The effect of a high-fat meal on the pharmacodynamics of a model lipophilic compound that binds extensively to triglyceride-rich lipoproteins.

A high-fat meal induces transient hyperlipidemia characterized by elevated triglyceride-rich lipoproteins (TRL) which are composed mainly of chylomicrons. The purpose of this work was to investigate the effect of this transient hyperlipidemia on the pharmacodynamics of lipophilic drugs, using DDT as a model compound since it binds extensively to TRL and has a distinct neurotoxic effect. The postprandial hyperlipidemia in rats was induced by oral administration of peanut oil and was monitored by measurement of plasma triglyceride levels. The control group received water instead of oil. The rats received a continuous intravenous infusion of DDT (10 mg/h) until onset of a predefined pharmacodynamic endpoint (facial muscle tremor). Plasma and brain samples were then obtained and assayed for DDT. Rats with postprandial hyperlipidemia required higher dose of DDT to induce onset of facial muscle tremor. At the pharmacodynamic endpoint, oil treated rats had significantly higher concentrations of DDT in plasma and in the chylomicron fraction, but DDT brain concentrations were the same in both groups. In conclusion, a high-fat meal induces postprandial hyperlipidemia that may significantly alter the pharmacological profile of lipophilic compounds that bind to TRL. This is due to alteration of the distribution characteristics of the lipophilic compound through its association with postprandial lipoproteins. However, this pharmacokinetic phenomenon did not affect the concentration-effect relationship at the site of action in the brain.

Leaf-air transfer of organochlorine pesticides from three selected vegetables.

The leaf-air transfer of organochlorine pesticides (OCPs) in three kinds of vegetables, namely lettuce, romaine and garlic leaves was investigated. It was found that although the uptake of OCPs by the three selected vegetables was similar under controlled conditions, the depuration varied significantly among chemicals and plant species in terms of elimination rate, final residue of each OCPs, as well as the effect of temperature on the residue of OCPs in the vegetables. The results indicated that neither QCB nor HCB could be trapped tightly by any of the three selected vegetables, in contrast, p,p'-DDT could be retained effectively by all of them; the retainment of alpha-HCH, gamma-HCH, p,p'-DDE, was dependent on the vegetable species, of which the garlic leaf had the biggest ability to trap them. Our work provided insight into the behavior of OCPs in the agroecosystem.

Comparative assessment of endocrine modulators with oestrogenic activity. II. Persistent organochlorine pollutants.

Risk assessments of synthetic chemicals with oestrogen-like activity must take into account the high dietary levels of natural endocrine modulators in food. In view of current regulations of the European Union, a hygiene-based margin of safety (HBMOS) for xeno-oestrogens was defined as a quotient of estimated human daily intakes weighted by relative rodent in vivo potencies of the compounds. Such comparisons of intakes and potencies of natural isoflavones, with short half-lives, with those of polychlorinated organic pollutants (POP) displaying significant toxicokinetic accumulation, deserves the special consideration of toxicokinetics. For slowly accumulating compounds such comparison is much more favourable when based on comparative blood and tissue levels, not on scenarios of daily exposures. Observing these principles, the present communication extends the HBMOS concept to POP, using o,p'-DDT, the oestrogenic component of DDT mixtures, as a prototype. An HBMOS of 137 is derived for o,p'-DDT indicative of a sufficient margin of safety to ensure the absence of risk to human health due to its hormonal action, under exposure conditions now prevailing in Western countries.

A comparison between intubation and food addition as routes of oral exposure for northern bobwhites to DDT insecticide.

Our objective was to compare two methods of oral dosing of p,p'-DDT (1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane) on uptake of DDT metabolites and isomers (i.e., p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE, p,p'-DDD, o,p'-DDD) in livers and brains. p,p'-DDT was administered to northern bobwhite (Colinus virginianus) by intubation with corn oil or as a feed additive for 56 days. When adjusted for amount of DDT consumed, total DDT (sigma DDT, the summation of all DDT metabolites and isomers) and p,p'-DDE concentrations differed significantly (P less than 0.10) in both brains and livers, whereas p,p'-DDD differed only in brains and p,p'-DDT differed only in livers. Paired comparisons between brains and livers differed significantly for sigma DDT, (P less than 0.05), p,p'-DDE (P less than 0.05) and p,p'-DDT (P less than 0.1) for both intubated and food-dosed treatment groups, whereas p,p'-DDD (P less than 0.05) differed only in the intubated group. We concluded that method of oral exposure affected the uptake of DDT in livers and brains for northern bobwhites.