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Description of key information

The available studies regarding EGDN pharmacokinetics report that EGDN (ethylene glycol dinitrate) is metabolized into EGMN (ethylene glycol mononitrate) and inorganic nitrate and nitrite. EGDN is rapidly and completely metabolized, and nearly all is excreted as inorganic nitrate.  

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No studies related to absorption or distribution of ethylene glycol dinitrate were located, but several were reviewed related to metabolism and excretion.

A combined in vivo/in vitro study (Clark and Litchfield, 1967) was conducted in which rats were administered EGDN subcutaneously and blood samples were removed at several time points to monitor the degradation of EGDN to EGMN (ethylene glycol mononitrate), inorganic nitrate, and nitrite. The in vitro component involved the incubation of red blood cells with EGDN to monitor its degradation. Degradation of EGDN was nearly complete (99%) at 120 minutes in the in vitro test and reached baseline (i.e., pre-EGDN administration) 8 hours post-injection in the in vivo test. In the in vivo test, EGDN concentrations peaked at 0.5 hours post-injection, and EGMN concentrations peaked at 3 hours post-injection.

A second combined in vivo/in vitro study (Clark and Litchfield, 1969) was conducted in which rats and beagle dogs were administered EGDN subcutaneously and were monitored with respect to EGDN degradation at several time points. The in vitro component involved incubating red blood cells from rats and dogs with EGDN to monitor its degradation. A comparison between species indicated that EGDN metabolism in dogs was more rapid than that of rats. Both species were similar in that pre-treatment of dogs and rats with EGDN for several weeks did not alter in vitro metabolism of a single incubation of EGDN. The patterns of EGDN metabolism reported previously (Clark and Litchfield, 1967) were repeated in the 1969 study.

Excretion was examined in rats that were subcutaneously injected with EGDN or EGMN (Clark and Litchfield 1967). The concentrations of EGDN, EGMN, and inorganic nitrate and nitrite were measured in pooled urine 24 hours after injection. Concentrations were reported in terms of percent of original injection. Following the injection of EGDN, EGDN was 0%, EGMN was 1.5%, Nitrate was 58%, and nitrite was <0.1%, with a total recovery of 59.5%. A similar pattern was observed with the EGMN injection.

References:

Clark, D.G., and M.H. Litchfield. 1967. Metabolism of ethylene glycol dinitrate and its influence on the blood pressure of the rat. British Journal of Industrial Medicine, 24:320-325. 

Clark, D.G., and M.H. Litchfield. 1969. Metabolism of ethylene glycol dinitrate (ethylene dinitrate) in the rat following repeated administration. British Journal of Industrial Medicine, 26:150-155.

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