Tributyltin in U.S. Market-Bought Seafood and Assessment of Human Health Risks

This study assessed potential human health risks posed by tributyltin in seafood purchased from U.S. seafood markets. In 1989 and 1990, samples of fish, bivalve molluscs and crustacea were purchased at local markets along the Atlantic, Gulf and Pacific coasts of the United States and along the Great Lakes (Lake Michigan). Samples were then analyzed for tributyltin, and the concentrations observed used to evaluate potential human health risks from consumption of market-bought seafood on the basis of available mammalian toxicology data. The assessment indicated health effects were unlikely from exposure to tributyltin in market-bought seafood during 1989 to 1990, shortly after peak tributyltin usage in antifoulant bottom paints on vessels in the United States.     

A Preliminary Human Health Risk Assessment of Organochlorine Pesticide Residues Associated with Aquatic Organisms from the Rangsit Agricultural Area,Central Thailand

Food consumption is one of the main routes of human exposure to organochlorine pesticide residues (OCPRs). To assess the potential health risks associated with OCPRs contaminants due to freshwater organism consumption, a number of vegetables, prawn, snail, and fish were collected from Khlong 7 (canal), Rangsit agricultural area, Pathum-Thani Province, Thailand. The samples were extracted using a multiresidue extraction method and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb) levels. Based on a plausible worst-case scenario, the local population could be at risk for cancer due to consumption of fish contaminated by α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, dieldrin, DDD, DDE, and DDT. Likewise, individuals may be at risk from consumption of Lanchester's freshwater prawn Macrobrachium lanchesteri, freshwater snail Filopaludina mertensi, swamp morning-glory Ipomomea aquatica, neptunia Neptunia oleracea, and water lily Nymphaea lotus because these species all contained elevated concentrations of α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, and dieldrin.     

Risk Assessment of Rotavirus Infection in Surface Seawater from Bohai Bay,China

Dose-response data indicate that rotavirus (RV) may be one of the more infective agents among enteric viruses. The major limitation at present in the assessment of infection from rotavirus is lack of quantitative data on viral infectivity. In this work, an integrated cell culture and real-time quantitative polymerase chain reaction (ICC-qPCR) method and a Beta-Poisson model for risk assessment were employed. A set of 28 surface seawater samples was collected from December 2010 to September 2011 in Bohai Bay, China, to enable a seasonal risk assessment of infective RV at recreational beaches. Thirty-two percent of the samples were positive for rotavirus, and the estimated concentration range of infectious human rotavirus was 1 to 279 PFU/L. We further confirmed that the contamination of seawater with rotavirus was higher in autumn and winter, which was in reasonable agreement with the trend observed in a prior epidemiological study. Our preliminary risk assessment indicated the daily risk of illness at almost all the contaminated sites exceeded an acceptable threshold of marine recreational water quality (19 illnesses per 1000 swimmers). The detection method and dose-response model in the current work appear useful for evaluating pathogenic risks of seawater to vacationers and can inform management actions.     

Human Exposure to Mercury Through Fish Consumption: Risk Assessment of Riverside Inhabitants of the Urrá Reservoir,Colombia

This study evaluated the risk to human health from mercury exposure through fish consumption in three riverside populations: Children (CH, 2–15 years old), women of childbearing age (WCHA, 16–49 years old), and the rest of the population (RP) from the Urrá reservoir area, Colombia. Questionnaire-based surveys were used to collect data and information about the weekly amount of fish consumed (WAFC) and the relative importance of each fish species in the diet of the study participants. There were no significant differences in WAFC between population groups. CH recorded the highest weekly intake of total Hg (WIT-Hg) (0.6–55.4 μg/kg bodyweight/week), with significant differences (p < .05) from WCHA (0.2–26.7 μg/kg bw/w) and RP (0.1–23.6 μg/kg bw/w). A high percentage (90%) of estimated WIT-Hg values exceeded the provisional tolerable weekly intake (PTWI) established in order to protect the embryo and fetus. Results suggested that sensitive subgroups, such as pregnant women or those who may become pregnant and young children should limit or avoid consumption of certain fish of higher trophic levels due to their high total Hg (T-Hg) concentrations (up to 2.73 μg/g). In sum, the high values of WIT-Hg in children and women of childbearing age revealed a worrying situation, which should be reviewed carefully in order to prevent a potential public health crisis.     

