Assessments based on common metrics
Risk-benefit assessments with common metrics include the use of single outcome measures, like incidences of mortality, morbidity, or exceeding/not meeting health-based guidance values. These types of assessments are easy to comprehend and have limited data needs, but they must be interpreted with caution because they usually only provide some of the information of interest (Fransen and others 2010). Further, many of these studies do not combine the risks and benefits into a net health outcome, as do composite metrics, but can be a useful step in a full risk-benefit analysis by presenting the information in the same units for comparison. Risk-benefit assessments that have been carried out for seafood using common metrics are reviewed in this section.
An early risk-benefit assessment of seafood by Anderson and Wiener (1995) used a risk tradeoff analysis method to compare the potential cancer risk of eating fish to the potential CHD risk of not eating fish. The cardiovascular risk of not eating fish was derived from the results of Kromhout and others (1985), described earlier, where consumption of 1 to 14 g fish/person/d was estimated to reduce the risk of CHD by 36% and consumption of 15 to 29 g fish/person/d was estimated to reduce the risk of CHD by 44%. The cancer-related risk of eating fish was estimated by calculating potential exposure to 6 carcinogenic compounds with an allowable concentration limit set by the FDA and a CSF determined by the EPA: PCBs, dioxins, dichlorodiphenyltrichloroethane (DDT), chlordane, dieldrin, and heptachlor. The analysis assumed that all fish consumed were contaminated with all 6 compounds at levels matching the FDA limits of 2.0 ppm (PCBs), 50 ppt (dioxins), 5.0 ppm (DDT), and 0.3 ppm (chlordane, dieldrin, and heptachlor). The CSFs associated with exposure to compounds at these levels were calculated, assuming an average body weight of 70 kg and chronic exposure over a 70-y lifespan. The results of this analysis revealed that the lifetime risk of getting cancer for someone eating 1 g of contaminated fish per day over the course of 70 y was estimated at 5.0 × 10−4 (5 in 10000) and consumption of 20 g of contaminated fish per day (1.4, 100-g servings/wk) for 70 y was estimated to increase cancer risk to 1 in 100. The overall risk for cancer for the average American is 25%, so based on these predictions consumption of 20 g/d of contaminated fish would increase the overall cancer risk to 26%. However, the cancer risk of eating 20-g fish/d in the United States based on the actual levels of contaminants in fish has been estimated to be much less (0.75 in 10000) than the risk of eating contaminated fish calculated using the previous assumptions (IOM 1991). On the other hand, at the time of this study the average total risk of CHD mortality was 35% and the average fish consumption was 15 g/d. The results of Kromhout and others indicated that reducing fish consumption from 15 to 29 g/d to 0 g/d would increase the risk of dying from CHD by about 66%, meaning that the total risk of dying from CHD would be predicted to increase from 35% to 58%. Based on the results presented here, the cardiovascular benefits of fish consumption were determined to far outweigh the carcinogenic risks, even when fish contain all 6 carcinogenic contaminants at the FDA limits and all cancers are assumed to be fatal.
Several studies have been carried out assessing the levels of organic contaminants in farmed and wild salmon and potential risks to human health (Hites and others 2004a; Hites and others 2004b; Foran and others 2005a; Huang and others 2006), with resulting recommendations to limit consumption of salmon to only 0.2 to 8 meals per month, depending on the harvest location. However, salmon is a rich source of omega-3 fatty acids and reducing consumption to these levels would be expected to concomitantly increase the risk of cardiovascular disease and mortality, as discussed above. To better understand the overall health effects of altering consumption levels of farmed and wild salmon, risk-benefit assessments have been conducted by Foran and others (2005b) and Dewailly and others (2007).
Foran and others (2005b) considered the cancer and noncancer risks associated with exposure to organic contaminants when enough salmon is consumed to provide 1 g of EPA + DHA per day. Levels of organic contaminants and omega-3 fatty acids in farmed Atlantic salmon and wild Pacific salmon were obtained from previous work (Hites and others 2004a). Risks were calculated based on an average body weight of 70 kg and continuous exposure to contaminants over a 70-y lifespan. Noncancer risk was calculated for 14 contaminants (including PCBs, hexachlorobenzene (HCB), chlordane, dieldrin, heptachlor, MeHg, and others) and was deemed acceptable when the ratio between the cumulative exposure level for all contaminants and the cumulative RfD for all contaminants was <1. The acceptable cancer risk level resulting from the cumulative analysis of 11 contaminants with CSFs (including PCBs, 2,3,7,8-TCDD, HCB, chlordane, dieldrin, heptachlor, and others) was set at 1 × 10−5, which is the midpoint of the acceptable range established by the EPA (1 × 10−4 to 1 × 10−6). At consumption levels of two 100-g servings per week, the cumulative noncancer risk from organic contaminants was predicted to remain within acceptable levels, with the greatest benefit coming from wild salmon. On the other hand, salmon consumption at these levels was associated with an increased cancer risk, with a cumulative risk of 8 × 10−5 (that is, 8 in 100000) for wild salmon and 2.4 × 10−4 for farmed salmon. Based on these results, Foran and others (2005b) made recommendations to limit consumption of farmed and wild salmon to 4 or fewer meals per month, depending on the source of the fish. However, when the health outcomes of consuming 1 g EPA + DHA per day were calculated, the number of lives that would be saved from CHD mortality was reported to be about 7100 per 100000 people, which outweighs the potential risk of cancer by a factor of 300 (farmed salmon) to 900 (wild salmon). Additional age-adjusted analysis by Mozaffarian and Rimm (2006) indicated that the CHD benefits outweigh the cancer risks by 100- to 370-fold for farmed salmon and 300- to more than 1000-fold for wild salmon. These factors may be further increased if salmon is consumed at levels that provide about 250 mg EPA + DHA/d (that is, about 150 g of wild salmon per week or 100 g of farmed salmon every 2 wk), which would be predicted to provide similar protection against CHD mortality as 1 g EPA + DHA/d while reducing lifetime cancer risk from salmon consumption by about 75%. Further, the levels of organic contaminants that form the basis of the risk calculations included skin and disregarded the losses of PCBs that can occur during cooking, so the actual risks of eating cooked salmon are predicted to be less than that calculated by Foran (Santerre 2010).
