Applied dose

In a study of pregnant rats that were exposed to radiolabeled methyl parathion by single dermal application, half-life elimination rate constants for various tissues ranged from 0.04 to 0.07 hour, highest values noted in plasma, kidneys, and fetus. Of the applied radioactivity, 14% was recovered in the urine in the first hour postapplication. By the end of the 96-hour study, 91% of the applied dose had been recovered in the urine. Fecal excretion accounted for only 3% of the administered dose (Abu-Qare et al. 2000). 

Pyrethroids can also persist in sediments. In one study, alpha-cypermethrin was applied to a pond as an emulsifiable concentrate (Environmental Health Criteria 142). After 16 days of application, 5% of the applied dose was still present in sediment, falling to 3% after a further 17 days. This suggests a half-life of the order of 20-25 days—comparable in magnitude to half-lives measured in temperate soils. 

Three treated cats were sacrificed 0.5, 1, 2, 5, and 10 days after treatment. Radioactivity in urine and feces collected over the 10-day period accounted for 28% and 19% of the applied dose, respectively, but no radioactivity was detected in expired air. Radioactivity in analyzed tissues reached maximal levels at 24 hours (accounting for 8.7% of the applied dose). These data are inadequate for quantitative measurements of the extent of dermal absorption of TOCP, because a significant traction of the applied radioactivity was not accounted for in the analysis, and some of the TOCP may have been ingested by the cats during grooming. 

In Yucatan minipigs dermally exposed for 6 hours to 350 mg/kg, [14C]tributyl phosphate was only poorly absorbed (less than 5% of the applied dose). Absorption in rats treated under similar conditions was much higher (54-58%) (Gatz 1992a, 1992b). 

Patterns of excretion in rats differed among [14C]labeled tricresyl phosphate isomers administered by gavage at dosage levels ranging from 0.5 to 200 mg/kg (NTP 1988). Radioactivity from tn-ortho-cresy phosphate was excreted within 24 hours predominately in urine at all dosage levels ( 70% of applied doses). Radioactivity from trww-cresyl phosphate was excreted predominately in feces at all dosage levels. 

Urinary excretion of radioactivity after a dermal dose of [14C]tributyl phosphate was 29-44% of the applied dose in rats (Gatz 1992b). A large proportion of the dose (24-43%) was recovered in the site wash at the end of the exposure. 

The eye is unique in its therapeutic challenges. An efficient mechanism, that of tears and tear drainage, which quickly eliminates drug solution, makes topical delivery to the eye somewhat different from most other areas of the body [137]. Usually less than 10% of a topically applied dose is absorbed into the eye, leaving the rest of the dose to potentially absorb into the bloodstream [138], resulting in unwanted side effects. The goal of most controlled-delivery systems is to... 

A series of experiments investigated the effect of laser pulse intensity on the distribution of damage. For each pulse intensity, DNA samples were exposed to three different doses. The quantum yield for the formation of lesions, expressed with respect to total DNA bases, was then calculated by linear regression analyses. At all intensities, the formation of lesions was found to be linear with respect to the applied dose. Oxidized nucleosides, including... 

In this study, 4.4 mg of lead equivalent was applied to the skin under a covered wax/plastic patch on the forearms of human subjects of the applied dose, 1.3 mg of lead was not recovered from skin washings. The amount that actually remained in (or on) the skin and the mass balance of the fate of this lead was not determined it may have been absorbed or eliminated from the skin by exfoliation of epidermal cells. Thus, while this study provides evidence for dermal absorption of lead, it did not quantity the fraction of applied dose that was absorbed. The quantitative significance of the dermal absorption pathway as a contributor to lead body burden remains an uncertainty. The wax/plastic patch provided a means by which the lead compounds could permeate or adhere to the skin. The effect of concentration in aqueous solution may cause skin abrasion through enhanced acidity since the lead ion is acidic. Abraded skin is known to promote subsequent higher lead penetration. 

Aniline is lipophilic (pKa of 4.6) and is expected to be rapidly and completely absorbed in the small intestine (Kao et al. 1978). No information on relative bioavailability following inhalation exposure was located, but as indicated by methemoglobin formation during inhalation experiments, systemic absorption by both the inhalation and the percutaneous routes is extensive. Percutaneous absorption of aniline in hairless mice was 4.7% of the nominal applied doses (Susten et al. 1990). 