Pesticide handling practices,health risks,and determinants of safety behavior among Iranian apple farmers

Common safety practices in pesticide use were assessed among apple farmers in Ardabil Province, Iran. With reference to the place of storing pesticides, most farmers (60%) stated that they store the pesticides in stalls and warehouses, while 8.5% stated that they store the pesticides in their houses. The majority of the farmers (71.5%) stated that they prepare the pesticide sprays in the orchards or next to irrigation wells. Almost one out of three farmers (32.8 %) reported that they dump the empty containers in the orchard fields and almost an equal proportion (30.2%) reported that they usually bury the empty containers. Irritating (burning) eyes and blurred vision were symptoms that the majority of respondents had experienced. Most farmers used trousers, long-sleeved blouses/shirts, and gloves when spraying, but coveralls and goggles were rarely used. Age and farming experience negatively affected PPE use and safety behavior, namely old and experienced farmers did not follow safety rules. On the contrary, education, information about pesticides, and farming as the main profession promoted safety behavior. Overall, significant levels of exposure among farmers can be concluded due to pesticide use. The extension services should aim human safety in relation to pesticide use in agriculture.     

Risk Assessment for Dermal Exposure of Organochlorine Pesticides for Local Fishermen in the Rangsit Agricultural Area,Central Thailand

Organochlorine pesticides (OCPs) used in agriculture and for public health purposes were banned in Thailand over the past decade; however, their persistent residues have been found in several agricultural areas of the country. This may result in adverse effects to human populations. This study investigated the concentration of organochlorine pesticides residues (OCPRs) in surface water and evaluated the potential cancer risk associated with dermal contact of the local fisherman fishing in the Khlong 7 canal, Rangsit agricultural area, central Thailand. Water samples were extracted using liquid-liquid extraction (LLE) and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb or ng/ml) levels, that is, ∑ Endosulfan (α -, β -, and -sulfate) 0.082 ng/ml > DDT and derivatives 0.019 ng/ml > ∑ HCH (α -, γ -, β -, and δ -HCH) 0.014 ng/ml > aldrin and dieldrin 0.007 ng/ml > heptachlor and heptachlor epoxide 0.0068 ng/ml > endrin and endrin aldehyde 0.005 ng/ml > methoxychlor 0.001 ng/ml, respectively. Using the worst-case scenario defined as the reasonable maximum exposure (RME) to assess the potential cancer risk, five OCPs (dieldrin, 4,4′ -DDT, β -HCH, heptachlor, and heptachlor epoxide) may pose a risk of concern on a lifetime human carcinogenesis greater than one in a million.     

Evaluating Human Risk from Exposure to Alkylated PAHs in an Aquatic System

Polycyclic aromatic hydrocarbons (PAHs) are a large class of organic chemicals typically found as mixtures in the aquatic environment from natural, petrogenic, and pyrogenic sources. People can be exposed to PAHs through ingestion or dermal contact with contaminated sediments or through ingestion of finfish and shellfish exposed to contaminated sediments. Although more than 100 PAHs have been identified, human exposure and risk are commonly evaluated for 18 individual PAHs. Other PAHs, such as alkylated PAHs, likely contribute to biological activity of environmental PAH mixtures; however, insufficient toxicity data are available to quantify their potential risk. This article presents an initial evaluation of the potential for human health risk from exposure to alkylated PAHs in sediment and fish. Individual alkylated PAHs have been observed to have potentially mutagenic, tumor-promoting, or carcinogenic activity. However, except for 1-and 2-methylnaphthalene, insufficient toxicity data are available to quantify toxicity or cancer risk from exposure to individual alkylated PAHs or mixtures of alkylated PAHs. This article describes a proposed strategy to better understand the potential human health risk from exposure to alkylated PAHs. Implementation of this strategy will contribute to evaluations of human exposure to complex PAH mixtures in the environment.     