The CSF method used by Foran and others (2005b) to calculate cumulative cancer risk has been criticized as not being appropriate for the type of carcinogens found in salmon (that is, epigenetic carcinogens) because it assumes a linear, nonthreshold relationship between risk and low-dose exposure (Dewailly and others 2007). Instead, Dewailly and others used health-based guidance values for MeHg, PCBs, and dioxins to examine the reproductive and developmental risks associated with consumption of enough salmon to provide 500 mg EPA + DHA per day. Atlantic salmon and rainbow trout samples were collected in Quebec, Canada, and levels of contaminants and fatty acids were analyzed in skinless, raw fillets with all subcutaneous or mesenteric fat removed. The levels of EPA + DHA determined for farmed salmon in this study were about 4-fold less than those reported by Foran and others (2005b), and the results indicated that daily intake of 58 to 69 g (or four to five, 100-g servings per week) of farmed salmon or trout would provide 500 mg EPA + DHA. For risk-benefit assessment, the authors considered the contaminant exposure associated with consumption of two 180-g meals per week of farmed Atlantic salmon, which provides about 440 mg EPA + DHA/d. Calculations were carried out based on 20- to 39-y-old women with an average body weight of 60 kg. The predicted exposure to contaminants at this consumption rate was below the tolerable intakes established in Canada and by the FAO/WHO in all cases, with levels of 0.015 μg/kg bw/d for MeHg, 0.012 μg/kg bw/d for PCBs, and 0.070 pg TEQ/kg bw/d. Although not all dl PCBs were measured in this study, total TEQ intake was estimated to be 0.28 pg TEQ/kg bw/d, which was based on the assumption that dioxins make up about 25% of the total TEQ exposure. This predicted exposure level is well below the FAO/WHO tolerable intake of 2.33 pg TEQ/kg body wt/d. Farmed trout showed similar (for MeHg) or lower (for PCBs or dioxins) levels of contaminants as compared to farmed salmon and consumption of 360 g/wk would not be expected to result in excessive exposure. Overall, the authors concluded that two 180-g meals per week of farmed salmon or trout available in North American markets would be expected to provide sufficient levels of EPA + DHA without concern over the putative health risks.
Combining exposure assessments with health-based guidance values. A number of studies have assessed the risks and benefits of seafood by comparing exposure assessments with health-based guidance values for seafood (for example, TDI, RfD, or recommended intake). Although this type of study does not allow for a full quantitative risk-benefit assessment, it can serve as a valuable first step in identifying whether a complete assessment is warranted (Fransen and others 2010). These studies are generally carried out using either a deterministic (“worst case” scenario) or probabilistic approach (Cardoso and others 2010). The latter approach allows for an estimate of the probability of the target population that is at risk of either exceeding a maximum safe limit or not reaching a recommended intake level. The modeling of probability distributions takes into account the variability of the data and this approach has been increasingly used to assess contaminants in foods. It is important to note that probability estimates are highly dependent on the tail behavior of the distributions, since health-based guidance values tend to be at the upper or lower range of most individual intakes, and the statistical tools used for these assessments must be highly rigorous and reliable (Cardoso and others 2010). Some important variables to take into account in both deterministic and probabilistic studies are the food intake data and the levels of contaminants and nutrients in these foods. Food intake data are generally obtained through food consumption surveys such as food frequency questionnaires, 24-h recall dietary surveys, and one- to seven-day food diaries (Barlow and others 2010), while contaminants and nutrients in foods are generally obtained through databases, such as the one described by Sioen and others (2007a) which pools data from different publications. However, seafood is a complex food group with many different categories and species, and food intake data are generally not specific with regard to the seafood species consumed. Because various seafood species are known to contain different levels of nutrients and contaminants, exposure levels estimated for seafood in these types of assessments may be associated with a high degree of uncertainty. Studies that have compared exposure assessments with health-based guidance values to assess risks and benefits have been carried out specifically for consumers in countries such as France (Crépet and others 2005; Leblanc and others 2006; Verger and others 2008; Pouzaud and others 2009), Spain (Domingo and others 2007a), The Netherlands (van der Voet and others 2007), and Belgium (Sioen and others 2008), as well as on a broader scale for consumers across Europe (Cardoso and others 2010) and worldwide (Sioen and others 2009).
Several studies have been devoted to risk-benefit assessments for French consumers living in coastal regions with high fish consumption. One such assessment, called the CALIPSO study, was delegated by the General Food Directorate to the French Institute for Agronomy Research (INRA) (Leblanc and others 2006). The CALIPSO study examined dietary patterns among some 1000 French consumers living in 4 coastal regions with high seafood consumption, evaluated blood and urinary biomarkers associated with nutrient and contaminant intake for about half of the study participants, and determined levels of nutrients (omega-3 fatty acids) and contaminants (6 trace elements and 3 categories of POPs) in a variety of seafood sampled in the study regions. The study participants were limited to adults that consumed seafood at least twice per week and consumption data were obtained with a food frequency questionnaire that listed 82 fishes, mollusks, crustaceans, and seafood-based dishes. Omega-3 fatty acid intakes were compared to the French Recommended Daily Allowance (RDA) of 400 to 500 mg/d for adults and exposure levels to trace elements and POPs were compared to provisional tolerable intakes established by the JECFA, when available. The results indicated that consumption of at least 2 servings of fish, including some oily fish, per week would allow consumers to obtain the RDA of omega-3 fatty acids. Male and female study participants in the age range of 18 to 64 y consumed a weekly average of about 630 to 640 g of fresh and frozen fish, 260 to 270 g of mollusks and crustaceans, and about 270 to 310 g of other types of seafood, making total seafood consumption equivalent to about twelve, 100-g servings per week. EPA + DHA intake exceeded 500 mg/d for 84% of the study participants, with an average level of 1240 ± 960 mg/d (Bemrah and others 2008). However, most of the types of seafood that contributed strongly to omega-3 fatty acid intake also accounted for greatest exposure to POPs, particularly salmon, mackerel, and sardine. In terms of risks, the study found that only individuals in the highest consumption group had a nonnegligible risk of exceeding the maximum limits for MeHg, Cd, dioxins, and PCBs. The average exposure to POPs among all study participants was 18.7 ± 19.6 pg TEQ/kg bw/wk for dioxins and dl PCBs, 0.04 ± 0.06 μg/kg bw/wk for iPCBs, and 2.2 ± 1.8 ng/kg bw/d for PBDEs. Study participants had a 39% probability of exceeding the provisional tolerable weekly intake (PTWI) for dioxins and dl PCBs and 72% probability of exceeding the PTWI for iPCBs. The average exposure level to MeHg from seafood was 1.5 ± 1.2 MeHg/kg bw/wk, with some 34% of the study participants exceeding the PTWI established by JECFA (1.6 μg MeHg/kg bw/wk). None of the study participants exceeded the PTWIs established for organic tin, arsenic, and lead, and only 8.5% exceeded that established for Cd. In terms of blood levels of these trace elements, most subjects (94% to 97%) had levels at or below the standard level, and women of childbearing age had average MeHg levels of 2.3 to 3.4 μg/L, which is well below the highest exposure level at which adverse effects do not occur to the fetus (56 μg/L). Even individuals consuming up to 4.5 kg seafood per week with predicted exposure levels of 9.6 μg/kg bw/wk had maximum blood MeHg levels of 18 μg/L. When blood levels were converted to weekly exposure for women of childbearing age, the data indicated an average exposure of 0.4 ± 0.3 μg/kg bw/wk, as compared to a predicted average exposure of 1.3 ± 0.9 μg/kg bw/wk based on consumption and contamination data for the same group of women. Overall, based on the study results, the authors concluded that the general population should consume at least 2 servings of fish, especially oily fish, per week and pregnant and nursing women should limit consumption of predatory fish to once per week.
