2-chloroethanol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD Guideline 417 but data are restricted to plasma concentrations after i.v. application and the corresponding kinetic parameters.

Data source

Reference

Reference Type:

publication

Title:

Disposition kinetics of ethylene oxide, ethylene glycol, and 2-chloroethanol in the dog

Author:

Martis L, Kroes R, Darby TD, Woods EF

Year:

1982

Bibliographic source:

J Toxicol Environm Health 10: 847-856

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

(study restricted to plasma concentrations after i.v. application and the corresponding kinetic parameters)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-chloroethanol

EC Number:

203-459-7

EC Name:

2-chloroethanol

Cas Number:

107-07-3

Molecular formula:

C2H5ClO

IUPAC Name:

2-chloroethan-1-ol

Details on test material:

purity 99%, obtained from Matheson Coleman and Bell, Norwood, Ohio
No further details

Radiolabelling:

no

Test animals

Species:

dog

Strain:

Beagle

Sex:

male

Details on test animals or test system and environmental conditions:

Four male beagle dogs, 2-3 yr old and weighing 16-19 kg, were obtained from Laboratory Research Enterprises, Kalamazoo, Mich. They were housed in standard-size dog cages and were allowed free access to both Ralston Purina Laboratory Canine Diet and tap water. The animals were identified by ear tattoo numbers.
No further data.

Administration / exposure

Route of administration:

intravenous

Vehicle:

water

Details on exposure:

Application volume 1 ml/kg bw; solution injected into the systemic circulation over a 40-s period through a catheter placed in the saphenous vein.

Duration and frequency of treatment / exposure:

single injection

Doses / concentrations

Remarks:

Doses / Concentrations:
46 mg/kg bw

No. of animals per sex per dose / concentration:

4 males

Control animals:

no

Details on study design:

- Dose selection rationale: LD50 values in rats

Details on dosing and sampling:

Blood samples ( 3 ml) for analysis of the test compound and blood gases were collected from the saphenous vein not used for dosing at 0, 0.08, 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 7.0, and 24 h after administration. All blood samples centrifuged and 1-2 ml plasma injected into gas chromatograph.

Statistics:

no data

Results and discussion

Preliminary studies:

no

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The mean plasma concentration immediately after injection was 75 µg/ml; ca. 25 µg/ml were measured after 90 min; and ca. 5 µg/ml 180 min after application.

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 41+- 6 minutes

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

other: elimination rate constant: 0.017 +- 0.003 minE-1

Toxicokinetic parameters 3

Test no.:

#1

Toxicokinetic parameters:

other: apparent distribution volume: 0.59 +- 0.07 l/kg

Toxicokinetic parameters 4

Test no.:

#1

Toxicokinetic parameters:

other: total body clearance: 10.3 +- 1.7 ml/kg x min

Any other information on results incl. tables

Emesis was observed in the dogs the 1st 3 h after administration.

Applicant's summary and conclusion

Conclusions:

In dogs the elimination half-life is 41 minutes after i.v. application of 46 mg/kg bw.

Executive summary:

The study is comparable to OECD Guideline 417 but data are restricted to plasma concentrations after i.v. application and the corresponding kinetic parameters.

Four beagle dogs were i.v. injected with 46 mg/kg bw and blood concentration were measured 0, 0.08, 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 7.0, and 24 h after administration. The plasma concentration immediately after injection was 75 µg/ml; ca. 25 µg/ml were measured after 90 min; and ca. 5 µg/ml 180 min after application.

Conclusion: In dogs the elimination half-life is 41 minutes after i.v. application of 46 mg/kg bw.