Human Health Risk from Metals in Fish from Saudi Arabia: Consumption Patterns for Some Species Exceed Allowable Limits

Fish are a healthful source of protein, but contaminants in some fish pose a risk. While there are multiple risk assessments from Europe and North America, there are far fewer for other parts of the world. We examined the risks from mercury, arsenic, lead, and other metals in fish consumed by people in Jeddah area, Saudi Arabia, using site-specific data on consumption patterns and metal levels in fish. The U.S. Environmental Protection Agency's Hazard Quotient (HQ) and cumulative Hazard Index (HI) for non-cancer endpoints and Carcinogenic Index for cancer were used to determine the health risk based on fish consumption rates. Of the 13 fish species examined, HQ was greater than 1 (indicating elevated risk) in two species for arsenic, and seven species for methylmercury. The cumulative HI for all metals was above 1 for all but three species of fish at the mean consumption rates. Generally, fish species with HI above 1 for one sampling location, had HI above 1 for all sampling locations. The implications of these findings are discussed in the light of strategies for reducing risk from fish consumption while encouraging dietary intakes of fish with low mercury and arsenic levels.     

Bioaccumulation of heavy metals in tissues of selected fish species from Ganga river,India, and risk assessment for human health

The study measured the concentration of Cd, Cr, Pb, Cu, and Zn in various fish tissues (muscle, gills, and liver) of 18 fish species (C. gachua, C. marulius, C. punctatus, C. nama, C. ranga, H. fossilis, C. batrachus, P. ticto, P. phutunio, L. rohita, L. calbasu, L. gonius, T. putitora, T. tor, R. rita, G. chapra, H. ilisa, and N. botia) collected from Ganga river. It is the survey regarding metal concentration in fish tissues increasing day by day. The metal concentration in different fish tissues varied on the following range: Cu (0.45–8.54 µg/g wet wt), Zn (0.07–2.2 µg/g wet wt), Pb (0.20–2.62 µg/g wet wt), Cd (0.07–2.32 µg/g wet wt), and Cr (0.09–1.74 µg/g wet wt). The results show the concentration of Pb, Cd, and Cr metals to be higher than internationally recommended standard limits (as determined by the WHO and FAO) and other similar studies. Generally, higher concentrations of metals were found in liver and gills than muscles. Despite lower estimated daily intake (EDI) of fish in the area (per recommended daily allowance guidelines), values of daily average consumption were lower than the recommended values by FAO/WHO/EFSA, and in fish samples these were below the provisional permissible levels for human consumption. The continuous exposure to heavy metals has been linked to the development of mental retardation, kidney damage, various cancers, and even death in instances of very high exposure in human body.     

A Deterministic Method for Deriving Site-Specific Human Health Assessment Criteria for Contaminants in Soil

A method for deriving Site-Specific Assessment Criteria (SSAC) for use when considering risk to human health from chronic exposure to heavy metals (except lead), metalloids, and organic substances in soil, with application to the United Kingdom (UK), is described. The SSAC represents the soil concentration above which an unacceptable risk to human health may be indicated.

The method considers the UK standard land uses (residential with and without plant uptake, allotment gardens, and commercial/industrial) by applying the default exposure factors and algorithms provided. Non-standard land uses can be also considered. Site-specific determinations of contaminant bioaccessibility or of plant-to-soil concentration factors may be used if available.

The method adopts the risk-based source-pathway-receptor pollutant linkage framework and a deterministic methodology. Exposure pathways considered are direct ingestion of soil and dust, consumption of home grown or allotment vegetables, ingestion of soil attached to such vegetables, inhalation of soil vapors outdoors and inhalation of soil vapors indoors. A test for the significance of the dermal pathway is also included.

It is not intended that the method be used to generate or replace UK Soil Guideline Values, because this can only be done by the appropriate authoritative bodies within the UK (Department of the Environment, Food and Rural Affairs and the Environment Agency).     

