Languages:
The source document for this Digest states:
EXPOSURE
Background exposure
Human exposure to PCDDs, PCDFs, and PCBs may occur through background (environmental) exposure, and accidental and occupational contamination. Over 90 percent of human background exposure is estimated to occur through the diet, with food from animal origin being the predominant source. PCDDs and PCDFs contamination of food is primarily caused by deposition of emissions from various sources (e.g. waste incineration, production of chemicals) on farmland and waterbodies followed by bioaccumulation up terrestrial and aquatic foodchains. Other sources may include contaminated feed for cattle, chicken and farmed fish, improper application of sewage sludge, flooding of pastures, waste effluents and certain types of food processing.
Source & ©: WHO-IPCS 
re-evaluation of the Tolerable Daily Intake (TDI) page 3
The source document for this Digest states:
The available information derived from numerous studies in industrialized countries indicates a daily intake of PCDDs and PCDFs in the order of 50-200 pg I-TEQ/person/day, or 1-3 pg I-TEQ/kg bw/day for a 60 kg adult. This results in average human background levels in the range of 10-30 pg I-TEQ/g lipid, equivalent to a body burden of 2-6 ng I-TEQ/kg body weight. If the dioxin-like PCBs (non-ortho and mono-ortho PCBs) are also considered, the daily TEQ intake can be a factor of 2-3 higher. Special consumption habits, particularly one low in animal fat or consumption of highly contaminated food stuffs may lead to lower or higher TEQ intake values, respectively. The intake of PCDDs/PCDFs and PCBs increases during childhood and stabilizes in adults of about 20 years of age.
Source & ©: WHO-IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 3
The source document for this Digest states:
However, the intake on a per kilogram basis decreases in this period due to the increasing body weight. Despite differences in the absolute levels of PCDDs/PCDFs/PCBs, the congener profiles caused by background contamination are usually very similar. Recent studies from countries which started to implement measures to reduce dioxin emissions in the late 80s, such as The Netherlands, United Kingdom and Germany, clearly show decreasing PCDD/PCDF and PCB levels in food and consequently a significantly lower dietary intake of these compounds by almost a factor of 2 within the past 7 years.
Source & ©: WHO-IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 3
The source document for this Digest states:
Compared to adults, the daily intake of PCDDs/PCDFs and PCBs for breast fed babies is still 1-2 orders of magnitude higher on a per body weight basis. The latest WHO field study showed differences between the PCDD/PCDF and PCB contamination of breast milk, with higher mean levels in industrialized areas (10-35 pg I-TEQ/g milk fat) and lower mean levels in developing countries (< 10 pg I-TEQ/g milk fat). Within one country an individual variation of a factor of 5-10 was observed for most congeners, mainly due to age of the mother, number of breastfed babies, length of nursing period and consumption habits. There is now clear evidence of a decrease in PCDD/PCDF levels in human milk over time in almost every region for which suitable data exist. The WHO field study also showed that the highest rates of decrease have been in the areas with the highest initial concentrations. Latest results from Germany revealed a decrease of PCDD/PCDF levels in human milk of approximately 65% between 1989 and 1997. These data support the substantial reduction in intake of PCDDs and PCDFs in the past few years.
Source & ©: WHO-IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 3
The source document for this Digest states:
Well-known examples of accidental exposure of the local population to PCDDs, PCDFs and PCBs include the incident at Seveso, and fires in PCB filled electrical equipment. In Seveso, the serum levels for 2,3,7,8-TCDD ranged up to 56000 pg/g lipid, with median levels of 450 pg/g lipid for Zone A and 126 pg/g lipid for Zone B. High exposure may also be caused by food items accidentally contaminated. Known examples are the contamination of edible oil, such as the Yusho (Japan) and Yu-Cheng (Taiwan) food poisoning. For a group of Yusho patients, average intake by ingestion of the Kanemi rice oil contaminated with PCBs, PCDFs and polychlorinated quarterphenyls (PCQs) was estimated at 154000 pg I-TEQ/kg bw/day, which is five orders of magnitude higher than the reported average background intake in several countries.
Source & ©: WHO-IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 3-4
The source document for this Digest states:
Industrial activities in which 2,3,7,8-TCDD and related compounds are unintentionally produced, such as waste incineration or production of certain pesticides or chemicals may also result in additional human exposure. While many industrial sources of 2,3,7,8-TCDD and related compounds have been identified and worker exposure has been reduced or eliminated historic median 2,3,7,8-TCDD levels in blood of highly exposed workers, estimated by extrapolation back to the time of last exposures, ranged from 140 to 2000 pg/g lipid. These estimates are 1-3 orders of magnitude higher than the blood levels measured in the general population. Body burdens caused by accidental or occupational exposure show congener patterns that are different from background exposure and are normally dominated by only a few congeners. This is because of direct exposure vs. indirect exposure through the food supply where bioaccumulation may modify congener patterns.
