 % (8-15 %) of the dose. Less than 1% was found in the faeces, and this activity was probably due to contamination with the urine. Only 2% still remained in the mice after 3 days.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Examination of the urine by paper chromatograpy showed 3 major metabolites and their urinary activity were estimated by isotope dilution analysis:
1- chloracetic acid (6-31%)
2- S-carboxymethylcysteine (free: 29-46%) and (conjugated: 3-10%)
3- thio-diacetic acid (38-42%)
and small amounts 2,2-dichloroethanol, 2,2,2-trichloroethanol, oxalic acid and trichloroacetic acid
The percentage distribution of urinary metabolites of mice receiving chloroacetic 1-14 C acid is shown for comparison (see Table1)

Any other information on results incl. tables

Table 1: Isotope dilution analysis of urinary metabolites from mice receiving 1,1,2 trichloroethane (1,2-14 C). Percentage of urinary activity excreted in 24 hours.

The percentage distribution of urinary metabolites of mice receiving chloroacetic1 -14C acid is shown for comparison.

                                                                 

                                                     

                                             

               

	Mean	Range	Metabolites of chloroacetate
Chloroacetic acid	16(3)	6-31	13
S-carboxymetlycysteine	38 (3)	29-46	39
Conjugated s-carboxymetlycysteine	5 (3)	3-10	3
Thiodiacetic acid	40 (2)	38-42	37
2,2 dichloroethanol	1.4 (3)	0.9-2.1	-
Oxalic acid	0.4 (2)	0.3-0.5	0.2
Trichloroacetic acid	1.9 (3)	1.4-2.3	-
2,2,2 trichloroethanol	0.2 (2)		-

- The figures in brackets are the number of animals

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Under these test conditions, test substance was almost completely excreted 3 day after the i.p. injection. In comparison with the results obtained by the administration of chloroacetic 1-14C-acid in mouse (Yllner, 1970), it is suggested that the metabolism of 1,1,2-trichloroethane proceeds via chloroacetic acid.

Executive summary:

Labelled 1,1,2-trichloroethane (0.38 µci/mg), prepared by chlorination of ethylene -14C, was injected intraperitoneally (0.1 - 0.2 g/kg). The elimination of radioactivity was followed for 3 days. 73 - 87% of the dose was found in the urine, 0.1 - 2% in the faeces (contaminated by urine) and 16 -22% in the expired air. About 3/5 of the expired activity was due to carbon dioxide and the remainder to unchanged trichloroethane. 1 -3% of the dose remained in the animal. Examination of the urine by paper chromatography showed 3 major metabolites and there were estimated by isotope dilution analysis: chloroacetic acid (6 -31%), s-carboxymethylcysteine (29 -46% (free) and 3 -10 (conjugated)) and thio-diacetic acid (38 -42). These results are in good agreement with those obtained by the administration of chloroacetic1-14C-acid. It may therefore be suggested that the metabolism of 1,1,2-trichloroethane proceeds mainly via chloroacetic acid.