Estimation of Mercury Intake from Selected Fish Species Commercialized in Alexandria,Southeastern Mediterranean Sea,Egypt

Total Hg concentrations were determined in muscle tissue of some fishes with different feeding habits (12 fish species) obtained from the main fishing locations along the Alexandria coast, a region particularly impacted by historic industrial Hg activities. Health risks to human via dietary intake of the edible portion of fish were assessed by the target hazard quotients (THQs). Mercury maximum concentrations corresponding to fish muscle tissue were found in L. mormyrus, S. rivulatus, and S. luridus (3.56, 2.94, and 1.35 μg g^?1 wet weight, respectively). Thence most of these three species bass (75% of L. mormyrus, 76% of S. rivulatus, and 54% of S. luridus) were greater than a 0.47 μg g^?1 threshold corresponding to a 1 meal per month consumption limit. M. cephalus, S. aurita, S. chrysotaenia, B. boops, and A. djedaba bass (100%) were less than a 0.12 μg g^?1 threshold corresponding to a 4 meals per month safe consumption limit. Mercury THQs values, ranging from 0.11–1.76, were of concern. In particular, the health risk was mainly ascribed to consumption of S. rivulatus (1.72) and L. mormyrus (1.76), although also the TEQs values caused by consuming S. luridus (0.64) were rather high, being close to 1.     

Risk Assessment of Some PCDDs,PCDFs, Dioxin-Like PCBs,and PCBs in Contaminated Dairy Products: An Egyptian Pilot Case Study

Samples of butter, cream, and white cheese were collected from the city of Ismailia, Egypt, and analyzed for polychloro dibenzo-p-dioxins, pentachloro dibenzo-p-furans, and dioxin-like polychlorinated biphenyl, PCBs. Butter samples had the highest mean content of PCDD/F and dioxin-like PCBs. Butter samples were the most contaminated samples in all dairy products analyzed in this study, whereas white cheese samples were the least contaminated. The spectrum of congeners detected in butter and cream were similar, with all congeners at detectable levels, whereas the spectrum of congeners detected in white cheese differed, with some congeners, namely 1,2,3,4,7,8-Hexa CDD, 1,2,3,4,6,7,8-Hepta CDD, and 1,2,3,7,8,9-Hexa CDD below WHO TE toxicity levels. 1,2,3,7,7-PeCDD, with its high concentration, was the principal contributor to the TEQ intake in both cream and butter samples. Similarly, the high concentration of 2,3,4,7,8-PeCDF in cream, butter, and white cheese samples was the main factor contributing to their TEQ intake. Estimated intakes of PCDDs/Fs were 129.2, 115.8, and 51.25 pg WHO-TEQ/day for butter, cream, and white cheese, respectively. Taking into account the sum of PCDDs/Fs and dioxin-like PCBs, estimated intakes were, 171.7, 155.8, and 68 pg WHO-TEQ/day, for butter, cream, and white cheese, respectively. Assuming an average bodyweight of 60 kg (WHO-TEQ/kg), these levels correspond to bodyweight-normalized intake levels of .15, 2.92 and 0.95 pg WHO-TEQ/kg/day.     

Applying USEPA Risk Assessment Guidance in the 90s

Over the past decade, risk assessment has become increasingly relied upon for helping to make environmental management decisions. This trend has been accompanied by research and refinements in basic risk assessment methodologies to improve our ability to understand and evaluate the human health risks associated with chemical exposures.Despite this progress, significant uncertainties continue to be associated with the risk assessment process. These uncertainties typically derive from gaps in available data regarding chemical toxicity, and from difficulties in reliably estimating the magnitude of chemical exposures. Given these limitations, risk assessment is generally most valuable in evaluating relative risk; for example, when comparing alternatives to achieving a specified goal, setting priorities for protecting human health, or establishing procedures for properly allocating resources. Risk assessment can also be useful for developing regulatory benchmarks such as permit limits for air or water. In many cases, however, the limitations of the risk assessment process make it difficult (if not impossible) to reliably estimate an absolute level of risk, especially for a specific individual in an exposed population. In such cases, risk assessment can be seriously misapplied, and its results misinterpreted.This paper discusses some of the challenges that have been faced by the field of risk assessment during the 1990s. Current trends in risk assessment, and its use by regulatory agencies in making risk management decisions, are also described.     

