Risk and Benefit Assessment of Potential Neurodevelopmental Effect

Article pubs.acs.org/JAFC

Risk and Benefit Assessment of Potential Neurodevelopmental Effect Resulting from Consumption of Marine Fish from a Coastal Archipelago in China Yi-Xiong Gao,†,‡ Hongxia Zhang,†,§ Xinwei Yu,∥ Jia-lu He,∥ Xiaohong Shang,*,† Xiaowei Li,† Yunfeng Zhao,† and Yongning Wu*,† †

China National Center for Food Safety Risk Assessment, Key Lab of Food Safety Risk Assessment, Ministry of Health, No. 7, Panjiayuan Nanli, Peking 100021, China ‡ National Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, No. 27, Nanwei Road, Peking 100050, China § School of Public Health, Shanxi Medical University, No. 56, Xinjiannan Road, Taiyuan 030001, China ∥ Zhoushan Center for Disease Prevention and Control, No. 268, Wengshan Road, Zhoushan 316021, China ABSTRACT: The aim of this study was to assess net neurodevelopmental effect via maternal consumption of marine fish. A total of thirty-one species were collected from Zhoushan, China. The net IQ point gain was assessed by FAO/WHO deterministic approach and probabilistic computation (if necessary). Results of the deterministic assessment of two samples belonging to Scoliodon sorrakowah showed negative IQ point gain in both common and extreme consumption scenarios (175 and 450 g/week, respectively); the net IQ gain caused by both consumption scenarios of other species were positive. Both consumption scenarios of Scoliodon sorrakowah showed beneficial neurodevelopmental effect according to probabilistic computation (95% CI for mean of net IQ gain: 0.0536−0.0554 and 0.1377−0.1425, respectively). Except for Scoliodon sorrakowah, this study indicates that both consumption scenarios of other studied species would be recommended according to the FAO/WHO approach. There would be no recommendation of consumption scenarios of Scoliodon sorrakowah for the reason for carefulness. KEYWORDS: marine fish, n-3 long chain polyunsaturated fatty acids, methylmercury, IQ point, risk−benefit assessment

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INTRODUCTION Though actual mechanisms of action of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are still unclear, these fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in development of the central nervous system (CNS) and the visual system in fetuses and children.1,2 CNS experiences a rapid development during the last trimester of pregnancy and postnatal months, with a large transportation of DHA to the brain.2 In contrast to the CNS, the visual system develops poorly prenatally and rapidly in the postnatal first year, which indicates that postnatal infant DHA intake, rather than maternal DHA status during pregnancy, would positively affect early visual development in infants.3,4 In fetuses, DHA is normally transferred by the placenta during the last trimester of pregnancy,5 and in exclusively breastfed infants, DHA is mainly from breast milk, because the endogenous synthesis of DHA in infants is quite limited.2 The content of n-3 LCPUFAs in cord blood and breast milk could be modified by maternal intake.6,7 Therefore, the maternal diet appeared to be a crucial factor in fetal and infantile neurodevelopment. Several perspective studies reported a positive relationship between maternal intake or concentration of n-3 LCPUFAs (particularly DHA) and mental development.8−10 Marine fish would be the main food source of DHA in some Chinese coastal regions,11 but fish consumption also would be © 2014 American Chemical Society

the major route by which the common population is exposed to some contaminants, such as methylmercury (MeHg),12 which is a known neurotoxicant with adverse effects on fetal and infantile cognitive development.13,14 It has been shown that maternal fish consumption could increase MeHg concentration in maternal and cord blood, and increase fetal exposure resulting in delayed neurodevelopment.15,16 Results from a cross-sectional survey showed that estimated intakes of DHA were strongly correlated with estimated Hg intake in the Inuit population, whose traditional foods mainly include marine mammals and fish.17 These indicate that maternal marine fish intake could result in both benefits of DHA and risks of MeHg on neurodevelopment of children. Therefore, a balanced benefit and risk assessment is required. FAO/WHO recognized the importance of the issue and held an expert consultation on risks and benefits of fish consumption in January 2010 in Rome, Italy.18 They developed a framework using children’s IQ as a common end point and concluded that benefits of EPA plus DHA intake usually outweighed risks of MeHg exposure. However, they recommended that regional specific data for MeHg and n-3 LCPUFA concentrations needed to be collected Received: Revised: Accepted: Published: 5207

January 21, 2014 May 8, 2014 May 13, 2014 May 13, 2014 dx.doi.org/10.1021/jf500343w | J. Agric. Food Chem. 2014, 62, 5207−5213

Journal of Agricultural and Food Chemistry

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Table 1. Sample Weight (kg) and Concentrations of n-3 LCPUFAs (mg/100 g Edible Part) and MeHg (μg/kg Edible Part) in Marine Fish from Zhoushana n-3 DPA

sample wt

EPA + DHA

MeHg

scientific name

mean

std

mean

std

mean

std

mean

std

Trichiurus lepturus Larimichthys polyactis Pampus argenteus Collichthys lucidus Hapaloyenys mucronatus Pampus chinensis Cynoglossus robustus Muraenesox bagio Conger myriaster Nibea albif lora Sebastiscus marmoratus Thamnaconus modestus Scomber japonicus Scomberomorus niphonius Ilisha elongata Argyrosomus argentatus Miichthys miiuy Scoliodon sorrakowah Sparus macrocephalus Harpadon nehereus Arius sinensis Raja porosa Mugil cephalus Lateolabrax maculatus Trachinotus ovatus Hexagrammos otakii Oplegnathus fasciatus Rhabdosargus sarba Seriola quinqueradiata Auxis thazard Coilia nasus