Other studies conducted among French consumers have reported that women of childbearing age had a 3% to 5% probability of exceeding the PTWI for MeHg, based on data from exposure assessments (Crépet and others 2005; Verger and others 2007). In order to examine methods for reducing MeHg exposure, Crépet and others (2005) assessed the probabilistic effects of 5 different risk management scenarios (assuming 100% compliance): (1) no change in consumption patterns, (2) remove all predatory fish above 1.0 ppm MeHg and all other fish above 0.5 ppm MeHg from the market, (3) remove all fish exceeding 0.5 ppm MeHg from the market, (4) remove 12 species of predatory fish from the market, or (5) restrict consumption of predatory fish to an exact number of portions per week. Current fish consumption and exposure levels were obtained from a previous survey (French INCA survey) that used a 7-d food log obtained from a nationally representative sample of the French population. Crépet and others (2005) utilized data from 1945 male and female adults and 848 children within this data set, combined with mercury levels reported in previous studies for 89 individual seafood items. Average consumption of seafood varied for each age group, with children consuming 174 g/wk and adults consuming 285 g/wk. Mean body weights were 19 kg for children ages 3 to 6 y, 29 kg for children ages 7 to 10 y, and 58 kg for women of childbearing age. Based on these data, under scenario 1 the probability of exceeding the PTWI for MeHg was 4.4% for women of childbearing age and 6.7% for children (12.6% for ages 3 to 6 y; 5.0% for ages 7 to 10 y). Scenarios 2 and 3 did not significantly reduce exposure levels among children, but scenario 3 (removing all fish above 0.5 ppm) did significantly reduce probability of MeHg exposure among women of childbearing age to 0.6%. In scenario 4, where 12 predatory species are removed from the market, the authors reported significant reductions in MeHg exposure for women of childbearing age (0% probability of exceeding the PTWI for MeHg) and children ages 3 to 6 y (2.8% probability), but not among children aged 7 to 10 y (1.5% probability). Under scenario 5, the authors suggested an exact number of portions of predatory fish per week that would allow target groups to remain under the PTWI for MeHg. For example, a recommendation that women of childbearing age limit consumption to two, 170-g portions (or 340 g) of predatory fish per week or to 255 g per week if also consuming nonpredatory fish. Overall, the authors suggested that risk management options that provide advice on food consumption, such as scenario 5, are more efficient compared to additional restrictions for MeHg levels in fish. However, a later study examining the effects of a risk-benefit advisory among French consumers reported that the advisory did not lead to a decrease in predatory fish consumption, but it did result in a significant decrease in overall fish consumption (Verger and others 2007).
A subsequent study compared the exposure levels of PCBs and dioxins to intake levels of omega-3 fatty acids among 401 French fish consumers in western coastal areas (Verger and others 2008). The consumption data used in this study were obtained previously in the fish advisory study, which utilized a 1-mo food diary detailing types and frequency of seafood consumed for 195 men and 206 women (Verger and others 2007). The men had an average body weight of 75 kg and ate seafood 3.3 times per week, while the women had an average body weight of 62 kg and ate seafood 2.9 times per week. Exposure levels were calculated using data from the French Ministry of Agriculture and Fisheries. Overall, 20% to 30% of the target population was estimated to exceed the PTWI established by the Scientific Committee on Food (SCF) for dioxins and dl PCBs of 14 pg TEQ/kg bw/wk. About 25% of the total exposure was from PCDDs and PCDFs and the remaining 75% was from dl PCBs. On the benefit side, about 60% of the target population obtained the recommended intake of 500 mg/d long-chain omega-3 fatty acids. When risks and benefits were compared, only 41% of the study participants had an optimal balance of meeting the RDA of omega-3 fatty acids while remaining below the PTWI for dioxins and dl PCBs: 19% of individuals met the RDA but exceeded the PTWI, while another 38% of individuals were below the PTWI but were also below the RDA. The authors concluded that consuming the RDA for omega-3s of 500 mg/d through seafood consumption was compatible with the threshold for dioxins and dl PCBs, but that consumers with omega-3 intakes above 1500 mg/d from seafood consumption were likely to also be exceeding the PTWI for dioxins and dl PCBs.
Pouzaud and others (2009) assessed seafood consumption patterns and intake of MeHg and omega-3 fatty acids among 161 pregnant French women living in a coastal region with high-fish consumption. The authors used the food frequency questionnaire from the CALIPSO study to obtain seafood consumption data for women at both 12 and 32 wk of pregnancy. Portion sizes were estimated based on a catalog of photos presented to the study participant. At both time points, hair samples were obtained for MeHg testing and body weights were recorded. At week 12, participants had a mean seafood consumption of 322 g/wk and an average body weight of 60 kg, compared to a mean seafood consumption of 309 g/wk and average body weight of 73 kg at week 32. The mean dietary exposure to MeHg from seafood was not significantly different at the 2 time points, with an overall range of 0.6 to 0.7 μg/kg bw/wk. There was also no significant difference in the hair MeHg concentrations across the 2 time points, which ranged from 0.1 to 3.7 ppm, with a mean of 0.8 ppm. Overall, about 5% of the women were exceeding the PTWI for MeHg, similar to results of previous studies on women of childbearing age (Crépet and others 2005; Verger and others 2007), and about 50% of the women were not obtaining the RDA of 500 mg/d for long-chain omega-3 PUFAs. The authors used a cluster analysis tool to group the study participants into 5 different categories related to fish consumption and exposure levels, and found that only women consuming a high proportion of fatty fish meet the RDA for omega-3 fatty acids without exceeding the PTWI for MeHg.
Domingo and others (2007a) estimated dietary exposure to DHA + EPA and chemical contaminants among Spanish consumers. The authors measured fatty acids, metals (Hg, Cd, Pb), and organic pollutants (dioxins, dl PCBs, polybrominated diphenyl ethers (PBDEs), polychlorinated diphenyl ethers (PCDEs), HCB, polychlorinated naphthalene (PCNs), and (PAHs) in the edible portions of the top 14 species consumed in Spain. Daily consumption rates of these 14 species were calculated for a 70-kg male based on consumption data obtained previously and a standard meal size of 227 g. The average EPA + DHA intake was determined to be 244 mg/d, which is very close to the level recommended by FAO/WHO (250 mg/d). The estimated intakes of total Hg (0.14 μg/kg bw/d), Cd (0.02 μg/kg bw/d), and Pb (0.03 μg/kg bw/d) were all below the provisional tolerable intakes established by the FAO/WHO for these compounds (Table 2). When the correction factor of 0.85 is applied to the total Hg intake, the MeHg intake can be estimated at 0.12 μg/kg bw/d, which is below the PTWI but slightly above the RfD established by the U.S. EPA. The estimated intakes of dioxins and dl PCBs (0.54 pg TEQ/kg bw/d) as well as HCB (0.16 ng/kg bw/d) were all below the PTWIs established by FAO/WHO for noncarcinogenic effects. The total intake of 7 carcinogenic PAHs was associated with an increased cancer risk of 0.27 × 10−6 (that is, 2.7 incidences of cancer per 10000000 people) resulting from chronic exposure over a 70-y life span, based on EPA CSFs. Tolerable intake limits have not been established for PBDEs, PCDEs, and PCNs, which had estimated exposure levels of 0.30, 0.56, and 0.02 ng/kg bw/d, respectively. The authors did not report the percentage of the target population that may be at risk from excess exposure to contaminants or deficient intake of EPA + DHA. In order to help consumers remain below exposure limits for carcinogenic and noncarcinogenic effects, the authors developed recommended monthly fish consumption guidelines for the top 14 fish in Spain. They determined the greatest noncarcinogenic risk to be from MeHg exposure, and recommended limiting consumption of tuna to 2 meals per month and swordfish to 0.5 meals per month. The greatest carcinogenic risk was determined to be from PAHs and dioxins. To remain below PAH exposure limits, recommended consumption levels were calculated to be between 0.5 (clam/mussel/shrimp) and 4 (hake/red mullet/sole/cuttlefish/squid) meals per month, depending on the species. To remain below dioxin exposure limits recommended consumption levels were calculated to be between 1 (red mullet) and 16 (hake or cuttlefish) meals per month, depending on fish species. However, the authors did not compare the risks of reducing fish consumption to these levels in terms of the concomitant decreased intake of EPA + DHA that would occur and the subsequent increases in risk of cardiovascular disease and mortality. In a companion paper, Domingo and others (2007b) presented an interactive risk-benefit online tool that allows the consumer to input their weight, meal size, and consumption frequency in order to calculate their intake of EPA + DHA and exposure to metals and organic pollutants from the 14 seafood types examined above.
