Toxicokinetic properties

Practically all toxicokinetic properties reported are based on the results from acute exposure studies. Generally, no information was available regarding intermediate or chronic exposure to methyl parathion. Because methyl parathion is an enzyme inhibitor, the kinetics of metabolism during chronic exposure could differ from those seen during acute exposure. Similarly, excretion kinetics may differ with time. Thus, additional studies on the distribution, metabolism, and excretion of methyl parathion and its toxic metabolite, methyl paraoxon, during intermediate and chronic exposure are needed to assess the potential for toxicity following longer-duration exposures. 

No studies were located that examined the toxicokinetics of mineral oil, organophosphate ester, or polyalphaolefin hydraulic fluids in humans or animals, with the exception of a study examining absorption in rats after exposure to a hydraulic fluid containing 99.9% cyclotriphosphazene (Kinkead and Bashe 1987) and the absorption and metabolism of Reolube HYD46, another organophosphate hydraulic fluid (Ciba-Geigy 1985). This section, therefore, discusses available information on the toxicokinetics of major components of these classes of hydraulic fluids or of materials that maybe expected to display similar toxicokinetic properties based on similar physical and chemical characteristics. It should be emphasized that many hydraulic fluids are complex mixtures of chemicals that may include some chemicals which may not share toxicokinetic properties with the major components. 

Comparative Toxicokinetics. The toxicokinetics database is wholly inadequate with respect to comparing toxicokinetics across species, largely because of the dearth of baseline data regarding absorption, distribution, metabolism, and excretion in any species after exposure to mineral oil hydraulic fluids, organophosphate ester hydraulic fluids, or polyalphaolefin hydraulic fluids. Also, no studies were located on the toxicokinetic properties of hydraulic fluids in humans. 

The effect of any chemical at a biological target depends on its ability to attain a target site concentration that exceeds the threshold required to ehcit the response. The intensity and duration of the response depends on the toxicokinetic properties of the compound (absorption, distribution, metabolism, and excretion) and the nature of the target site interaction (reversible, irreversible). If recovery is complete between successive exposures, no cumulative toxicity is to be expected. However, a short-term acute exposure could potentially add to the long-term burden of a persistent chemical and be relevant for the magnitude of the chronic effect. 

For acute and short-term exposures difference in the toxicokinetic properties, which wUl result in different times to maximum effect for the individual compounds, are critical in determining... 

The Nickel Producers Environmental Research Association (NiPERA) is sponsoring research to develop toxicokinetic models to be used to predict health effects in humans and is comparing the toxicokinetic properties of nickel in various animal species. 

Comparative Toxicokinetics. The animal data indicate that the nervous system is a sensitive target of toxicity for aluminum following oral exposure, as summarized in the Data Needs sections on Neurotoxicity. Although the interpretation of the human data is limited by poor exposure characterization, the occupational exposure studies suggest that neurotoxicity is also a sensitive end point following inhalation exposure (Hanninen et al. 1974 Hosovski et al. 1990 Rifat et al. 1990 Sim et al. 1997 Sjogren et al. 1996 White et al. 1992). The toxicokinetic properties of aluminum have been extensively studied in human and animals. The results of these studies suggest that the absorption, distribution, and excretion properties of aluminum are similar across species. 

There is a limited amount of data on the toxicokinetic properties of CDDs in children or immature animals. A toxicokinetic model was constructed that accurately predicted the lifetime concentrations of 2,3,7,8-TCDD in adipose tissue, blood, liver, and feces at different ages (Kreuzer et al. 1997). In formula-fed infants, the model predicted that 2,3,7,8-TCDD lipid levels would decrease during the first... 

The combination of the health-relevant time-window and the toxicokinetic properties of the agent of interest determine the optimal exposure assessment strategy. Dioxin, a contaminant of chlorophenoxy herbicides and fungicides, has a relatively long biological half-life, estimated at about seven years and is measurable in serum. Serum measurements of dioxin are therefore relatively stable, and simple first-order kinetics have been used to back-estimate serum dioxin levels on the basis of an occupational history. Such exposure data have been used quite successfully in epidemiological analyses of cohorts of pesticide producers (Hooiveld et al, 1998). 

Discussion of the empirical clearance rate and other toxicokinetic properties of the chemical. For example, does the concentration causing the effect vary significantly with duration or number of exposures ... 

The structural similarity of abrin to ricin is reflected also in its toxicokinetic properties with... 

The toxicokinetic properties of Stoddard solvent are not well defined by the available data. Some toxicokinetic data that are specific to the three classes of Stoddard solvent components (i.e., alkanes, cycloalkanes, and aromatics) are available. 

Therefore, additional studies designed to assess the toxicokinetic properties of zinc following inhalation and dermal exposures would be useful. 

Only few studies have been conducted to analyze the toxicokinetic properties of types I and II in laboratory animals [27-29]. The lipophilicity of pyrethroids also enables rapid access to tissues, including the CNS. Non-cyano pyrethroids (permethrin) as well as cyano pyrethroids (deltamethrin and cyhalothrin) have an accumulation in the nervous tissues [25, 28, 29]. The toxicokinetic behavior of these pyrethroids revealed prolonged elimination half-lives (typically in the order of 10 h but may be larger) and high concentrations in several regions of the brain... 

---