Intake dose

EUSES. As in the case of USEtox model, the present model provides outputs such as human intake fraction of a certain substance for different exposure pathways. In the present case study, estimation of the human intake doses for Guiyu was calculated. These results were compared with the incidence and severity of the effects (dose-response assessment). 

On the other hand, values of intake doses obtained with USEtox for human beings are presented in Table 5. 

After an intensive research on maximum intake dose permitted for human beings through different pathways, it has been observed that the most reliable was to consider the total intake since the particular intake pathway data were not clear enough. After comparing these values, the following statements can be made ... 

In this case, a similar situation to the previous one of the environmental compartments occurs. The fact that the intake dose is calculated for the whole China population supposes that these intake doses are lower than the expected again. They are calculated taking into account the emissions coming mainly from the polluted spots but considering all the Chinese population as a potential receptor. However, not all the citizens are affected by these intake doses. In addition, as mentioned before the potential underestimation of the treated e-waste volume in China could be the cause of these low values. 

These PECs fit well with data from Guiyu town obtained from a literature review (see Annex 1). It can be observed that the most impacted compartments are soil and sediments. The value of total regional intake doses of DeBDE for human beings is... 

Table 5 Intake doses for human beings provided by the USEtox model... 

Intake dose through (mg (kg day)-1) Air Drinking water Exposed produce Unexposed produce Meat Dairy products Fish Total ... 

It is interesting to mention that USEtox is mainly a tool for LCIA studies where characterization factors are obtained for a wide list of substances. However, the model also provides intermediate output parameters (e.g., intake doses, concentrations in environmental compartments, substance exposure) that can be used for risk assessment studies. This was the case in the present study comparing the values from USEtox with reference limit values. 

The relationship between nicotine intake and steady state cotinine blood levels can be expressed in the following way, based on steady state exposnre conditions Dnic = CLcot X CcoT f, where Dnic is the intake (dose) of nicotine, CLcot is the clearance of cotinine, Ccot is the steady state blood concentration of cotinine and f is the fraction of nicotine converted to cotinine. On rearranging the equation, Dnic = (CLcot f) x Ccot = K x Ccot where K is a constant that converts a given blood level of cotinine to nicotine intake. On average, K = 0.08 mg 24h ng ml (range 0.05-1.1, CV = 21.9%). Thus, a cotinine level of 30 ng ml in blood corresponds on average to a nicotine intake of 24 mg per day. 

The US-EPA Consolidated Human Activity Database (CHAD) (US-EPA 2007b) contains data obtained from preexisting human activity studies that were collected at city, state, and national levels. CHAD is intended to be an input file for exposure/intake dose modeling and/or statistical analysis. CHAD is a master database providing access to other human activity databases using a consistent format. This facilitates access and retrieval of activity/and questionnaire information from those databases that US-EPA currently has access to and uses in its various regulatory analyses undertaken by program offices. 

In 2007, Boocock et al. [2007] were the first to publish a complete phase I dose pharmacokinetic study in humans. Ten healthy volunteers were recruited to consume single doses of oral resveratrol (0.5, 1, 2.5, or 5 g). Consumption of resveratrol did not cause serious adverse events. Analyses of resveratrol and its metabolites were performed by LC-MS/MS. In plasma in all intake doses resveratrol-3-sulfate (56%) was the highest metabolite, the second and third metabolites were monoglucuronides (17 and 23%, respectively), and, finally, the lowest was free resveratrol (5%). Resveratrol was rapidly absorbed, the 7/nax for all metabolites ranged between 0.8 and 2.4 h, although the half-lives of free resveratrol and the conjugated forms remained for a long time in plasma, between 2.9 and 11.5 h. 

The widespread detection of phthalate metabolites in human urine has produced questions about public-health risks, especially with regard to antiandrogen effects that can influence male gonadal development (Gray et al. 2000 Parks et al. 2000). The extrapolation from urinary biomonitoring results to exposure and risk assessment has been facilitated by calculations that convert urinary metabolite concentrations to intake dose of the parent phthalate (Koo et al. 2002 Koch et al. 2003 Kohn et al. 2000 David 2000). The parent diester phthalates are rapidly and completely metabolized to the monoester metabolites, which are rapidly cleared by the kidney. Those features allow one to assume that the daily excretion rate of metabolite is equal to the daily intake rate of the parent chemical. Furthermore,... 