A study from The Netherlands reported the development of a probabilistic model to calculate simultaneous exposure to multiple compounds from food and to predict different dietary scenarios (van der Voet and others 2007). The model was used to assess long-term intake of EPA + DHA, dioxins, and dl PCBs from a total diet perspective, as well as predict the effects of replacing other types of food in the diet with seafood. Dietary patterns were derived from the Dutch National Food Consumption Survey of 1997/1998, in which body weight and food intake were recorded for 6250 Dutch individuals using a 2-d food diary that included amount and frequency of consumption. The authors considered 18 food types in the model, 11 of which were fish/shellfish, and combined levels of dioxins, dl PCBs, and EPA + DHA in these foods with the dietary information to estimate total intake of these compounds. In order to compare the FAO/WHO TDI for dioxins and dl PCBs with the Health Council of The Netherlands adequate intake (AI) for EPA + DHA (450 mg/d), the AI was expressed in terms of body weight for a 65-kg individual (7 mg/kg bw/d). Based on 500 random samples from 10000 Monte Carlo simulations, the results of the dietary analysis showed that in most cases (98% to 99%) the EPA + DHA intake was below the body weight-adjusted AI and the dioxin and dl PCB exposure was below the TDI established by FAO/WHO. Only about 2% of the population was above the body weight-adjusted AI and below the TDI for dioxins and dl PCBs. In addition to calculating the percentage of the sample population that is meeting health-based guidelines, the authors also examined the probable effects of replacing beef and pork consumption with salmon, eel, or a mixture of fatty fish (salmon, eel, herring, and mackerel) at levels of 10%, 25%, 50%, and 100%. The base rate for frequency of fatty fish consumption reported in the food diaries was 5.3%, compared to 68% for beef, 74% for pork, and 27% for chicken. Overall, the best scenario in terms of meeting health-based guidance values was found to be substitution with 10% to 25% salmon or a mix of fatty fish. At higher percentages (50% to 100%), there was a lower frequency of maintaining dioxin and dl PCB levels below the TDI. At 10% replacement with these fish categories, about 50% of the population reached the AI for EPA +DHA and only 1.3% of the population exceeded the dioxin and dl PCB limit, whereas at 25% replacement, more than 90% of the sample population was able to reach the AI for EPA + DHA, while less than 5% were predicted to exceed the limits for dioxins and dl PCBs. On the other hand, substitution of beef and pork with 25% eel was predicted to result in about 99% of the population reaching the AI, but also about 11% would be exceeding the TDI for dioxins and dl PCBs. The authors pointed out that this analysis was meant to illustrate the use of the statistical model, and that a more complete analysis should be carried out that considers uncertainties, alternative data sets, and additional dietary scenarios. The use of a total diet model, as presented here, allows for a better overall picture of the dietary intake of certain compounds and food replacement scenarios may be useful in developing risk management and communication strategies.
Risk-benefit assessment in Belgium was carried out by Sioen and others (2008) using a probabilistic model to assess simultaneous exposure to PBDEs and omega-3 fatty acids exclusively due to fish consumption. Consumption data for some 800 Belgian fish consumers representative of the Belgian adult population with respect to age and region was obtained from a SEAFOODplus food frequency questionnaire in 2004 and body weights were incorporated based on previously determined age and sex distributions for the Belgian population. These individuals consumed an average of 216 ± 204 g seafood per week, as compared to the general Belgian population, which consumes an average of 168 g/wk. Based on a 100 to 150 g serving size, these levels are similar to the recommendations of the Belgian Health Council to consume fish 1 to 2 times per week. Levels of EPA + DHA and PBDEs were obtained for 10 fish commonly available on the Belgian market (for example, cod, salmon, tuna, saithe, and sole) using previously published data and exposure levels for 4 different dietary scenarios were calculated: (1) base consumption (216 g/wk of a variety of 10 fish), (2) consumption of 150 g/wk of cod (lean fish) and 150 g/wk of salmon (fatty fish), (3) consumption of 300 g/wk salmon, and (4) consumption of 150 g/wk salmon and 150 g/wk herring (also a fatty fish). Monte Carlo simulations were used to estimate the variability of the intakes in terms of consumption, body weight, and concentration of the contaminants and nutrients in fish. EPA + DHA intake was adjusted for body weight and was compared to a health-based guidance value of 9.7 mg/kg bw/d (derived from a dietary reference intake of 681 mg/d for a 70-kg individual consuming 2046 kcal/d). The results of the analysis revealed that scenario 1 was associated with the lowest mean intakes of both EPA + DHA (3.54 mg/kg bw/d) and PBDEs (0.85 ng/kg bw/d), while consumption of 2 servings per week of salmon in scenario 3 allowed for the highest ratio of EPA + DHA (11.9 mg/kg bw/d) to PBDEs (1.28 ng/kg bw/d). The replacement of 1 serving of salmon with herring in scenario 4 also provided elevated levels of EPA + DHA (9.6 mg/kg bw/d) compared to scenarios 1 and 2, but led to slightly higher intake of PBDE (2.4 ng/kg bw/d). While there is no established tolerable intake for PBDEs, the lowest observed adverse effect level associated with this group of compounds has been reported to be 0.6 mg/kg bw for the penta-BDEs (Darnerud 2003; Siddiqi and others 2003). Overall, increased fish consumption was associated with increased intake of EPA + DHA and PBDEs, with the greatest benefit: risk ratio being from consumption of 2 servings of salmon per week.