Source & ©: WHO - IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 4
The source document for this Digest states:
A broad variety of data primarily on TCDD but also on other members of the class of dioxin-like compounds has shown the importance of the Ah (dioxin) receptor in mediating the biological effects of dioxin. These data have been collected in many experimental models in multiple species including humans. The precise chain of molecular events by which the ligand-activated receptor elicits these effects is not yet fully understood. However, alterations in key biochemical and cellular functions are expected to form the basis for dioxin toxicity. Pharmacological structure-activity and mouse genetic studies using Ah-receptor-deficient animals and cells have demonstrated a key role for the receptor in mediating toxic effects of TCDD. For instance, a reduction or lack of acute toxicity in receptor-deficient mice has been documented. The activated receptor exerts two major types of functions: enhancement of transcription of a battery of genes containing responsive elements in their promoter regions, and immediate activation of tyrosine kinases. A number of genes encoding drug-metabolizing enzymes, such as cytochrome P4501A1, 1A2, 1B1, glutathione S-transferase, and UDP-glucuronosyltransferase are members of an Ah receptor target gene battery. Alteration of expression of other networks of genes may be directly or indirectly regulated by the Ah receptor. Activation of the receptor by a ligand can result in endocrine and paracrine disturbances and alterations in cell functions including growth and differentiation. Some of these effects have been observed both in humans and animals, suggesting the existence of common mechanisms of action.
Source & ©: WHO-IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 4
The source document for this Digest states:
The toxicokinetic determinants of dioxin and related chemicals depend on three major properties: lipophilicity, metabolism, and binding to CYP1A2 in the liver. Lipophilicity increases with more chlorination and controls absorption and tissue partitioning. metabolism is the rate-limiting step for elimination. The persistent compounds are slowly metabolized and eliminated, and therefore bioaccumulate. Induction of CYP1A2, which is partially under the control of the aryl hydrocarbon receptor (Ahr), leads to hepatic sequestration of TCDD. The structure/activity relationships for induction are different from that for binding to CYP1A2. Binding to this inducible hepatic protein results in non-linear dose dependent tissue distribution: as the dose increases, the relative concentration in extra-hepatic tissues decreases while that in liver increases. The induction of this protein occurs in both animals and people and results in a increase in the liver to fat ratio of these compounds. This effect has a minor impact on free TCDD and serum TCDD at the range of environmental exposure.
The basic determinants of pharmacokinetic behaviour are similar in animals and people. Several robust classical and physiologically based models have been used to describe the kinetic behaviour. They have contributed to the understanding that the apparent half-life is not absolute, but may vary with dose, body composition, age, and sex.
Given that these are persistent, bioacumulative compounds, what is the appropriate dose metric to use to equate risk across species? Free concentration in the target tissue would be the most appropriate measure. However, the body burden, which is highly correlated with tissue and serum concentration, integrates the differential half-lives between species. Much higher daily doses are required in rodents to achieve the same body burden, or tissue concentration, as a lower daily dose in people. Body burden is readily estimated in both people and rodents. Therefore, in order to compare risks between humans and animals, the body burden is the metric of choice. It is important to note that predictions of body burden based on lipid concentrations at high exposures may underestimate the total body burden and over- or underestimate specific tissue concentrations because of the hepatic sequestration. Use of PBPK models can readily allow for interconversion of body burden with tissue concentrations, as well as with daily dose. Less complicated models such as a steady state/ body burden models using first order kinetics will give approximately the same results at exposures in the environmental range.
There is a range of apparent half-lives for the various PCDDs, PCDFs, and dioxin-like PCBs. However, the TEQ is driven by a relatively small subset of these compounds. When background exposures are involved, an average half-life similar to that of TCDD may be used, but will underestimate daily exposure in short half-life chemicals and overestimate exposure for those with longer than average half-lives. However, if high levels of exposure are involved, such as in occupational settings, it is important to include the pharmacokinetic data on the individual chemicals.
Source & ©: WHO-IPCS
re-evaluation of the Tolerable Daily Intake (TDI) page 4-5
This summary is free and ad-free, as is all of our content. You can help us remain free and independant as well as to develop new ways to communicate science by becoming a Patron!
BECOME A PATRON!