沈阳某冶炼厂废弃厂区的人类健康风险评价

以沈阳某冶炼厂废弃厂区重金属污染监测为依据,采用美国环保局最新的人类健康风险评价标准方法对沈阳某冶炼厂废弃地块污染土壤进行了评价,并且假设未来该土地利用类型为工业用地(Ⅰ)或休闲用地(Ⅱ).评价结果显示:工业用地(Ⅰ)和休闲用地(Ⅱ)的累积非致癌风险指数分别为2.65×10-2和3.67×10-2;工业用地(Ⅰ)和休闲用地(Ⅱ)由呼吸摄入Cd造成的潜在致癌风险指数分别为4.48×10-9和7.30×10-10,不会对在该地区工作和休闲的人们造成身体健康上的伤害;无论是工业用地假设还是休闲用地假设,由无机铜造成的人类健康风险在整个风险中所占的比例最大;由美国环保局的人类健康风险评价方法反推得出的冶炼厂地块未来为工业用地的土壤修复目标值均小于我国工业企业土壤环境质量风险评价基准值.     

Seasonal variations of mercury levels and human health risk in vegetables from Arid Oasis (Shihezi city), Xinjiang,Northwest China

The purpose of this study was to investigate the seasonal variations of mercury levels and human health risk in vegetables that were collected from farmland, home garden, and plastic greenhouse in summer and winter 2016 in Arid Oasis (Shihezi city), Xinjiang, Northwest China. The results showed that the levels of mercury in fresh vegetables were lower in winter (0.003–0.025 mg·kg^?1) than in summer (0.001–0.035 mg·kg^?1). Single factor pollution (P) in vegetables indicated that all vegetables were polluted in diverse levels. The exceeding rate in different vegetables was 0.00% to 88.89% in summer and 0.00% to 100% in winter compared with limits of pollutants in vegetables. The value of bio-concentration factor (BCF) revealed that the mercury absorption capacity of 10 species vegetables decreased in the following order: pea seedling > spinage > caraway > lettuces > pakchoi > celery > crowndaisy chrysanthemum > chives > spinach > shallot. The daily intake (DI) and target hazard quotient (THQ) of mercury for children (2–12 years), young adults (18–45 years), and quinquagenarian (>45 years) indicated that non-carcinogenic values were below the threshold values except one sampling sit from farmland around the industrial parks. Furthermore, the THQ of open field in summer was higher than plastic greenhouse in winter. Under the same pollution level, children had more non-carcinogenic risk than young adults and quinquagenarian.     

Health outcomes of road-traffic pollution among exposed roadside workers in Rawalpindi City,Pakistan

To document ill-health effects of air pollution on the local inhabitants, we analyzed the self-reported health issues associated with the inhalation of road traffic on daily basis. For this purpose, a revised version of ALS-DLD-78S questionnaire was administered, comprising the personal information and details related to the clinical history of the surveyed population (i.e. n = 580). Five dependent (outcome) variables, including chest pain, redness of eyes, shortness of breath, eye-tearing, and skin-itching were taken into account. The results revealed that ～80% of the surveyed population were directly or indirectly exposed to road traffic, and the incidence of chest pain among exposed individuals was estimated to increase with age (odds ratio (OR) = 6.49; 95% confidence interval (CI) = 1.46–28.81), especially among cardiac patients (OR = 13.87; 95%-CI = 3.28–58.61). However, the shortness of breath was predominantly observed among those who reported to have asthmatic symptoms (OR = 32.84; 95%-CI = 15.59–69.15) and cardiovascular symptoms (OR = 13.8: 95%-CI = 3.63–52.41). In case of itching, the population along the roadside were more vulnerable to exposure (OR = 5.79; 95%-CI = 2.81–11.93). While, exposure to traffic exhaust could be attributed to ～3.13% rise in the incidences of redness of eyes among general population, the outcomes of this survey show that daily exposure to traffic pollution is an important health concern for the urban population in general, as well as for various occupational groups in particular, working in outdoor environment.     

Health Risk Assessment of Petrol Station Workers in the Inner City of Bangkok,Thailand, to the Exposure to BTEX and Carbonyl Compounds by Inhalation