In a subsequent study, Sioen and others (2009) used the probabilistic approach described above to assess exposure to several nutrients (EPA + DHA, vitamin D, iodine) and contaminants (MeHg, iPCBs, dioxins + dl PCBs) on a global scale. The authors used consumption data for 7 different seafood categories gathered by the Global Environment Monitoring System (WHO 2007), which reports average food consumption for 13 regional "cluster" diets representing 183 countries worldwide. General levels of nutrients and contaminants were obtained from databases developed in previous studies (Sioen and others 2007a, b) and an intake assessment was performed for all 13 cluster diets with probability distributions fitted for each seafood category, nutrient, and contaminant. Exposure levels were based on the general adult population, with a mean body weight of 60 kg for most regions and 55 kg for individuals from Asian countries. The highest seafood intake was reported for Cluster L, which included Japan, Korea, Philippines, Madagascar, and others, with 69.0 g/person/d, followed by Cluster F (the Nordic-Baltic countries; 49.2 g/person/d), and Cluster G (Afghanistan, China, India, Thailand, and others; 45.0 g/person/d). The 2 clusters with the highest seafood intake had the highest intakes of EPA + DHA (400 to 600 mg/person/d), iodine (30 to 40 μg/person/d), and vitamin D (3 to 4 μg/person/d). Differences in the dietary patterns between regions were reflected in the types of contaminants present: Clusters L and F consume relatively high levels of pelagic fish and had the highest exposure to MeHg (about 200 to 300 ng/kg bw/d), whereas Cluster G, which consumed a greater proportion of freshwater fish, cephalopods, crustaceans, and mollusks, had lower exposure to MeHg (about 100 ng/kg bw/d) but the highest exposure to iPCBs (about 60 ng/kg bw/d) and dioxins + dl PCBs (about 3.3 pg TEQ/kg bw/d). In order to combine data for nutrients and contaminants, the intake of EPA + DHA was divided by the dietary reference intake (DRI) of 500 mg/d and graphed against the exposure to either MeHg or dioxins + dl PCBs divided by the TDIs established by the JECFA. These plots revealed that most clusters were not exposed to contaminants above the tolerable exposure levels; however, they also were not obtaining sufficient EPA + DHA to meet the DRI, with intake levels of about 100 to 300 mg/d. The only cluster diet (Cluster L) that obtained 500 mg/d of EPA + DHA also exceeded the TDIs for MeHg and dioxins + dl PCBs. Cluster G exceeded the TDI for dioxins + dl PCBs and had a daily EPA + DHA intake of about 200 to 300 mg, while cluster F was just below the DRI for EPA + DHA and had exposure at levels around the TDIs for both MeHg and dioxins + dl PCBs. When the authors compared the mean exposure levels for each cluster to the tolerable intakes for MeHg and dioxins + dl PCBs established by the Scientific Advisory Committee on Nutrition/Committee on Toxicity out of the United Kingdom (SACN/COT) to protect against nondevelopmental health problems (Table 2), none of the clusters exceeded the guidance values. There are several uncertainties of this study that could influence the estimated nutrient and contaminant exposure levels. For example, food consumption data were gathered by dividing food availability for a given country by the total population and it tends to overestimate consumption by about 15%. Also, the nutrient and contaminant data were based on seafood tested in Europe or North America and do not represent regional seafood consumed by some cluster diets. In conclusion, the authors noted that the benefits outweigh the risks of seafood consumption when the focus is on nondevelopmental effects and they called for a more in-depth international study that would include local nutrient and contaminant concentration data.
Cardoso and others (2010) examined seafood consumption patterns across 8 European countries (Germany, France, United Kingdom, Italy, Spain, The Netherlands, Portugal, and Iceland) and calculated the probability of exceeding the tolerable intake for MeHg or being deficient in EPA + DHA for consumers in each country. The authors took into account the 5 most-consumed types of seafood for each country and calculated per capita weekly consumption, assuming that two-thirds of the seafood weight was edible and average body weight was 60 kg. Because detailed consumption surveys were not used, log-normal distributions were constructed to reflect seafood consumption patterns among different consumers, including individuals that do not regularly eat seafood, and the values of each distribution curve were randomly sampled using a sample size of 10000 with the Monte Carlo method. As was the case with Sioen and others (2009), the nutrient and contaminant data were not representative of the entire study population, but rather were based on seafood collected in Portugal. The probabilities of exceeding the weekly reference intakes for MeHg and EPA + DHA from consumption of each seafood species were calculated using a tail-estimation estimator for most cases and a plug-in estimator for the few cases with high probabilities. Total per capita seafood consumption for the 8 countries ranged from 140 g/wk in the United Kingdom to 630 g/wk in Iceland, while consumption of the top 5 species examined in this study for each country ranged from 80 g/wk in the United Kingdom to 390 g/wk in Iceland. Based on total seafood consumption, the probability of exceeding 500 mg/d of EPA + DHA was estimated at 0.3% for the United Kingdom, 2.0% for Italy, 12.4% for Germany and The Netherlands, 20.3% to 24.2% for France and Iceland, 61.1% for Spain, and 66.0% for Portugal. Although Spain and Portugal consume less per capita seafood (210 and 290 g/wk, respectively) than Iceland, these 2 countries include sardines among the top 5 species, which are a rich source of EPA + DHA. The probability of exceeding the PTWI established by JECFA for MeHg based on total seafood consumption was below 5% for most countries and reached 6.7% for Portugal and 9.6% for Iceland. Among the top 5 fish consumed in Iceland, the highest probabilities of exceeding the PTWI for MeHg based on a single fish species were with tuna (0.50%) and haddock (0.34%), which had consumption levels of 69 and 158 g/person/wk, respectively. However, exceeding the PTWI based on exclusive consumption of either of these fish would require about five 100-g servings of tuna per week (7 times the current consumption levels) or fourteen 100-g servings of haddock (9.2 times the current consumption levels). The results of this study highlight the fact that selecting fish high in EPA + DHA and low in MeHg will improve the benefit:risk ratio related to seafood consumption.
