Dietary Route Research Articles

Teratogenic effects of benomyl in the Wistar rat and CD-1 mouse, with emphasis on the route of administration

Benomyl, a systemic fungicide whose molecular basis of action is inhibition of tubulin polymerization, was administered during organogenesis via the dietary and gavage routes to pregnant Wistar rats, and via the gavage route to pregnant CD-1 mice. Benomyl was fetotoxic and teratogenic in both species via the po route of administration, producing a broad spectrum of malformations at a dose of 62.5 mg/kg/day in the rat and 100 mg/kg/day in the mouse. Via the dietary route of administration, benomyl produced fetotoxicity, but no teratogenic effects. The fetotoxic potential of benomyl from dietary exposure was approximately an order of magnitude less effective than from gavage exposure. Benomyl did not affect postnatal growth, viability, or locomotor activity at subteratogenic doses. The most sensitive indicator of perinatal exposure to benomyl via the po route of administration was a permanent reduction in testes and accessory sex gland weight noted in male offspring of dams receiving 31.2 mg/kg/day benomyl during gestation and lactation. No effects on any parameters were evident in rats receiving 15.6 mg/kg/day by po gavage. The relevance of the two routes of administration for risk extrapolation is discussed.

Petroleum compounds in the marine food web: short-term experiments on the fate of naphthalene in Calanus

Adult female Calanus helgolandicus Claus immersed for 24 h in sea-water solutions of [1-14C]naphthalene accumulated a detectable quantity (3.6 pg/animal) from concentrations as low as 0.10 μg/1.Feeding experiments using barnacle nauplii or diatoms as foods showed that the dietary route of entry was more important quantitatively than direct uptake from solution in that in order to ensure that the same quantity of radioactivity in the animals was attained by the two routes the level of hydrocarbon in solution had always to be far greater than that present as paniculate food. Relevant to these observations was the further finding that after naphthalene had been accumulated directly from solution in sea water depuration was rapid and only a small fraction, less than 5%, of the original radioactivity could be detected after 10 days: by contrast, when the hydrocarbon was taken up by way of the food depuration was much slower, so that at the end of 10 days about a third of the original level of radioactivity still remained in the animals. Short-term experiments in which Calanus were fed on labelled diets for 24 h under bacteria-free conditions showed that at the end of this period over 90% of the radioactivity in the animals was present as unchanged naphthalene. However, more than two thirds of that released by the animals was in some form other than the hydrocarbon, a finding consistent with the view that Calanus is able to metabolize it.

Whole-body Retention, Tissue Distribution and Excretion of Selenium-75 after Oral and Intravenous Administration in Lambs Fed Varying Selenium Intakes

Selenium metabolism was studied by measuring whole-body retention, urine and fecal losses and retention in selected tissues following administration of 75Se to lambs fed varying levels of dietary selenium. Whole-body loss of 75Se 48 to 336 hours after administration of the isotope could be described by a first-order rate constant which was inversely proportional to the dietary level of selenium. Intravenous injection of 75Se resulted in a higher retention than oral administration, especially on low dietary intakes of selenium. The concentration of 75Se in various tissues was inversely related to the dietary selenium level. Kidney and liver tissue were consistently higher in 75Se concentration than any other internal organ tissue. Of the total 75Se dose administered, the carcass retained the highest amount, being indirectly proportional to the dietary selenium level. The major pathways of 75Se excretion are the feces and urine. The kidney exhibited an unlimited ability to excrete 75Se. Since a significant amount of 75Se excretion was not accounted for as urine and fecal loss, respiratory loss of volatile selenium products formed in the rumen is offered as a possible explanation. Relative importance of these three excretory pathways depended upon dietary selenium intake level and route of 75Se administration.