Fig. 16.1 Plot of percentage of applied dose of pesticide remaining in soil versus depth of soil at various time intervals after application, (a) 31 days, (b) 66 days, (c) 93 days after pesticide application Source Own files...

The most important statistic represents the final plateau of the CDF and the area AUCoo of the corresponding PDF between t = 0 and t = oo. It clearly quantifies the extent of the relevant process, which is in proportion to the applied dose D, or a constant fraction or multiple f D of this, in case of overdose, chemical degradation, etc. Proportionality with dose is violated only if the process contains nonlinear or time-dependent steps such as early loss by defecation, absorption windows, chemical degradation, or non-linear presystemic (first-pass) elimination. 

Plectonema boryanum, were voracious degraders of diflubenzuron (Table III). Just 5 mg of algae cells could metabolize almost 80% of the applied diflubenzuron in just 1 hr. Curiously, this pace was not sustained since 45 mg of algae could degrade only 95% of the applied dose after four days. 

Dorn et al. have studied the fate of epifenonane in polluted water (24). When Glatt River water was fortified with epifenonane at 10 ppm and exposed to open air for four weeks, 61% of the applied dose was recovered as intact epifenonane. Volatility losses amounted to 18% of the applied 3H while metabolites contributed a mere 21%. The characterized metabolites are listed in Table VI. The two major degradation routes involved epoxide modification and benzylic oxidation. 

Soil microorganisms degrade methoprene rapidly and extensively (27). The hydroxy ester was isolated as a minor metabolite over 50% of the applied dose was evolved as 1 C02. Radioactivity from [5-1 0]methoprene incorporated into the humic acid, fulvic acid, and humin fractions of soil. 

The test method is based on the fact that sensitizers induce a proliferation of lymphocytes in the lymph node draining the site of substance administration. The increased proliferation is proportional to the applied dose of the chemical and the potency of the allergen. Hence, the murine LLNA assesses proliferation in a dose-response manner, comparing it to the proliferation in a control group. The ratio of the proliferation after sensitizer application to the control group defines the Stimulation Index (SI). 

The ventilated and perfused human lung lobe was used as described by Linder and co-workers [74], A twofold difference in the appearance of drug and metabolites in the perfusate was found for the two formulations. Small fractions of the applied dose of BDP were immediately detectable in the perfusate and the amount of the major metabolite, beclomethasone-17-propionate (17-BMP), increased over the experimental period. These observations were similar to the clinical observations that BDP is detected rapidly in the plasma after inhalation and that the appearance of the active metabolite 17-BMP occurs rapidly. The kinetic differences between the formulations were explained on the basis of particle size effects with the conclusion that the discriminatory value of this system to examine the lung pharmacokinetics of inhaled medicines in the absence of systemic effects such as hepatic metabolism was apparent. 

Although it is generally considered that response to a toxicant is determined by the availance J Cdt, it must clearly also be expected that there is some threshold of concentration below which the toxicant can be tolerated indefinitely the toxicant arrives so slowly that replacement and repair reactions can compensate for any damage. At the other extreme if the pulse is too rapid the temporary disruption of the vital process may be too short to produce irreversible effects. There is thus likely to be only a defined range of pulse forms producing the specified biological response for any applied dose and since pulse form depends so strongly on P. an optimum value for the partition coefficient within a series of related compounds. 

It was also noted, in the 2002 review of the RfD and RfC processes (US-EPA 2002), that currently, no procedures parallel to the inhalation RfC methodology exist for deriving either oral or dermal human equivalents from animal data. Default factors (usually of 10) are routinely applied to address the issue of animal-to-human extrapolation. Thus, no parallel to the HEC, i.e., a human equivalent dose (HED), is derived nor are other adjustments applied to the animal oral or dermal dose. Instead, assumptions are made regarding the comparability of ingested or applied dose, based... 

Exposure Potential dose Applied dose Internal dose Delivered Biologically... 

After application of radiolabeled PCB, 54% chlorine, to the skin of guinea pigs, 56% of the applied dose was absorbed. ... 

Pharmacokinetics The transdermal absorption of tretinoin from various topical formulations ranged from 1 % to 31 % of applied dose, depending on whether it was applied to healthy skin or dermatitic skin. 

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