Assessments using combined risk-benefit dose-response models. In 2009, the U.S. FDA issued 2 draft reports examining the health outcomes of seafood consumption with the purpose of providing additional scientific information to help address concerns over risks and benefits of commercial seafood in the United States (FDA 2009a, b). In one report, the beneficial effects of seafood consumption and omega-3 fatty acids for certain neurodevelopmental and cardiovascular endpoints were summarized (FDA 2009b) and in the other report, a quantitative risk-benefit assessment was conducted for seafood consumption (FDA 2009a). The risk-benefit assessment was focused on 3 health endpoints: (1) fetal neurodevelopment, (2) risk of fatal CHD, and (3) risk of fatal stroke. The consideration of both the benefits and the risks of seafood in the same quantitative analysis was a novel approach for the FDA, which has historically focused on quantifying the risk but not the countervailing benefits of a particular food. Current levels of U.S. fish consumption (that is, amounts and species) were estimated based on 3 sources of data: a 3-d food survey conducted by the U.S. Department of Agriculture between 1989 and 1991 (USDA 1993), the 30-d National Health and Nutrition Examination Survey (NHANES) conducted in 2001 to 2002 (CDC 2004), and market share data on consumable commercial fish in 2005 from the National Marine Fisheries Service (NMFS). This information was combined with MeHg concentrations in different fish species, as reported by FDA, EPA, and NMFS, to calculate current levels of MeHg exposure from fish consumption. The negative effects of MeHg on fetal neurodevelopment were modeled based on verbal development measurements primarily in children from the Iraq MeHg wheat poisoning event (Marsh and others 1987), with some data from the Seychelles Islands study (Myers and others 1995), while dose-response relationships regarding the positive effects of fish consumption were modeled using data from the UK cognitive development study (Daniels and others 2004). The effects of prenatal MeHg exposure and fish consumption were combined to estimate a net effect of IQ size equivalents in offspring using several hypothetical dietary scenarios involving women of childbearing age (15 to 45 y). IQ size equivalents are IQ points based on Z-Score conversions, which are statistical tools that measure the size of an effect and facilitate the comparison of results from different models. At current consumption levels (about 5% of women eating ≥340 g of fish/week, 95% of women eating <340 g/wk), there is an estimated net neurodevelopmental benefit equivalent to 0.225 IQ point per child, with 99% of the population likely to have a net benefit on IQ size equivalents (in excess of 1 IQ point per child for about 5% of population), 0.9% of the population likely to have no net effect, and 0.1% of the population likely to experience a net negative effect, equivalent to about 0.04 IQ point. In a scenario where women do not change their current consumption amounts, but instead eat only fish low in MeHg (≤0.12 ppm), an increase equivalent to 0.02 IQ point was predicted. Another scenario in which 100% of women were eating exactly 340 g of fish per week resulted in a net benefit equivalent to 0.57 IQ point. On the other hand, if women that are currently eating more than 340 g/wk were to decrease their consumption to this level, a net decrease equivalent to IQ point of 0.01 was predicted. Overall, these results indicate the greatest net neurodevelopmental benefit for pregnant women with increased fish consumption, especially fish that are low in MeHg.
Cardiovascular effects in the FDA risk-benefit assessment (FDA 2009a) were assessed using 2 types of models (meta-analysis and pooled analysis) that were developed based on studies that reported the effects of fish consumption, but not omega-3 fatty acids or MeHg, on CHD or stroke fatalities. The CHD meta-analysis model was based on the meta-analysis conducted by He and others (2004b), while the CHD-pooled analysis model included the studies in this meta-analysis as well as 3 additional studies published later (Folsom and Demissie 2004; Nakamura and others 2005; Iso and others 2006). The stroke meta-analysis model was based on another meta-analysis conducted by Bouzan and others (2005). The stroke-pooled analysis model utilized this meta-analysis as well as studies by Mozaffarian and others (2005), Nakamura and others (2005), and 3 additional studies that were analyzed by He and others (2004a). Based on the central estimates of these models, current levels of fish consumption were estimated to be averting approximately 31000 (meta-analysis model) to 40000 (pooled analysis model) deaths per year from CHD and approximately 22000 (meta-analysis) to 25000 (pooled analysis) deaths per year from stroke. Results of dietary scenarios suggested that if all women of childbearing age ate 340 g of fish per week, there would be a predicted decrease of approximately 250 (meta-analyses) to 340 (pooled analyses) deaths per year from CHD and stroke. If there were a 10% decrease in the amount of fish consumed by adult men and older women (> 46 y), there would be a predicted increase of approximately 3500 (pooled analyses) to 4000 (meta-analyses) deaths per year from CHD and stroke; and if all adult men and women were to increase their fish consumption by 50%, there would be a predicted decrease of approximately 11000 (pooled analyses) to 18000 (meta-analyses) deaths per year from CHD and stroke. However, it should be noted that the confidence intervals for the pooled analyses models are, by design, wider than those of the meta-analyses models and therefore they did include a small possibility that current fish consumption is associated with deaths in each age/gender category. Nevertheless, the bulk of the probability distribution did indicate a beneficial effect of fish consumption, making it more likely than not that increased fish consumption leads to a decrease in cardiovascular mortality.
The approach of combining the risks and benefits into a net health effect for a given endpoint was also used in a study examining potential development of species-specific fish consumption advice (Ginsberg and Toal 2009). The concentrations of MeHg and omega-3 fatty acids in 16 species of fish commonly available in the state of Connecticut, U.S.A, were used to predict the developmental and cardiovascular health effects associated with each fish. The cardiovascular dose-response relationship was developed based on the results of Guallar and others (2002), who found that the relative risk for a 1st myocardial infarction increased by 23% per 1 ppm hair mercury and on the findings of Mozaffarian and Rimm (2006), which showed that increasing EPA + DHA intake from 100 to 250 mg/d was associated with a 14.6% decrease in the risk of CHD death. Although these endpoints are a measure of cardiovascular health and they were compared equally in this risk-benefit assessment, CHD mortality includes sudden death and death from myocardial infarction, whereas a first myocardial infarction is not necessarily fatal. The dose-response relationship for neurodevelopmental health was based on the study of Oken and others (2005), who reported a 2.0-point increase in infant visual recognition memory (VRM) score per 100 mg fish oil/d and a 7.5-point decrease in VRM score per 1 ppm hair mercury. However, it should be noted that Oken and others (2005) only observed adverse effects among participants that had hair mercury levels above 1.2 ppm, and the maximum level of hair mercury reported was 2.4 ppm. Interestingly, Ginsberg and Toal (2009) incorporated a threshold of 0.51 ppm hair mercury into the cardiovascular dose-response model as the level below which no adverse effects were evident, but the hair mercury threshold for adverse cognitive effects observed by Oken and others (2005) was not incorporated into the neurodevelopmental dose-response model. The level of mercury exposure resulting from consumption of one 170-g meal was calculated for each fish species and then converted to hair mercury concentration using a one-compartment model (Rice and others 2003). The results showed that when one to two, 170-g meals per week are consumed, the estimated cardiovascular benefits from omega-3 fatty acids outweigh the risks from MeHg for all species except shark, swordfish, and yellowfin tuna. On the other hand, one 170-g meal per week from 9 out of the 16 fish examined was predicted to result in adverse neurodevelopmental effects, even for some low-mercury fish like cod (0.11 ppm) and canned light tuna (0.12 ppm). This is likely due to the relatively low levels of omega-3 fatty acids in these fish and the fact that the hair mercury threshold level for adverse cognitive effects was not incorporated into the model. Consumption of these 9 fish at this level would not be expected to exceed the RfD established by EPA. As expected, low-mercury fish with high levels of omega-3 fatty acids, such as salmon, trout, and herring, exhibited the greatest net benefits to neurodevelopment. The authors used the results of the risk-benefit assessments and acceptable body burdens based on the RfD to suggest species-specific fish consumption advisories. For example, for individuals concerned with neurodevelopmental effects, the authors recommended unlimited consumption (up to one, 170-g meal per day) for 7 of the fish species; limited consumption of canned light tuna and cod (two, 170-g meals per week), limited consumption of 4 other species (that is, canned white tuna, tuna steak, halibut, sea bass, and lobster) to just one, 170-g meal per week, and complete avoidance of shark and swordfish. However, the authors note that the focus of this study was to present a framework for risk-benefit assessment and the uncertainties in the dose-response relationships presented here make the conclusions tentative.
