Effects intake data

The risk assessment comprises an effect assessment (hazard identification and hazard characterization) and an exposure assessment. The principles for the effect assessment of the active substances are in principle similar to those for existing and new chemicals and are addressed in detail in Chapter 4. Based on the outcome of the effect assessment, an Acceptable Daily Intake (ADI) and an Acceptable Operator Exposure Level (AOEL) are derived, usually from the NOAEL by applying an overall assessment factor addressing differences between experimental effect assessment data (usually from animal studies) and the real human exposure situation, taking into account variability and uncertainty for further details the reader is referred to Chapter 5. As a part of the effect assessment, classification and labeling of the active substance according to the criteria laid down in Directive 67/548/EEC (EEC 1967) is also addressed (Section 2.4.1.8). 

Both variability and uncertainty in threshold and exposure data can be taken into account by using probability distributions to represent the input variables instead of point estimates. The data are plotted in a cumulative distribution curve. For example, threshold data and intake data can be plotted as probability distributions. By combining the threshold distribution and the intake distribution, the output distribution will describe the probability that a part of the population will be exposed at such levels and under such circumstances that adverse effects may occur. Consequently, an approximation of the percentage of the population likely to experience adverse effects at various exposure levels can be made. 

The study presented in Table III demonstrates that aerobic exercise alters energy balance and reduces body fat. The mechanism for this response was addressed by Mayer (65,66). He reported that exercise influenced energy balance by increasing caloric expenditure and by reducing appetite. Other studies have also reported that aerobic exercise produced appetite suppression, particularly in male rats (59,60). These investigators suggested that the effect was related to the intensity and duration of the exercise program. The food intake data for the study described in Table III are presented in Table IV and appear to support this conclusion. After only... 

Effects noted in study and corresponding doses Time-weighted average doses (as mg U/kg/day) calculated by the authors from fluid intake data were males 0.05, 0.20, 0.88,4.82, and 28.70 mg U/kg/day females 0.49, 1.32, and 43.02 mg U/kg/day. Four males showed evidence of Pasteurella multocida infection and were excluded from the study. Two other males in the highest dose groups died prematurely, one from apparent mucoid enteritis and one from apparent acute renal failure. Two others were removed after developing hairball obstructions of the GI tract. No evidence of Pasturella infection... 

The normative lithium requirement of humans is assessed at < 100 tg per day, as all German test subjects of both genders took in between < 100 and > 3500 tg Li per day without showing deficiency symptoms, even at the lowest intake amounts (Anke etal. 1995, 1997b). However, deficiency symptoms may occur in dialysis patients, in kidney failure and in parenteral nutrition. Based on intake data in different countries, Schrauzer (2002) suggested a provisional recommended dietary allowance (RDA) of 1 mg Li per day for a 70-kg adult. Compared with the above intake data, therapeutic effectiveness in the treatment of manic-depressive disorders is achieved at doses of 140 to 280 mg Li per day - about 100 to 300 times higher than RDA (Schou... 

What has been reported previously leads to the question of who should receive calcium and vitamin D supplementation without causing harmful effects. Current data do not allow definite conclusions to be drawn, but require further independent confirmation, since in numerous large studies, combined calcium and vitamin D supplementation did not increase cardiovascular events, even in the most frail and elderly populations [lO ]. Nevertheless, it seems appropriate to correct calcium deficiency preferably by enhancing dietary intake and to target supplementation on individuals at high risk of fracture or in whom calcium and vitamin D deficiency is highly prevalent. 

After intakes have been estimated, they arc organized by population, as appropriate. Then, tlie sources of uncertainty (e.g., variability in analytical data, modeling results, parameter assumptions) and their effect on tlie exposure estimates are evaluated and sunuiumzed. Tliis information on uncertainty is important to site decision-makers who must evaluate tlie results of the e.xposure... 

Data concerning gastric cancer are scarce. The prospective Netherlands Cohort Study found no correlation between lutein dietary intake and gastric cancer risk, whereas findings from the Physicians Health Study and the ATBC study reported no effect of P-carotene on gastric cancer incidence. Two case-control studies and three intervention trials (ATBC, CARET, and the Physicians Health Study ) showed no association of P-carotene, lycopene, lutein, zeaxanthin, and P-cryptoxanthin. 

Epidemiological data on carotenoids and cerebral infarcts or strokes indicate a protective effect of P-carotene and lycopene. Indeed, the Basel prospective study, the Kuopio Ischaemic Heart Disease Risk Factor study, and the Physicians Health Study " have shown an inverse correlation between carotenoid plasma level and risk of stroke. In the same way, Hirvonen et al. demonstrated, in findings from the ATBC cancer prevention stndy, an inverse association between P-carotene dietary intake and stroke. However, clinical data on carotenoids and stroke are nonexistent and they are needed to confirm this possible protective effect of carotenoids on stroke. 

Curcumin (diferuloyl methane) is the main pigment of turmeric. It is widely used as a colorant and preservative agent. No data regarding its daily intake in western countries are available intake may reach 80 to 200 mg in adult Indians. To date, no study has explored the effect of curcumin consumption on the incidence of diseases, but many beneficial effects on health have been reported in cell and animal models. These include anti-carcinogenic, anti-diabetic, anti-atherosclerotic, and anti-Alzheimer s disease properties. ... 

NOAEL (no-observed-adverse-effect level) is defined as the highest dose at which no adverse effects are observed in the most susceptible animal species. The NOAEL is used as a basis for setting human safety standards for acceptable daily intakes (ADIs), taking into account uncertainty factors for extrapolation from animals to humans and inter-individual variabilities of humans. The adequacy of any margin of safety or margin of exposure must consider the nature and quality of the available hazard identification and dose-response data and the reliability and relevance of the exposure estimations. In some cases, no adverse endpoint can be identified such as for many naturally occurring compounds that are widespread in foods. In that case, an ADI Not Specified is assigned. ... 

Generation of data on the nutrient content of agricultural products and foods forms the basis for estimating nutrient intakes of populations via dietary surveys, nutritional labelling for consumer protection, nutrition education for consumer food choice, home and institution menu planning and food purchase, and for research in nutrient requirements and metabolism, toxicant chemical composition is used to assess effects of farm management practices, crop culture, and food processing on chemical content and implications for human health. 

Significant scientific attention has focused on caffeine and its health effects. However, limited data are available for the actual dietary consumption of caffeine or theobromine from individual foods. Even less data exist on the contribution of cocoa and chocolate foods to methylxanthine intake. 

Foods derived from cocoa beans have been consumed by humans since at least 460 to 480 AD, presumably with no major health effects. Most chocolate is consumed in the form of chocolate confectionery. On the basis of USDA dietary survey data, 12% of the population consumed chocolate confectionery at least once in three days with an average intake of 50.5 g... 

Significant scientific attention has focused on caffeine and its health effects. However, limited data is available for the actual dietary consumption of caffeine or theobromine from individual foods. Even less data exists on the contribution of cocoa and chocolate foods to methylxanthine intake. In children and teenagers, the major dietary source of caffeine was found to be tea, followed by soft drinks and coffee, respectively. Although chocolate foods and beverages ranked the lowest of these dietary sources to provide caffeine, they do constitute the major source of dietary theobromine. In order to gain a better insight into the amount of methylxanthines consumed via the diet, more studies on the methylxanthine content of chocolate foods, as well as beverages, are needed. 

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