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Toxicological information

Basic toxicokinetics

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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 parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
half-life 1st: 41+- 6 minutes
Test no.:
#1
Toxicokinetic parameters:
other: elimination rate constant: 0.017 +- 0.003 minE-1
Test no.:
#1
Toxicokinetic parameters:
other: apparent distribution volume: 0.59 +- 0.07 l/kg
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.