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Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

73     Toxicokinetics

73.1     Inhalation

No data were found on toxicokinetics of PG via the inhalation route.

73.2     Oral intake

Data indicated that absorption from the gastrointestinal tract is fairly rapid. The maximum plasma concentration of PG in humans was reached within 1 hour after oral exposure (ATSDR 1997).

In dogs, gavage doses of 2, 8 and 12 ml PG/kg water (corresponding to 1036, 4144 and 6216 mg PG/kg b.w.) lead to maximum blood concentrations within 30 minutes for the low dose, and after 2-4 hours for the mid- and high doses (Lehman et al. 1937 – quoted from Mortensen 1993).

In humans, the maximum plasma concentration of PG was reached within 1 hour after oral exposure. No details on the dose were given. (Yu et al. 1985 – quoted from ATSDR, 1997).

The major route of metabolism for PG is by liver alcohol dehydrogenase to lactaldehyde, then to lactic acid and pyruvic acid. An alternative route of metabolism is via phosphorylated glycol. The two metabolites, lactic and pyruvic acids, enter the energy-generating process (i.e. tricarboxylic acid cycle and/or gluconeogenic pathway). Pyruvic acid can also be metabolised further to carbon dioxide and water. (Mortensen 1993, LaKind 1999).

Metabolism of PG in humans was non-linear, based on a saturable clearance. Elimination half-life following oral exposure was about 3.8 hours. The total body clearance in humans was about 100 ml/kg b.w./hour (corresponding to 103.6 g/kg b.w./hour) (Yu et al. 1985 - quoted from ATSDR 1997 and Mortensen 1993).

In another investigation, 20-25% of orally administered PG was eliminated via the urine in 10 hours. (Hanzlik et al. 1939 – quoted from Mortensen 1993).

Dose-dependent elimination was seen in rats, with saturation of the pathways at doses above 5880 mg/kg b.w. and a maximum elimination rate of 0.63 g PG/kg b.w./hour (Morshed et al. 1988 - quoted from ATSDR 1997). 

In cats, PG has been shown to be metabolised to d- and l-lactate. In rats, approximately 33% of an oral dose PG was excreted as the unchanged substance in urine, while dogs excreted 45% unchanged. (Van Winkle 1941, Lehman & Newman 1937 - quoted from Mortensen 1993). 

73.3     Dermal contact

Absorption through damaged skin was studied in 45 patients with second and third degree burns over more than 20% of their total body surface. The sulfadiazine preprations applied dermally over a period of 3-7 contained PG, which was detected in the serum of 24 patients at average levels of 0.08 mg/ml with a range of 0-1.3 mg/ml. PG was detected in the urine of 40 patients at average levels of 1.3 mg/ml, with a range of 0-23.0 mg/ml. (Kulick et al. 1985 – quoted from ATSDR 1997).

73.4     Mode of action

No data were found.

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