Assessments based on composite metrics
Composite metrics allow for the integration of risks and benefits for multiple health endpoints into a single net health impact. These assessments can combine 2 or more types of common metrics, such as mortality, morbidity, or disease incidence, to quantify the cumulative effect on health. Most studies assessing the risks and benefits of seafood with composite metrics have utilized the QALYs to express the net health outcome (Ponce and others 2000; Cohen and others 2005a; Guevel and others 2008), and 1 study used a monetary value based on standard EPA health benefit transfer figures (Shimshack and Ward 2010). These studies are reviewed here.
Studies using QALYs. The earliest publication that applied QALYs to risk-benefit assessment of seafood was presented by Ponce and others (2000). Benefits of fish consumption were defined as a decrease in myocardial infarction mortality and the risks were defined as neurodevelopmental delays associated with prenatal MeHg exposure. The benefit to dose-response relationship for fish consumption was modeled by logistic regression from summary epidemiological data collected for an adult male population in Chicago, IL (U.S.A.), over a 30-y period, which found an inverse relationship between fish consumption and the risk of death from CHD, especially nonsudden death from myocardial infarction (MI) (Daviglus and others 1997). A Weibul excess risk model was used to develop a dose-response relationship for risks using data on delayed talking incidence among children in Iraq with gestational exposure to contaminated grain (Marsh and others 1987). Fish consumption was examined over a range of intakes (0 to 300 g/d) and at a range of mercury concentrations (0.5 to 2.0 ppm). The net health impact of fish consumption was then calculated for 2 different population groups (n= 100000 individuals/population): (1) all members of a population and (2) women of childbearing age (defined by Ponce and others (2000) as 15 to 44 y) and their offspring. When myocardial infarction mortality was assumed to be equal in severity to delayed talking (that is, starting to talk at 24 mo of age), the net effect of consumption of two, 100-g servings of fish per week with mercury levels of 0.5 to 2.0 ppm was predicted to be positive for the total population (2000 to 5000 QALYs), but negative for the subpopulation of women of childbearing age and their offspring (−250 to 2000 QALYs). The maximum benefits occurred among the total population when more than ten, 100-g servings of fish with 0.5 ppm mercury were consumed per week, with a net gain of about 15000 QALYs. On the other hand, the subpopulation of women and children exhibited a net loss of 250 to 2000 QALYs for 2 servings of fish per week. When myocardial infarction mortality was weighted as more severe than delayed talking, two, 100-g servings of fish per week were linked to a net benefit of about 5000 QALYs for the total population, regardless of the mercury concentration in the fish (0.5 to 2.0 ppm). The results of unequal weighting were reported to continue to result in a net negative health impact for the subpopulation of women and children (QALYs not reported). However, the benefits of fish consumption to neurodevelopment, which would be expected to greatly improve the net health impact, were not considered in this model. Further, the mercury levels for fish used in this model were higher than those in most commonly consumed fish, which generally have concentrations of <0.05 to 0.35 ppm, with the exception of a few large predatory fish, such as swordfish, shark, and king mackerel (FDA 2009c). To improve future analyses, the authors suggested the inclusion of a greater number of health endpoints and scenarios comparing fish-based diets with other types of diets, as well as the substitution of fish with low MeHg levels.
To this regard, a comprehensive risk-benefit assessment was carried out for a range of fish consumption scenarios using composite metrics that incorporated dose-response relationships from 4 different studies (Cohen and others 2005a). An expert panel convened by the Harvard Center for Risk Analysis published a series of 4 papers developing dose-response relationships for fish consumption and CHD mortality (König and others 2005); fish consumption and stroke (Bouzan and others 2005); prenatal DHA intake and cognitive development (Cohen and others 2005b); and prenatal MeHg exposure and cognitive development (Cohen and others 2005c). The dose-response relationships were only developed for health endpoints that were expected to be substantially affected by changes in fish consumption and for which there were sufficient data for a quantitative analysis. In the study determining a relationship between fish consumption and heart disease mortality, including CHD and nonfatal MI, the authors identified 7 observational studies (Kromhout and others 1985; Ascherio and others 1995; Daviglus and others 1997; Albert and others 1998; Oomen and others 2000; Hu and others 2002; Mozaffarian and others 2002) of individuals with no pre-existing CHD for use in the dose-response analysis (König and others 2005). To develop a dose-response relationship between fish consumption and stroke risk, the authors combined relative risk results from 6 studies (5 prospective cohort studies and 1 case-controlled study) (Gillum and others 1996; Orencia and others 1996; Iso and others 2001; Caicoya 2002; He and others 2002; Bouzan and others 2005). The dose-response relationship between prenatal intake of n-3 PUFAs and cognitive development utilized 8 randomized control trials (RCTs) (Agostoni and others 1997; Willatts and others 1998; Lucas and others 1999; Birch and others 2000; Makrides and others 2000; Auestad and others 2001, 2003; Helland and others 2003) comparing cognitive development for children or mothers receiving n-3 PUFA supplementation (Cohen and others 2005b). The dose-response relationship between prenatal MeHg and cognitive effects was determined by aggregating results from 3 major epidemiology studies conducted in the Faroe Islands, Seychelles Islands, and New Zealand (Cohen and others 2005c). The dose-response relationships developed in these studies were then used to calculate the net public health impact of fish consumption patterns related to risk-benefit advisories. The impacts of changes in fish consumption on MeHg exposure, omega-3 fatty acid intake, and servings of fish per week were estimated using a modified version of a previously developed exposure assessment model (Carrington and Bolger 2002; Carrington and others 2004). This model assumes that 10% to 20% of the population does not eat fish, and therefore health impacts due to changes in fish consumption are assumed to affect 85% of the population. Consumption rates for 42 types of fish were estimated using data from the USDA Continuing Survey of Food Intake by Individuals (CSFII) (USDA 1998) and NHANES data from 1999 to 2000 (CDC 2003). Levels of MeHg in fish were obtained from the FDA and NMFS and levels of omega-3 fatty acids were derived from the USDA Agricultural Research Service Nutrient Data Laboratory (http://www.nal.usda.gov/fnic/foodcomp/search/). The average maternal body weight was estimated at 60 kg and the baseline fish consumption was 18.7 g/d (130 g/wk) for women of childbearing age (15 to 44 y) and 23.1 g/d (160 g/wk) for other population members ≥15 y of age. The public health impacts of 5 dietary scenarios were compared to the baseline fish consumption for the U.S. population: (1) women of childbearing age maintain current amounts of fish consumption, but only eat fish with mercury levels ≤ 0.13 ppm, (2) women of childbearing age decrease total fish consumption by 17%, regardless of mercury content, (3) in addition to women of childbearing age, other members of the population also reduce fish consumption by 17%, (4) all females not of childbearing age and all males increase fish consumption by 50%, and (5) all adult females (including those of childbearing age) and males increase fish consumption by 50%. When women of childbearing age maintained current consumption levels but only ate fish lower in mercury (scenario 1), a net benefit of 49000 QALYs per year was predicted for the total population, primarily due to the cognitive benefits of DHA, which would contribute an average of 0.1 IQ point per child born. Scenario 2 was based on a study that reported a 17% decrease in overall fish consumption by pregnant women following the 2001 FDA advisory (Oken and others 2003). This dietary scenario was associated with a substantially smaller net benefit to health as compared with scenario 1, with + 0.02 IQ point per child and a net impact of 9700 QALYs per year. In scenario 3, where all members of the population decrease fish consumption by 17%, the net health impact was negative (−41000 QALYs per year), with the greatest losses experienced by elderly males (ages 75 to 84), whose annual CHD mortality risk would be increased by about 2 in 10000. On the other hand, the greatest net benefit to health (+120000 QALYs per year) occurred in scenario 4 when fish consumption was increased by 50% among all females not of childbearing age and all males, with a reduced risk for CHD mortality of 5 in 10000 among elderly men. In the case where all adult males and females increased fish consumption by 50%, the total benefits were offset slightly by the negative impact from MeHg on cognitive development (−0.07 IQ point/child), with a net health impact of +90000 QALYs per year. The effects of POPs were not considered in this risk-benefit assessment because they were not expected to be major contributors to the net health impact; for example, a sample calculation for scenario 4 based on the data reported by Hites and others (2004a) showed that exposure to organic contaminants was associated with a loss of about 600 QALYs per year, compared to the net benefits of 120000 QALYs per year. The overall results of this risk-benefit assessment suggest the importance of fish consumption in terms of the net health impact for the total population. When comparing the predicted results of scenarios 1 and 2, the importance of correctly following advisories for women of childbearing age to consume low-mercury fish, but not reduce total fish consumption is also apparent. The results of scenario 3, where the total population reduces fish consumption, indicate the potential for substantial reductions in public health and increased risks of CHD mortality when advisories targeted at a specific population inadvertently discourage fish consumption among other population groups.