0.92 0.53 0.65 0.92 1.08 1.00 0.92 1.13 1.08 1.20 1.00 1.33 1.13 1.08 1.37 1.20 1.03 2.33 1.09 1.13 0.97 1.08 1.10 1.23 0.87 1.13 1.07 1.00 0.97 1.03 0.93

0.14 0.07 0.08 0.13 0.17 0.13 0.10 0.16 0.15 0.12 0.16 0.17 0.15 0.13 0.15 0.11 0.08 0.28 0.10 0.10 0.12 0.12 0.13 0.19 0.11 0.14 0.13 0.13 0.14 0.12 0.14

54.4 40.3 19.6 5.5 88.7 71.6 32.7 87.0 130.8 55.1 41.6 4.4 84.8 34.6 58.4 18.0 23.9 6.1 135.7 1.6 71.0 18.2 84.5 92.5 199.8 10.1 84.4 100.1 7.0 81.5 112.9

11.5 6.1 4.8 6.5 25.6 12.3 5.5 15.2 21.9 17.4 10.3 5.9 11.0 7.7 5.8 4.8 15.0 1.3 29.6 2.5 27.6 4.3 106.8 24.5 22.5 1.8 12.8 15.8 4.7 11.5 28.5

590.7 758.9 175.6 181.3 358.0 470.3 228.0 836.4 893.8 413.4 448.9 137.2 1251.4 520.9 733.1 205.4 453.6 75.5 678.8 189.7 533.7 123.6 266.3 858.5 891.0 379.8 469.8 568.1 96.0 2458.2 1186.2

57.2 110.8 28.8 37.1 105.8 93.2 37.3 175.7 124.0 73.0 98.6 40.1 146.5 94.0 42.8 41.4 60.3 12.7 142.0 32.5 172.5 36.8 268.0 230.3 110.8 24.6 20.6 96.8 4.2 395.1 142.7

22.8 15.9 18.8 12.2 56.3 22.4 27.2 34.8 40.6 36.2 39.6 17.2 16.4 27.4 36.5 62.7 16.2 166.6 30.5 14.1 58.4 47.6 7.7 21.0 24.1 20.6 27.7 48.0 28.6 122.8 14.9

3.1 2.7 2.7 0.8 4.1 3.7 13.1 6.0 5.2 3.2 7.2 2.0 1.9 2.7 6.7 3.1 1.7 29.4 3.8 4.4 4.8 4.7 5.3 2.8 4.6 1.8 5.7 3.8 1.3 4.9 7.8

a The data of n-3 DPA, EPA, and DHA of all studied species26 and the mean of MeHg concentration of majority studied species27 could be obtained from Chinese published articles.

separate plastic container, and was frozen immediately at −20 °C for further analysis. Sample Analysis. Total lipids were extracted from 2 g of thawed sample by 50 mL of chloroform−methanol (2:1, by volume21). The preparation of fatty acid methyl esters (FAME) was operated according to a method described previously.22 FAME was analyzed by gas chromatography. Heneicosanoic acid was used as internal standard. MeHg was extracted from 1 g of thawed sample, and the concentrations of MeHg were analyzed by a method published previously.23 Methodology of Assessment of Net Neurodevelopmental Effect. The benefit−risk assessment approach developed by FAO/ WHO18 was used. Equations for quantitative integration which focus on net IQ point gain are listed as follows, and the meanings of all parameters in eqs 1 and 2 are available in a published brochure:18

for regional specific assessment.18 The concentrations of specific fatty acids and total mercury in some Chinese marine/freshwater fish were reported,12,19 but there are clear location differences in MeHg concentrations and species differences in DHA concentrations in marine fish,20 and there is little information on assessment of net neurodevelopmental effect via maternal marine fish consumption in China. In response to this public health concern, we calculated and integrated benefits of DHA and risks of MeHg caused by maternal consumption of some edible marine fish farmed or grown in Zhoushan, southeast China, to assess the net neurodevelopmental effect of these species according to the aforementioned FAO/WHO approach.

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MATERIALS AND METHODS

Samples Collection and Preparation. Common edible marine fish were collected between September and October 2011 from Zhoushan archipelago, which is a major fish farming area in southeast China. A total of thirty-one species (6 samples/species, 1 individual fish/sample) were purchased from local piers or traditional markets. All fish samples were farmed or grew locally and were medium-sized (Table 1). Scientific names have been used to represent the species in this article. Edible parts of samples were prepared by collectors. The processed filet of each sample was homogenized and expressed directly into a

IQ point loss = [MeHg] × 100(x /7) ÷ 60 × 9.3 × (−0.18 or −0.7)

(1)

where −0.18 is the central estimate of IQ points gained per microgram per gram of hair mercury gained, and −0.7 is the upper-bound estimate of IQ points gained per microgram per gram of hair mercury gained.18 In our study we choose −0.7 for the reason of more conservative assessment. 5208

dx.doi.org/10.1021/jf500343w | J. Agric. Food Chem. 2014, 62, 5207−5213


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Table 2. Change of IQ Points via Common and Extreme Maternal Consumption Scenarios common consumption scenario IQ gain

