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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
A study of mortality and urinary excretion of oxalate in male rats following acute experimental intoxication with diethylene glycol.
Author:
Durand A, Auzepy P, Hebert JL, Trieu TC
Year:
1976
Bibliographic source:
Europ J Intens Carc Med 2: 143-146

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
Mortality and urinary excretion of oxalate.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Duration and frequency of treatment / exposure:
The daily average urinary excretion of oxalate was measured on 70 control rats after 24 hours of fasting.
Doses / concentrations
Dose / conc.:
15 other: mL/kg bw
Remarks:
Each trial group was given a single LD50 dose of the test substance (15 mL/kg bw)
No. of animals per sex per dose:
- Groups 1, 2, 3, 4, 5: 30 rats
- Groups 6 and 7: 15 rats
Details on dosing and sampling:
The urinary concentration of oxalate was determined by the colorimetric method of Hodgkinson and Williams. The analysis of the calcium oxalate crystals was made on the sediment of the daily urine output with a polarizing microscope and the birefractive crystals were counted by fields (ohne approx. for the high score).
First, the daily average urinary excretion of oxalate was measured on 70 control rats after 24 hours of fasting. Then, each trial group was given a single LD50 dose of the test substance (15 ml/kg of body weight as according to Fitzhugh and Nelson) by a gastroesophageal tube. Urinary excretion of oxalate was then determined for two days and mortality was noted each day until the animals were sacrificed for histological studies 5 days after the intoxication. Seven groups were tested; for details, see table below.
Statistics:
The statistical analysis was performed using the Student's t test for small samples.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Acute intoxication by diethylene glycol (LD 50) in male rats is associated with a considerable urinary excretion of oxalate, which is significantly decreased by alkalinisation and/or intraperitoneal injection of ethanol with hydration.

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Conclusions:
Acute intoxication by diethylene glycol (LD 50) in male rats is associated with a considerable urinary excretion of oxalate, which is significantly decreased by alkalinisation and/or intraperitoneal injection of ethanol with hydration. Mortality during the five days following intoxication is significantly decreased by major hydration only or together with pyridoxine administration, but is cancelled by major hydration together with alkalinisation or intraperitoneal administration of ethanol, plus hydration, with or without alkalinisation. It might be inferred that diethylene glycol has the same metabolic pathway as ethylene glycol and treatment of acute intoxication by diethylene glycol should be the same as that of acute poisoning with ethylene glycol.