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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:
1 (reliable without restriction)
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Metabolism of ethylene glycol dinitrate and its influence on the blood pressure of the rat
Author:
Clark, D.G. and Litchfield, M.H.
Year:
1967
Bibliographic source:
British Journal of Industrial Medicine, 24:320-325

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A group of rats was subcutaneously injected with EGDN and another with EGMN (ethylene glycol mononitrate); blood pressure and blood concentrations of the parent compounds and inorganic nitrate/nitrite were measured at various time points up to 96 hours after injection.
GLP compliance:
no
Remarks:
Study predates USFDA GLPs

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylene dinitrate
EC Number:
211-063-0
EC Name:
Ethylene dinitrate
Cas Number:
628-96-6
Molecular formula:
C2H4N2O6
IUPAC Name:
ethane-1,2-diyl dinitrate
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: Alderley Park (albino)
Sex:
female

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
96 hours (rats were injected with either EGDN or EGMN and observed for 96 hours)
Doses / concentrations
Remarks:
Doses / Concentrations:
65 mg/kg EGDN; 46 mg/kg EGMN
No. of animals per sex per dose / concentration:
75 rats in the EGDN group; 40 rats in the EGMN group
Control animals:
no
Details on dosing and sampling:
After subcutaneous injection, blood from five rats from each group was taken and analyzed for EGDN, EGMN and inorganic nitrate and nitrite.
Statistics:
Statistical methods were not used. Results were provided as means ± standard deviation. Coefficients of variation were calculated for the points on the curves showing the rise and fall of the compounds in blood at the various time points.

Results and discussion

Main ADME results
Type:
metabolism
Results:
EGDN concentrations peaked at 0.5 hours post-injection, and EGMN concentrations peaked at 3 hours post-injection. Concentrations of EGDN, EGMN and nitrite reached baseline within 12 hours, while nitrate reached baseline after 12 hours.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
EGDN rapidly metabolizes to EGMN (ethylene glycol mononitrate) and then to inorganic nitrate and nitrite

Applicant's summary and conclusion

Conclusions:
Interpretation of results: bioaccumulation potential cannot be judged based on study results
Study design focused on measuring blood levels of EGDN and metabolites following a single subcutaneous injection.

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