IQ loss

extreme consumption scenario net IQ gain

IQ gain

IQ loss

net IQ gain

scientific name

mean

std

mean

std

mean

std

mean

std

mean

std

mean

std


4.0 5.0 1.2 1.2 2.4 3.2 1.5 5.2 5.6 2.8 3.0 0.9 5.8 3.5 4.9 1.4 3.0 0.5 4.5 1.3 3.6 0.8 1.8 5.2 5.7 2.5 3.1 3.8 0.6 5.8 5.8

0.4 0.7 0.2 0.2 0.7 0.6 0.2 0.9 0.4 0.5 0.7 0.3 0.0 0.6 0.3 0.3 0.4 0.1 0.9 0.2 1.2 0.2 1.8 0.7 0.3 0.2 0.1 0.6 0.0 0.0 0.0

0.1 0.0 0.1 0.0 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.1 0.1 0.2 0.0 0.5 0.1 0.0 0.2 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.3 0.0

0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

3.9 5.0 1.1 1.2 2.2 3.1 1.5 5.1 5.5 2.7 2.9 0.9 5.8 3.4 4.8 1.2 3.0 0.1 4.4 1.2 3.4 0.7 1.8 5.1 5.6 2.5 3.1 3.7 0.6 5.5 5.8

0.4 0.7 0.2 0.2 0.7 0.6 0.3 0.9 0.4 0.5 0.7 0.3 0.0 0.6 0.3 0.3 0.4 0.1 0.9 0.2 1.2 0.2 1.8 0.7 0.3 0.2 0.1 0.6 0.0 0.0 0.0

5.8 5.8 3.0 3.1 5.3 5.8 3.9 5.8 5.8 5.7 5.7 2.4 5.8 5.8 5.8 3.5 5.8 1.3 5.8 3.3 5.6 2.1 3.0 5.8 5.8 5.8 5.8 5.8 1.7 5.8 5.8

0.0 0.0 0.5 0.6 0.7 0.0 0.6 0.0 0.0 0.2 0.2 0.7 0.0 0.0 0.0 0.7 0.0 0.2 0.0 0.6 0.6 0.6 2.2 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0

0.2 0.1 0.1 0.1 0.4 0.2 0.2 0.2 0.3 0.3 0.3 0.1 0.1 0.2 0.3 0.4 0.1 1.2 0.2 0.1 0.4 0.3 0.1 0.1 0.2 0.1 0.2 0.3 0.2 0.9 0.1

0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1

5.6 5.7 2.9 3.0 4.9 5.6 3.7 5.6 5.5 5.5 5.4 2.2 5.7 5.6 5.5 3.1 5.7 0.1 5.6 3.2 5.2 1.8 3.0 5.7 5.6 5.7 5.6 5.5 1.5 4.9 5.7

0.0 0.0 0.5 0.6 0.6 0.0 0.7 0.0 0.0 0.2 0.2 0.7 0.0 0.0 0.0 0.7 0.0 0.3 0.0 0.6 0.5 0.6 2.2 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.1

were applied in equations, respectively, to represent the maternal common and extreme consumption scenarios of specific species. The joint FAO/WHO expert committee on food additives (JECFA) has established a provisional tolerable weekly intake (PTWI) of 1.6 μg/kg bw for MeHg.25 In our study, 60 kg was considered to be the body weight of a pregnant woman/mother,18,25 in order to determine if the calculated results of maternal weekly MeHg intake exceeded the PTWI. We used probabilistic computation to represent uncertainty of sample variations, if the calculated results of the FAO/WHO deterministic approach could not provide a clear dietary recommendation for some species. Monte Carlo simulation was applied in probabilistic computation for these species to generate probabilistic distribution for the net neurodevelopmental effect caused by quantified uncertainties. There would be an optimal number of weekly servings (i.e., “optimal x”) of specific species for neurodevelopment according to eq 3, because the maximum positive effect from intake of EPA plus DHA is definite (5.8 points18). The “optimal x” of specific species could be determined by the relationship between the value of “net IQ point gain” and x, on the premise that the “[EPA + DHA]” and “[MeHg]” were known in eq 3. If the value of “net IQ point gain” increases with the increment of x in eq 3, then the “optimal x” of the species would be the value of x, by which the calculated result of “IQ point gain” equals 5.8 points in eq 2; if the value of “net IQ point gain” decreases with the increment of x in eq 3, then the “optimal x” of the species would be zero, that is, no recommended consumption of the species. Statistical Analysis. Data are expressed as mean and standard deviation. Pearson correlation analysis was used to assess relationships

IQ point gain = [EPA + DHA] × 100 × 0.67 × (x /7) × 0.04 (2) The maximum IQ gain from maternal consumption of EPA plus DHA was estimated at 5.8 points, with no further benefits with increasing consumption thereafter.18 Combining eqs 1 and 2 then gives a relationship between net IQ point gain and specific species consumption due to MeHg and n-3 LCPUFA intake:

net IQ point gain = {[EPA + DHA] × 2.68 ÷ 7 − [MeHg] × 1.55}x

(3)

where [EPA + DHA] is the total concentration of EPA plus DHA in fish (mg/g); MeHg] is the concentration of methylmercury in fish (μg/g); and x is the number of maternal servings of fish per week (100 g/serving). We estimated maternal intake of EPA plus DHA and MeHg from specific species consumption by two possible consumption patterns. According to “2002 China National Nutrition and Health Survey” (2002 CNNHS), the mean value of fish intake (including marine fish and freshwater fish) in China was 24.8 g/standard man-day (i.e., about 175 g/week of fish consumption), but coastal Chinese appear to have much higher consumption of aquatic foods, especially marine fish. According to data from “2007 Chinese Total Diet Study”, people who live in Fujian province, which is a coastal province of southeast China, had the highest marine fish consumption among all studied provinces in China (64.47 g/day, i.e., about 450 g/week of marine fish consumption).24 Therefore, 175 and 450 g/week of filet consumption 5209



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between concentrations of total lipids and MeHg, and between concentrations of EPA plus DHA and MeHg. A value for p < 0.05 was considered to indicate statistical significance. All data analysis (including Monte Carlo simulation) was carried out by Statistical Analysis System 9.1 (SAS Institute Inc., Cary, NC, U.S.).