Guevel and others (2008) utilized a QALY approach to assess the risks and benefits of high fish consumers in France. Consumption data for individuals consuming 2 or more servings of seafood per week were obtained from the CALIPSO study (Leblanc and others 2006; Bemrah-Aouachria and others 2008) and the most common types of fish and seafood were sampled locally and analyzed for fatty acids and MeHg. This information was combined to determine the exposure levels for these compounds among the target populations and then to compare risks and benefits for consumers with medium and high EPA + DHA intake. Consumers in the 1st quintile of the CALIPSO study (medium EPA + DHA intake) had an average fish consumption of 334 g/wk, an average EPA + DHA intake of 391 mg/d, and an estimated MeHg exposure of 0.8 μg/kg bw/wk. On the other hand, consumers in the 5th quintile (high EPA + DHA intake) consumed an average of 1104 g seafood/wk, with a daily EPA + DHA intake of 2700 mg and a weekly MeHg exposure of 2.6 μg/kg bw. The net QALYs associated with increasing EPA + DHA intake from medium to high levels were calculated for the adult population in France using dose-response curves developed previously linking fish consumption to cognitive and cardiovascular endpoints (Bouzan and others 2005; Cohen and others 2005a, b, c; König and others 2005). Additional dose-response curves linking EPA + DHA intake to the same cardiovascular endpoints were also developed by the authors based on previous studies (Dolecek and Grandits 1991; Iso and others 2001; He and others 2002; Hu and others 2002; Mozaffarian and others 2002). The net result of increasing EPA + DHA intake from 391 to 2700 mg/d was beneficial for both cognitive (+5949 QALYs) and cardiovascular endpoints (91229 to 114475 QALYs), regardless of the dose-response model. When all endpoints were combined, the total QALYs associated with increasing fish-derived EPA + DHA intake were 97248 using the EPA + DHA loglinear model developed by Guevel and others (2008); 116800 using the fish linear model from the Harvard Center for Risk Analysis (Cohen and others 2005a); and 285774 using the EPA + DHA exponential model developed by Guevel and others (2008). Despite the net benefits associated with increasing fish consumption and EPA + DHA intake, the potential effects of MeHg on neurodevelopment resulted in a negative lower bound of the 95% confidence intervals, ranging from −104380 QALYs for the EPA + DHA exponential model to −278665 for the EPA + DHA loglinear model. Overall, these results were in agreement with Cohen and others (2005a) that the benefits of fish consumption outweigh the risks; however, the magnitude of these effects is influenced by the type of dose-response curve utilized. Integration of additional risks and benefits into the QALY model was recommended for future studies on this topic.
Health-based monetary impacts. The use of monetary values to quantify risks and benefits of seafood consumption was explored in a study that considered the effects of mercury advisories on dietary patterns (Shimshack and Ward 2010). The dietary changes following the 2001 U.S. FDA advisory on mercury in seafood were examined using household-level seafood consumption data obtained from the Information Resources, Inc.'s InfoScan Consumer Network database. The data used by Shimshack and Ward were collected from close to 15000 consumers that were asked to scan the universal product codes for all products purchased from all stores upon returning home over a 3-y period (2000 to 2002). Changes in seafood types and amounts were investigated following the 2001 advisory for “at-risk” households with pregnant women, nursing women, or children under 6. Similar to the results reported by Oken and others (2003), a 17% decrease in fish consumption by pregnant women was observed following this advisory (Shimshack and Ward 2010). Of those who decreased their fish consumption, “at-risk” households decreased fish consumption 21.4% and there was a 60% increase in the number of consumers with no significant fish and shellfish consumption. Overall, there was no evidence of differential avoidance of high mercury fish, with at-risk groups reducing consumption of low-mercury seafood like salmon (27.9% reduction) and shrimp (17.5% reduction). Consumption of white tuna and light tuna fell by 14.0% and 19.5%, respectively. However, when education level was considered, households with a college degree did show selective avoidance of high-mercury fish, with an overall decrease in MeHg exposure of 27.9% (compared to 0.003% for less educated households), but there was also a substantial decrease of about 20% in the n-3 fatty acid intake among both education groups. The health impacts of these declines in seafood consumption were calculated using the cognitive and cardiovascular dose-response models developed previously (Bouzan and others 2005; Cohen and others 2005a, b, c; König and others 2005). However, rather than using a QALY approach, the net health impacts were expressed in terms of monetary values using U.S. EPA benefit transfer figures of $13084 per IQ point and $7.52 million for the value of statistical life, based on 2007 U.S. dollar amounts. Overall, the 21.4% reduction in seafood consumption following the 2001 U.S. FDA advisory was estimated to have a net health impact of U.S. −$30. Declines in MeHg exposure were associated with a benefit of +0.012 IQ points/child, while declines in the EPA + DHA intake were associated with −0.008 IQ points/child, resulting in a net benefit of 0.004 IQ points/child following the advisory (equivalent to U.S. $61). On the other hand, the decline in EPA + DHA intake was also associated with a net increase in CHD and stroke mortality of +0.63 deaths per 100000 adults (equivalent to U.S. −$91). The effects of an idealized scenario presented by Cohen and others (2005a; scenario 1), in which at-risk households maintain overall fish consumption amounts but only eat low-mercury fish, were also examined by Shimshack and Ward (2010) in terms of risks and benefits to neurodevelopment. This scenario resulted in a net benefit of 0.039 IQ points/child (U.S. $587). These results indicate the importance of targeted strategies for reducing MeHg exposure without concomitantly reducing n-3 fatty acid intake in order to receive the greatest health benefits from seafood.