Toxicokinetic behavior

The specific toxicokinetic behavior of 1,4-dichlorobenzene in children (and immature laboratory animals) has not been reported. It is not known if appreciable amounts of 1,4-dichlorobenzene penetrate or adversely affect the parental germ cells (or supporting cellular structures) in humans or laboratory... 

Absorption, Distribution, Metabolism, and Excretion. There is an obvious data need to determine the pharmacokinetic and toxicokinetic behavior of HDl in both humans and laboratory animals. Determination of blood levels of inhaled, ingested and dermally absorbed HDl would be difficult, given the very short half-life in biological matrices (Berode et al. 1991) and the rate at which HDl binds to proteins in the blood. Although some information is known about the metabolism of HDl in humans inhaling a known quantity of HDl (Brorson et al. 1990), the rate at which absorption occurs, where the majority of the metabolism of HDl occurs (in the water in the mucous layer of the bronchi as opposed to the blood or the kidney), and the distribution patterns and toxic effects of the metabolite (if any) are not well described. Information in these areas of toxicokinetics and toxicodynamics could also be useful in developing a PBPK/PD model for HDl. Research should focus on the respiratory and dermal routes of exposure. 

Kubota, A., Iwata, H., Tanabe, S., Yoneda, K., Tobata, S., 2004. Levels and toxicokinetic behaviors of PCDD, PCDF, and coplanar PCB congeners in common cormorants from Lake Biwa, Japan. Environ. Sci. Technol. 38, 3853-3859. 

Belfroid, A., Dikkenk, M., Seinen, W., van Gestel, K., Hermens, J. (1994) The toxicokinetic behavior of chlorobenzenes in earthworm (Eisenia andrei) experiments in soil. Environ. Toxicol. Chem. 13, 93-99. 

When measured internal concentrations are lacking, but a time series of effect data is available, then a 1-compartment model may still be useful to describe and analyze the toxicokinetic behavior of a substance. The effects pattern in time provides information on the toxicokinetics as well as toxicodynamics. Jager and Kooijman (2009) demonstrate that the relevant TK parameter can generally be derived from survival data with reasonable accuracy, and discuss how these scaled toxicokinetics relate to the whole body kinetics. 

As is obvious from the huge number of parameters affecting the toxicokinetic behavior, e.g. route of administration. 

Trichloroethane is oxidized to 2,2,2-trichlor-oethanol and trichloroacetic acid by the cytochrome P450 mixed-function oxidase system, which are excreted in the urine while unchanged 1,1,1-trichloroethane, carbon dioxide, and acetylene are excreted in expired air. It is estimated that less than 7% of 1,1,1-trichloroethane is absorbed and metabolized by any exposure route and the toxicokinetic behavior is qualitatively identical across all species. Less than 1% of 1,1,1-trichloroethane remains in the human body after 9 days. 1,1,2-Trichloroethane is metabolized to... 

The pharmacokinetic and toxicokinetic behavior of any isomer cannot be used to predict that of any other ephedrine isomer. The (+) isomer of meth-amphetamine, for example, is a potent CNS stimulant, but the (-)-isomer is merely a decongestant. There is a tendency in the literature to lump together all ephedrine alkaloids and use the term class effect to assume that all the different drugs in that class exert the same effects on the same biological targets. In fact, some of the drugs in the class will be similar in some regards and different in others. 

CYPlA2 may not necessarily reflect toxicokinetic behavior at low exposure levels. This has been illustrated in the model proposed by Brown (1994) in comparing high-exposed humans to low-exposed humans. In addition, serum residues of 2,2 l,4 5,5 hexaCB are lower in prepubertal rats when the total of two doses is high enough to induce P 50 2B (Li et al. 1994). Toxicokinetic data for PCBs do not suggest route-dependent toxicity. 

Derivatization is also useful to detect volatile metabolites. Liu et al. [282] described a specific, rapid, and sensitive in situ derivatization solid-phase microextraction (SPME) method for determination of volatile trichloroethylene (TCE) metabolites, trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol (TCOH), in rat blood. The metabolites were derivatized to their ethyl esters with acidic ethanol, extracted by SPME and then analyzed by gas chromatography/negative chemical ionization mass spectrometry (GC-NCI-MS). After validation, the method was successfully applied to investigate the toxicokinetic behavior of TCE metabolites following an oral dose of TCE. Some of the common derivatization reagents include acetyl chloride and TV-methyl-iV- ft-b u (y Idi methyl si I y I) tro (1 uoroacctam i nc (MTBSTFA) for phenols and aliphatic alcohols and amines, dansyl chloride and diazomethane for phenols, dansyl chloride for amines, acidic ethanol and diazomethane for carboxylic acids, and hydrazine for aldehydes. 

To determine the toxicokinetic behavior of lead (especially lead in bone). 

Toxicokinetic behavior is normally assumed to be similar in animals and humans, at least from a qualitative perspective. On the other hand, certain tumor types in animals may be associated with toxicokinetics or toxicodynamics that are unique to the animal species tested and may not be predictive of carcinogenicity in humans. Very few such examples have been agreed internationally. However, one example is the lack of human relevance of kidney tumors in male rats associated with compounds causing o2u-globulin nephropathy (lARC, Scientific Publication N° 147). Even when a particular tumor type may be discounted, expert judgment must be used in assessing the total tumor profile in any animal experiment. 

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... 

Second, lead s kinetic behavior in vivo provides the means by which one can identify and exploit biomarkers of toxic lead exposures as well as determine the dose portion of critical dose—toxic response relationships for lead poisoning. Measurement of lead in whole blood and its relatively reliable use in determining both systemic lead exposure and the extent of toxic injury (dose—response relationships) is mainly feasible because we understand how Pb s toxicokinetic behavior in blood relates to the temporal and toxicological... 

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