4.9 (Raja porosa) to 5.8 (Coilia nasus), and optimal weekly consumption of all species does not cause a PTWI-exceeded MeHg exposure (Table 4).

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Table 4. Weekly Optimal Maternal Consumption (g) and the Maximum IQ Point Gain and MeHg Exposure (μg/kg bw/ week) via Weekly Optimal Consumption of Specific Species

RESULTS The concentrations of total lipids, main LCPUFAs (in the form of mean and standard deviation), and MeHg (in form of mean) of species could be obtained from Chinese published articles.26,27 The standard deviation of MeHg of all species was never published before this article. The mean concentrations of EPA plus DHA (in the form of mg/100 g edible part) of all species ranged from 75.5 (Scoliodon sorrakowah) to 2458.2 (Auxis thazard); the mean concentrations of MeHg (in the form of μg/kg edible part) of all species ranged from 7.7 (Mugil cephalus) to 166.6 (Scoliodon sorrakowah). It is noteworthy that the concentrations of n-3 LCPUFAs of all species would increase by about 10% if n-3 LCPUFAs included n-3 docosapentaenoic acid (n-3 DPA) (Table 1). Obviously, the largest exposure of MeHg in this study would be found in extreme scenario consumers when they consumed the species with the highest concentration of MeHg (Scoliodon sorrakowah). The intake amount of MeHg in this maternal group (1.68 μg/kg bw/week) was slightly higher than the PTWI, when mean plus 1.96 standard deviations was considered to be the extreme MeHg concentration of the species. The extreme consumption scenario of other species and the common consumption scenario of all species could not result in a weekly MeHg intake over 1.0 μg/kg bw. Except for Scoliodon sorrakowah, both 175 and 450 g of other species weekly maternal consumption would result in a positive neurodevelopmental effect in terms of change of net IQ points (Table 2). Scoliodon sorrakowah would cause an unclear neurodevelopmental effect via both consumption scenarios: the calculated results of two samples belonging to this species showed negative net IQ point gain (−0.108 points and −0.076 points via common consumption scenario, −0.278 points and −0.195 points via extreme consumption scenario, respectively), and the net IQ point gain via both consumption scenarios of the other four samples belonging to this species were positive but the values were less than 0.5 points. Both consumption scenarios of Scoliodon sorrakowah would result in a net beneficial neurodevelopmental effect according to probabilistic computation based on 10000 times simulated sampling (Table 3).

weekly optimal consumption

scenario

times of simulated sampling

mean of net IQ point gain

lower 95% CI for mean

upper 95% CI for mean

common extreme

6 6

10000 10000

0.0545 0.1401

0.0536 0.1377

0.0554 0.1425

MeHg exposure

scientific name

mean

std

mean

std

mean

std


258.4 203.2 881.8 870.1 453.2 333.4 680.1 189.0 172.3 377.2 351.4 1173.7 122.4 299.4 207.2 758.3 339.1 0.0 231.5 821.1 320.0 1297.6 1175.5 187.0 172.0 400.2 323.0 272.8 1580.7 63.0 129.3

23.8 29.8 141.6 206.8 125.2 68.7 117.5 44.9 24.4 73.7 79.1 291.0 13.9 57.7 11.8 126.0 46.4 0.0 48.3 158.3 140.4 296.7 733.9 47.9 19.4 23.9 14.1 43.4 67.9 10.0 15.9

5.7 5.8 5.5 5.6 5.4 5.7 5.5 5.7 5.7 5.6 5.6 5.5 5.8 5.7 5.7 5.1 5.7 0.0 5.7 5.6 5.5 4.9 5.7 5.7 5.7 5.7 5.7 5.6 5.1 5.7 5.8

0.0 0.0 0.1 0.0 0.1 0.0 0.2 0.0 0.0 0.0 0.1 0.1 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.1 0.2 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

0.1 0.1 0.3 0.2 0.4 0.1 0.3 0.1 0.1 0.2 0.2 0.3 0.0 0.1 0.1 0.8 0.1 0.0 0.1 0.2 0.3 1.0 0.1 0.1 0.1 0.1 0.1 0.2 0.8 0.1 0.0

0.0 0.0 0.1 0.0 0.1 0.0 0.2 0.0 0.0 0.1 0.1 0.1 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.1 0.1 0.2 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

There was a positive relationship between concentrations of total lipids and specific n-3 LCPUFAs (n-3 DPA, EPA, and DHA),26 but no relationship between concentrations of total lipids and MeHg (r = 0.011, p = 0.880). There was also a positive relationship between concentrations of EPA plus DHA and MeHg in the studied samples, though the relationship appeared to be moderate (r = 0.200, p = 0.006).