For persistent lipid-soluble compounds, conversion of blood or adipose tissue biomonitoring results to body burden and intake dose is feasible even with simple one-compartment models, although multicompartment physiologic models can provide a more flexible and improved tool for estimating dose. 

Case Example of Use of One-Compartment Pharmacokinetic Model to Estimate Intake Dose of Slowly Cleared Lipid-Soluble Chemicals 2,3,7,8-TCDD... 

Chapter 5 describes a simple one-compartment modeling approach that can yield screening-level estimates of intake dose based on biomonitoring results (chemical concentration in blood or lipid) for slowly cleared lipid-soluble chemicals. The overall approach is shown below (Figure B-l is reproduced from Chapter 5) ... 

Further interpretation of urinary biomonitoring data has been attempted with pharmacokinetic simulations by using a relatively simple one-compartment model to convert urinary concentrations to intake doses (Rigas et al. 2001 Shurdut et al. 1998 Barr 2005). The key assumption needed for back-calculation of intake dose from urinary concentration is that 70% of the dose is excreted in the urine as TCP over a relatively short period. 

Hazard quotient Ratio of the estimated chemical intake (dose) to a reference dose level below which adverse health effects are unlikely. The value is used to evaluate the potential for noncancer health effects, such as organ damage, from chemical exposures (from http //web.ead.anl.gov/uranium/glossacro last accessed July 2010). 

When calculating the inhalation intake, dose coefficients and respiration intensity data (8100 m /year) for adults given in RSS-99 [6] were used. For lack of detailed data on relative concentrations of components in the inhaled air for specific NS and RC storage and basing meas, the appropriate recommendations of IAEA [7] were applied. 

Non-carcinogenic risk is normally characterized in terms of a hazard index defined by the ratio of the estimated intake dose from exposure to the reference dose (RfD). Reference doses depend on the exposure route and may be used with its exposure data. The hazard index is calculated as... 

The carcinogenic risk may be defined as the chronic daily intake dose (as developed in the exposure assessment) multiplied by the carcinogenic slope factor (as selected by the toxicity assessment). The product is the probability of developing cancer during lifetime from exposure to this chemical. 

The described symptoms may not always have relevance for human exposure. Nevertheless, the EU s Scientific Committee for Food (SCF) has recently published its risk assessment for dioxins and the PCBs related to the dioxins, and state that a weekly intake dose of 7 pg of dioxin/kg of body weight (or lower) is tolerable. The Environmental Protection Agency s Science Advisory Board in the U.S. also concluded that dioxins might give health effects at levels close to background exposures (see Kaiser, 2000). One of the problems is to decide if its toxicity has a threshold, and as yet, it has not been possible to agree on a safe dose. 

OCPs can cause a range of adverse human health effects, such as cancer, reproductive effects, and acute and chronic injury to the nervous system. Many previous investigations show that the increasing consumption of contaminated seafood has resulted in an elevated pollutants residual in human tissues compared with that in older generations (Asplund et al., 1994). The World Health Organization (WHO) and Food and Agriculture Organization (FAO) have proposed an acceptable daily intake (ADI) for DDTs at 5,000 ng/(kg d) (Zhulidov et al., 2002). For a 70-kg human, if he/she consumes 1 kg aquatic product a day from the Bohai Sea with a mean DDTs level of 199 or 52 ng/g, his/her daily intake dose is 2,850 ng/kg. This value is well below the proposed ADI. However, the ADIs of DDT are 400 and 600 ng/(kg d) in... 

Due to uncertainties and inconsistencies in the epidemiological studies, no health-based HBM values for perfluorinated compounds in blood could be set from the available data yet. A further approach to interpret perfluorinated compounds levels in HBM is to derive HBM values from corresponding tolerable intake doses, such like the tolerable daily intake (TDI). This concept has been proposed by the German Human Biomonitoring Commission (2007). The Commission is aware of the uncertainties of such derivation and estimates. 

Health-based HBM values can be derived on the basis of epidemiological studies, toxicological basis with toxicokinetic extrapolation which provides a concentration of a substance or its metabolites corresponding to tolerable intake doses. However, HBM values for PFC have not been derived yet. 

Human Biomonitoring Commission (2007) Umweltbundesamt, Derivatirai of human biomonitoring (HBM) values based on tolerable intake doses. Bundesgesundheitsbl Gesnndheits-forsch Gesundheitsschutz 50 251-254, in German... 

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