The occupational health risk of petrol station workers from exposure to BTEX and carbonyl compounds via inhalation was estimated in the inner city of Bangkok. Personal sampling was performed within the workers’ breathing zone using 2,4 dinitrophenylhydrazine cartridges and charcoal glass tubes connected to a personal air pump during eight working hours at six petrol stations. BTEX and carbonyl compounds were quantitatively analyzed by GC/FID and HPLC/UV, respectively. Of all detectable BTEX and carbonyl compounds, the levels of the four most prevalent compounds (benzene, ethylbenzene, formaldehyde, and acetaldehyde) were used to assess the lifetime cancer risk and 95% confidence interval of the risk levels were found to be totally higher than acceptable criteria for benzene (1.82 × 10^–4–2.50 × 10^–4), formaldehyde (7.81 × 10^–6–1.04 × 10^–5), ethylbenzene (4.11 × 10^–6–5.52 × 10^–6), and acetaldehyde (1.39 × 10^–6–2.45 × 10^–6). Thus, petrol station workers in the inner city of Bangkok have a potentially high cancer risk through inhalation exposure. With respect to the noncarcinogenic agents, toluene, m,p-xylene, o-xylene, and propionaldehyde, all non-cancer health risk were within hazard quotients of 1 and of acceptable risk.     

Monte Carlo Simulation-Based Health Risk Assessment of Heavy Metal Soil Pollution: A Case Study in the Qixia Mining Area,China

In recent years, heavy metal pollution accidents have occurred in many regions of China, and the public has become increasingly concerned about its health. Based on a U.S. Environmental Protection Agency model and using Monte Carlo simulation techniques, this article presents a procedure for health risk assessment of heavy metal pollution. A case study was conducted in the Qixia lead and zinc mining area. Based on the magnitude of heavy metal contamination in the mine factory, vicinal Qixia scenic site and village, the potential health risk calculated for a lifetime of exposure (through ingestion and dermal contact) was determined as the cumulative carcinogenic and non-carcinogenic risk for workers, tourists, and local residents (including children and adults), respectively. The risk assessment indicated that the carcinogenic risk is not significant. However, Pb poses a significant cumulative non-carcinogenic risk, which tends to be serious for workers. Additionally, local children are more vulnerable than adults to the risks associated with heavy metal contamination. Accordingly, risk alleviation and preventive measures should be taken, especially for children and workers.     

Characterization of Scale Abnormalities in Pinfish, Lagodon rhomboides, from Biscayne Bay, Florida

Correlations between marine habitat degradation and the prevalence of abnormalities and diseases in populations can provide a starting point for understanding the effects of changes in environmental conditions on marine organisms. The present study characterized the features of scale disorientation (SD), a common morphological anomaly encountered in pinfish, Lagodon rhomboides, in Biscayne Bay, Florida (U.S.A.). Scale disorientation consisted of discrete patches of scales rotated dorsally or ventrally away from the normal scale position without any projection of the scales outwards from the body surface. The direction of scale growth within the patches varied from normal to a minor misalignment to a complete reversal of direction. The severity of SD, defined as the percentage of body surface area affected, varied from 1 to 34% with a mean of 9.3%. Affected fish monitored in the laboratory demonstrated a proportional growth of SD areas such that the percentage of body surface affected did not change as the fish grew. Scale disorientation was more prevalent in the northern region of the bay, an area known to be more contaminated. Scales from SD areas exhibited significantly abnormal morphology with larger average focus diameter, smaller size, more elongate shape and fewer radii relative to normal scales. Experimental removal of scales demonstrated that normal scales regrew in normal orientation and morphology while those from SD areas regrew in abnormal orientations and morphologies. Experiments in which fish were exposed to acute and chronic injuries indicated that these physical traumas were insufficient to directly induce formation of scale disorientations typical of those seen in the wild. Observations of pinfish in the laboratory revealed that SD areas can appear spontaneously in normal juvenile and adult fish. These new SD areas developed relatively rapidly, did not require prior scale loss and remained stable in size after first appearance. Although the etiology of SD remains unknown, the significant difference in prevalence of this syndrome between regions of Biscayne Bay having different levels of sediment contaminants suggests that environmental factors may be important in development of SD.     

Extrapolation in Human Health and Ecological Risk Assessments: Proceedings of a Symposium

A symposium was conducted in April 1998 by the U.S. Environmental Protection Agency's National Health and Environmental Effects Research Laboratory (NHEERL) to explore issues of extrapolation in human health and ecological risk assessments. Over the course of three and one half days, leading health and ecology experts presented and discussed research methods and approaches for extrapolating data among taxa and across levels of biological organization, through time, and across spatial scales. The intended result of this symposium was enhanced interaction among a diverse array of scientists, policymakers, and risk assessors to promote identification of approaches for reducing the uncertainties of extrapolation in risk assessment.