Table 3. Results of Probabilistic Computation for Scoliodon sorrakowah sample size

max. IQ point gain

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DISCUSSION We have presented results on a benefit−risk assessment based on fish samples collected from a major fish farming area in southeast China, and found that there would be neurodevelopmental benefits when almost all species were consumed at either the common or extreme consumption scenario. As Zhoushan archipelago is a main fishing ground in China and it provides aquatic foods to the whole country, our results are likely applicable to a majority of the population in China. IQ score was also applied as a common metric in other studies which focused on risk−benefit analysis on child neurodevelopment, but methodologies of quantitative integra-

Net IQ point gain decreases with the increment of weekly servings of the two aforementioned samples belonging to Scoliodon sorrakowah. Therefore, the optimal weekly consumption (or “the optimal x”) of this species is zero for the reason of more conservative assessment. The optimal weekly consumption (g) of other species ranged from 63.0 (Auxis thazard) to 1580.7 (Seriola quinqueradiata). The maximum IQ point gain via other species optimal consumption ranged from 5210



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tion of net IQ point change varied.28−30 The physiologically based pharmacokinetic (PBPK) model and several epidemiological studies were applied by Zeilmaker et al. to estimate the relationship between maternal DHA/MeHg intake via specific species consumption and change of IQ score.28 The results of their study indicated that the adverse effect of MeHg outweighed the beneficial effect of DHA in a majority of studied species (about 30 species), except a few oily fish species. Our results are more optimistic, partially because of the generally lower concentration of MeHg in species of our study (the ranges of MeHg concentration were 7.7−166.6 μg/kg in 31 species of our study and 0.011−0.829 mg/kg in 31 species of their study, respectively). Moreover, maternal fish consumption in that study was considered as 100 g/day, which is relatively higher than the actual intake amount in Chinese maternal population. Net IQ loss/gain calculated based on quality adjusted life year (QALY) required some basic information on the target population, for example, number of births to women in a specific age group,29,30 which was difficult to obtain in some instances. “Visual response memory points” (VRM) was applied as a “tentative” common metric to assess in utero neurodevelopmental health end point by risk−benefit index (RBI) equation,31 but the results of wild fish consumption in Alaska calculated by the VRM-RBI equation indicated that it is “difficult to craft consistent consumption advice” because net effects of consumption of many species varied significantly among regions or studies within the same region.32 A minimum ratio of DHA intake to mercury exposure (“de minimus”, 17 mg of DHA to 1 μg of MeHg) was calculated according to the women’s minimum daily recommended intake of DHA (100 mg) and the reference dose for MeHg (RfD, 0.1 μg/kg bw/d, proposed by the US Environmental Protection Agency).33 When the ratio of DHA to MeHg in one species was higher than “de minimus”, a woman would meet the daily recommended intake for DHA while not exceeding the RfD for MeHg.33 There was application of this ratio to “illustrate which species may be most beneficial for consumption”.20 The upper limit for MeHg intake proposed by US Environmental Protection Agency appeared to be more conservative than by JECFA: according to the PTWI for MeHg, “de minimus” would be about 7.3 mg of DHA to 1 μg of MeHg. In consideration of different characteristics of studies mentioned above, we considered that the FAO/WHO approach would be most suitable for our data. We did not find a report about net neurodevelopmental effect of Western Pacific species consumption assessed by the FAO/WHO deterministic approach before this study. Consumption of fish at high trophic level would cause a significant negative neurodevelopmental effect, because of bioaccumulation of MeHg.28 That is in accordance with our data: the species with the highest MeHg concentration in our study (Scoliodon sorrakowah) would be the top species in the local food pyramid. Scoliodon sorrakowah also has the lowest EPA plus DHA concentration in our studied species. All of these would be reason why consumption of this species would have the lowest net IQ point gain. Though the results of probabilistic computation for this species were positive, we still do not consider that its consumption scenarios deserve to be recommended. After all, there were samples of this species that showed negative results, while all samples of other species can provide a net beneficial outcome according to deterministic computation, which indicates that there would be more risk when a sample of Scoliodon sorrakowah was consumed; in other

words, negative net IQ gain would be more likely to occur via both consumption scenarios of this species, at least compared with both consumption scenarios of other species. Moreover, the positive results of Scoliodon sorrakowah consumption scenarios obtained by probabilistic computation almost equal zero, which indicates that the net neurodevelopmental benefit of consumption scenarios of this species would be negligible. Though the net IQ point gain via optimal weekly consumption is maximal according to the FAO/WHO deterministic approach, it appears that the application of common or extreme consumption scenario is more practical than of optimal weekly consumption, because filet consumption of the two scenarios is quantitative, which means that recommendation of common or extreme consumption scenario is more feasible than of optimal weekly consumption, in addition to Scoliodon sorrakowah. In most instances, n-3 LCPUFAs refer to EPA and DHA, and according to FAO/WHO expert consultation, “EPA plus DHA data were used to represent LCn3PUFAs, because it was considered that the evidence in the literature was most robust for these specific fatty acids”.18 That means some other n-3 LCPUFAs and their beneficial effects would be omitted, for example, n-3 DPA, which would exert neuroprotective effects according to animal study and could be a precursor to synthesize DHA in vivo. 34 Our results showed that concentration of n-3 DPA provided about 10% of concentration of EPA plus DHA, which indicated that there would be underestimation about beneficial neurodevelopmental effect caused by both consumption scenarios when n-3 DPA in samples was ignored. However, the dose−response relationship between n-3 DPA and its biological effects would be uncertain, because “n-3 DPA has not been extensively studied”.34 Alpha linolenic acid (ALA) is the primary member of the n-3 PUFAs family, which is rich in some kinds of culinary oil such as rapeseed oil and soybean oil. ALA also could be a precursor to synthesize DHA in vivo.35 Study about fish-eaters and non-fisheaters (including meat-eaters, vegetarians, and vegans) showed that intake of n-3 LCPUFAs was much higher in fish-eaters but the differences of EPA and DHA concentrations in plasma of different dietary groups were “considerably smaller”, because precursor−product ratio of ALA to n-3 LCPUFAs would be greater in non-fish-eaters.36 Moreover, young women seem to be fairly efficient at converting ALA to DHA, compared with men.37 The efficient conversion capability of young women would be an important physiological compensative mechanism for meeting the development of fetus and neonate during pregnancy and lactation. Indeed, the high consumption of ALArich culinary oil such as rapeseed oil or soybean-salad oil by pregnant women in some regions of China could be a reason why the DHA concentrations of colostrum in these regions with different aquatic food consumption are more similar than the aquatic food consumption difference would indicate they might be.22 Consumption of culinary oil in the Chinese dietary pattern tends to be relatively high (data from 2002 CNNHS showed that a Chinese metropolitan consumed about 44 g of culinary oil per day), and ALA-rich vegetable oil seemed to be the main culinary oil in many regions of China according to 2002 CNNHS. Therefore, we consider that methodologies about assessment of neurodevelopment caused by maternal fish consumption would refer to the potential benefit of other n-3 LCPUFAs and the endogenous production of EPA and DHA to a greater extent, which would contribute to revise the 5211



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beneficial effects caused by marine fish derived EPA and DHA intake in assessment. Our analysis about net neurodevelopmental effect could be part of risk−benefit assessment of fish consumption. Besides neurodevelopmental benefit, n-3 LCPUFAs were also known as a beneficial factor to the adult cardiovascular system38 and immune system.39 Moreover, fish contain other contaminants, such as dioxin-like compounds (DLCs), which would cause cancers40 and diabetes41 and also be neurotoxic.42 The FAO/ WHO expert consultation also proposed equations to assess net change of mortality caused by DLCs and n-3 LCPUFA intake via fish consumption.18 A further risk−benefit assessment which refers to the net change of mortality would be considered if the DLC data of samples could be obtained. Besides IQ point change, there are still some other end points which were applied to assess adverse neurodevelopmental effect caused by prenatal MeHg exposure in cohort studies from Faroe Islands13,43 and Seychelles.44−46 Findings showed that impacts of prenatal MeHg exposure on these end points varied, but there would be little information about the impact of n-3 LCPUFAs on them, and they are not regarded as common metrics by which risks and benefits could be compared at present. However, a sustained concern on these end points would be worth considering. Even though the consumption amount of the general population was used to estimate the consumption amount of pregnant women/mothers, the error would not be significant as the majority of Chinese pregnant women/mothers usually share foods with their family members.11,22 There would be a high concentration of n-3 LCPUFAs in some species of shellfish,18 but the consumption mean of shellfish in the Chinese dietary pattern (4.8 g/standard man-day, according to 2002 CNNHS) would be negligible when compared with fish, though high consumption of shellfish was found in a few regions of China.24 Therefore, shellfish samples were not considered in our study. In summary, the current study indicates that there was no recommendation of maternal consumption scenarios of Scoliodon sorrakowah. Common and extreme maternal consumption scenarios of other studied species from Zhoushan would be beneficial to neurodevelopment, and both consumption scenarios of other species would deserve to be recommended according to calculated results of the FAO/ WHO assessment approach. The MeHg exposure via optimal weekly consumption of all studied species would not exceed the PTWI. More factors would deserve to be considered in future analysis.

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assistance in species identification. Professor Linmao Ma from China CDC provided assistance in use of SAS software. We thank all sample-collectors from Zhoushan CDC. Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Salem, N., Jr.; Litman, B.; Kim, H. Y.; Gawrisch, K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 2001, 36, 945−959. (2) Koletzko, B.; Lien, E.; Agostoni, C.; Böhles, H.; Campoy, C.; Cetin, I.; Decsi, T.; Dudenhausen, J. W.; Dupont, C.; Forsyth, S.; Hoesli, I.; Holzgreve, W.; Lapillonne, A.; Putet, G.; Secher, N. J.; Symonds, M.; Szajewska, H.; Willatts, P.; Uauy, R. The roles of longchain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J. Perinat. Med. 2008, 36, 5−14. (3) Smithers, L. G.; Gibson, R. A.; Makrides, M. Maternal supplementation with docosahexaenoic acid during pregnancy does not affect early visual development in the infant: a randomized controlled trial. Am. J. Clin. Nutr. 2011, 93, 1293−1299. (4) Brémond-Gignac, D.; Copin, H.; Lapillonne, A.; Milazzo, S. Visual development in infants: physiological and pathological mechanisms. Curr. Opin. Ophthalmol. 2011, 22 (Suppl.), S1−S8. (5) Dutta-Roy, A. K. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. Am. J. Clin. Nutr. 2000, 71, 315s−322s. (6) Krauss-Etschmann, S.; Shadid, R.; Campoy, C.; Hoster, E.; Demmelmair, H.; Jiménez, M.; Gil, A.; Rivero, M.; Veszprémi, B.; Decsi, T.; Koletzko, B. V. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am. J. Clin. Nutr. 2007, 85, 1392−1400. (7) Harris, W. S.; Connor, W. E.; Lindsey, S. Will dietary omega-3 fatty acids change the composition of human milk? Am. J. Clin. Nutr. 1984, 40, 780−785. (8) Helland, I. B.; Smith, L.; Saarem, K.; Saugstad, O. D.; Drevon, C. A. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics 2003, 111, e39−e44. (9) Colombo, J.; Kannass, K. N.; Shaddy, D. J.; Kundurthi, S.; Maikranz, J. M.; Anderson, C. J.; Blaga, O. M.; Carlson, S. E. Maternal DHA and the development of attention in infancy and toddlerhood. Child Dev. 2004, 75, 1254−1267. (10) Hibbeln, J. R.; Davis, J. M.; Steer, C.; Emmett, P.; Rogers, I.; Williams, C.; Golding, J. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet 2007, 369, 578−585. (11) Zhang, J.; Wang, Y.; Meng, L.; Wang, C.; Zhao, W.; Chen, J.; Ghebremeskel, K.; Crawford, M. A. Maternal and neonatal plasma n-3 and n-6 fatty acids of pregnant women and neonates from three regions of China with contrasting dietary patterns. Asia Pac. J. Clin. Nutr. 2009, 18, 377−388. (12) Li, P.; Feng, X.; Liang, P.; Chan, H. M.; Yan, H.; Chen, L. Mercury in the seafood and human exposure in coastal area of Guangdong province, south China. Environ. Toxicol. Chem. 2013, 32, 541−547. (13) Grandjean, P.; Weihe, P.; White, R. F.; Debes, F.; Araki, S.; Yokoyama, Y.; Murata, K.; Sørensen, N.; Dahl, R.; Jørgensen, P. J. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol. Teratol. 1997, 19, 417−428. (14) Choi, A. L.; Grandjean, P. Methylmercury exposure and health effects in humans. Environ. Chem. 2008, 5, 112−120. (15) Oken, E.; Radesky, J. S.; Wright, R. O.; Bellinger, D. C.; Amarasiriwardena, C. J.; Kleinmann, K. P.; Hu, H.; Gillman, M. W. Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort. Am. J. Epidemiol. 2008, 167, 1171−1181.

AUTHOR INFORMATION

Corresponding Authors

*(X.S.) Tel: 86-10-87776914. E-mail: shangxh2002@aliyun. com. *(Y.W.) Tel: 86-10-67779118. E-mail: [email protected]. cn. Funding

This study was financially supported by the National Nature Science of Foundation of China (No. 81172675) and National Key Basic Research Program of China (No. 2012CB720804). Professor Jian Zhang from National Institute of Nutrition and Food Safety, China CDC, provided assistance in concentration analysis of fatty acids. Zhongjun Dun from Guangdong CDC provided assistance in probabilistic computation. Professor Shenglong Zhao from Zhejiang Ocean University provided 5212



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(16) Jensen, T. K.; Grandjean, P.; Jørgensen, E. B.; White, R. F.; Debes, F.; Weihe, P. Effects of breast feeding on neuropsychological development in a community with methylmercury exposure from seafood. J. Exposure Anal. Environ. Epidemiol. 2005, 15, 423−430. (17) Laird, B. D.; Goncharov, A. B.; Egeland, G. M.; Chan, H. M. Dietary advice on Inuit traditional food use needs to balance benefits and risks of mercury, selenium, and n3 fatty acids. J. Nutr. 2013, 143, 923−930. (18) FAO/WHO. Report of the joint FAO/WHO expert consultation on the risks and benefits of fish consumption; Food and Agriculture Organization of the United Nations: Rome; and World Health Organization: Geneva, 2011; 50 pp. (19) Du, Z. Y.; Zhang, J.; Wang, C.; Li, L.; Man, Q.; Lundebye, A. K.; Frøyland, L. Risk-benefit evaluation of fish from Chinese markets: nutrients and contaminants in 24 fish species from five big cities and related assessment for human health. Sci. Total Environ. 2012, 416, 187−199. (20) Mahaffey, K. R.; Sunderland, E. M.; Chan, H. M.; Choi, A. L.; Grandjean, P.; Mariën, K.; Oken, E.; Sakamoto, M.; Schoeny, R.; Weihe, P.; Yan, C. H.; Yasutake, A. Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption. Nutr. Rev. 2011, 69, 493−508. (21) Folch, J.; Lees, M.; Sloane Stanley, G. H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957, 226, 497−509. (22) Gao, Y. X.; Zhang, J.; Wang, C.; Li, L.; Man, Q.; Song, P.; Meng, L.; Lie, Ø.; Frøyland, L. The fatty acids composition of colostrum in three geographic regions of China. Asia Pac. J. Clin. Nutr. 2013, 22, 276−282. (23) Houserová, P.; Matejícek, D.; Kubán, V.; Pavlícková, J.; Komárek, J. Liquid chromatographic cold vapour atomic fluorescence spectrometric determination of mercury species. J. Sep. Sci. 2006, 29, 248−255. (24) Shang, X. H.; Li, X. W.; Zhang, L.; Zhao, Y. F.; Wu, Y. N. Estimation of methylmercury intake from the 2007 Chinese Total Diet Study. Food. Addit. Contam. B 2010, 3, 236−245. (25) Watzl, B.; Gelencser, E.; Hoekstra, J.; Kulling, S.; LydekingOlsen, E.; Rowland, I.; Schilter, B.; van Klaveren, J.; Chiodini, A. Application of the BRAFO-tiered approach for benefit-risk assessment to case studies on natural foods. Food Chem. Toxicol. 2012, 50, S699− S709. (26) Gao, Y. X.; Yue, B.; Yu, X.; He, J.; Shang, X.; Li, X.; Wu, Y. Fatty acid composition of edible marine fish in Zhoushan, Zhejiang Province. Zhonghua Yufang Yixue Zazhi 2013, 47, 552−555 (in Chinese). (27) He, J.-l. Analysis of methylmercury residue in seafish from Zhoushan area. Chin. J. Health Lab. Technol. 2013, 23, 971−972 (in Chinese). (28) Zeilmaker, M. J.; Hoekstra, J.; van Eijkeren, J. C.; de Jong, N.; Hart, A.; kennedy, M.; Owen, H.; Gunnlaugsdottir, H. Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment. Food Chem. Toxicol. 2013, 54, 30−34. (29) Cohen, J. T.; Bellinger, D. C.; Connor, W. E.; Kris-Etherton, P. M.; Lawrence, R. S.; Savitz, D. A.; Shaywitz, B. A.; Teutsch, S. M.; Gray, G. M. A quantitative risk−benefit analysis of changes in population fish consumption. Am. J. Prev. Med. 2005, 29, 325−334. (30) Guevel, M.; Sirot, V.; Volatier, J.; Leblanc, J. A risk-benefit analysis of French high consumption: a QALY approach. Risk Anal. 2008, 28, 37−48. (31) Ginsberg, G. L.; Toal, B. F. Quantitative approach for incorporating methylmercury risks and omega-3 fatty acid benefits in developing species-specific fish consumption advice. Environ. Health Perspect. 2009, 117, 267−275. (32) Loring, P. A.; Duffy, L. K.; Murray, M. S. A risk-benefit analysis of wild fish consumption for various species in Alaska reveals shortcomings in data and monitoring needs. Sci. Total Environ. 2010, 408, 4532−4541. (33) Tsuchiya, A.; Hardy, J.; Burbacher, T. M.; Faustman, E. M.; Mariën, K. Fish intake guidelines: incorporating n-3 fatty acid intake

and contaminant exposure in the Korean and Japanese communities. Am. J. Clin. Nutr. 2008, 87, 1867−1875. (34) Kaur, G.; Cameron-Smith, D.; Garg, M.; Sinclair, A. J. Docosapentaenoic acid (22:5n-3): a review of its biological effects. Prog. Lipid Res. 2011, 50, 28−34. (35) Sprecher, H.; Luthria, D. L.; Mohammed, B. S.; Baykousheva, S. P. Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J. Lipid Res. 1995, 36, 2471−2477. (36) Welch, A. A.; Shakya-Shrestha, S.; Lentjes, M. A. H.; Wareham, N. J.; Khaw, K. T. Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meateaters, vegetarians, and vegans and the precursor-product ratio of αlinolenic acid to long-chain n-3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort. Am. J. Clin. Nutr. 2010, 92, 1040− 1051. (37) Bakewell, L.; Burdge, G. C.; Calder, P. C. Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets. Br. J. Nutr. 2006, 96, 93−99. (38) Mozaffarian, D.; Rimm, E. B. Fish intake, contaminants, and human health evaluating the risks and the benefits. JAMA 2006, 296, 1885−1899. (39) Calder, P. C. n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am. J. Clin. Nutr. 2006, 83 (Suppl.), 1505S− 1519S. (40) Kogevinas, M. Human health effects of dioxins: cancer, reproductive and endocrine system effects. Hum. Reprod. Update 2001, 7, 331−339. (41) Lee, D. H.; Lee, I. K.; Song, K.; Steffes, M.; Toscano, W.; Baker, B. A.; Jacobs, D. R., Jr. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes results from the national health and examination survey 1999−2002. Diabetes Care 2006, 29, 1638−1644. (42) Jacobson, J. L.; Jacobson, S. W. Prenatal exposure to polychlorinated biphenyls and attention at school age. J. Pediatr. 2003, 143, 780−788. (43) Debes, F.; Budtz-Jørgensen, E.; Weihe, P.; White, R. F.; Grandjean, P. Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol. Teratol. 2006, 28, 536−547. (44) Davidson, P. W.; Myers, G. J.; Cox, C.; Axtell, C.; Shamlaye, C.; Sloane-Reeves, J.; Cernichiari, E.; Needham, L.; Choi, A.; Wang, Y.; Berlin, M.; Clarkson, T. W. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the Seychelles Child Development Study. JAMA 1998, 280, 701−707. (45) Myers, G. J.; Davidson, P. W.; Cox, C.; Shamlaye, C. F.; Palumbo, D.; Cernichiari, E.; Sloane-Reeves, J.; Wilding, G. E.; Kost, J.; Huang, L. S.; Clarkson, T. W. Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study. Lancet 2003, 361, 1686−1692. (46) Davidson, P. W.; Cory-Slechta, D. A.; Thurston, S. W.; Huang, L. S.; Shamlaye, C. F.; Gunzler, D.; Watson, G.; van Wijngaarden, E.; Zareba, G.; Klein, J. D.; Clarkson, T. W.; Strain, J. J.; Myers, G. J. Fish consumption and prenatal methylmercury exposure: cognitive and behavioral outcomes in the main cohort at 17 years from the Seychelles Child Development Study. Neurotoxicology 2011, 32, 711− 717.

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Risk and Benefit Assessment of Potential Neurodevelopmental Effect

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