Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Expo Health. 2020 Apr 8;12(4):561–567. doi: 10.1007/s12403-020-00356-7

Arsenic exposure in relation to apple consumption among infants in the New Hampshire Birth Cohort Study.

AJ Signes-Pastor 1,2,*, T Punshon 1,3, KL Cottingham 1,3, BP Jackson 1,3, V Sayarath 1,2, D Gilbert-Diamond 1,2, S Korrick 4,5, MR Karagas 1,2
PMCID: PMC7665059  NIHMSID: NIHMS1591840  PMID: 33195875

Abstract

Infants and young children commonly consume apple-based products, which may contain high concentrations of inorganic arsenic (iAs). As yet, iAs exposure from ingesting apple products has not been well-characterized in early childhood. Therefore, we investigated the association between urinary arsenic concentrations and intake of apple products in one-year-old infants participating in the New Hampshire Birth Cohort Study. A three-day food diary prior to collection of a spot urine sample was used to determine infant’s consumption of apple products. The sum of urinary iAs, monomethylarsonic acid, and dimethylarsinic acid, referred to as ΣAs, was used to estimate iAs exposure. A total of 242 infants had urinary arsenic speciation analyzed without indication of fish/seafood consumption (urinary arsenobetaine < 1 μg/L) and with a completed three-day food diary. Of these, 183 (76%) infants ate apples or products containing apple. The geometric mean urinary ΣAs among the 59 infants who did not consume any type of apple product was 2.78 μg/L as compared to 2.38, 2.46, 2.28, and 2.73 μg/L among infants who exclusively consumed apple juice (n = 30), apple puree (n = 67), apples as whole fruit (n = 20) or products mixed with apples (n = 21), respectively. Differences in urinary ΣAs associated with apple consumption were not statistically significant in generalized linear models adjusted for urine dilution, rice consumption, and household water arsenic. Thus, while infants in our study frequently consumed apples and apple products, we did not find evidence that it increased iAs exposure.

Introduction

Arsenic is a ubiquitous element from both natural and anthropogenic sources present in various chemical forms (IARC, 2012). Inorganic arsenic (iAs), which has known human toxicity, and is regulated in public drinking water systems, has been detected in apple juice in the United States (USA) (Carrington et al., 2013; FDA, 2013; IARC, 2012; US EPA, 2001; Wilson et al., 2012). Elevated concentrations of arsenic in apple juice have been mainly attributed to the historical application of iAs pesticides to apple orchards (Renshaw et al., 2006; Schooley et al., 2008). In addition, juices reconstituted from concentrate could be contaminated from iAs-containing water (EFSA, 2009). The US Food and Drug Administration (FDA) proposed an action level for apple juice of 10 μg/kg that mirrors the current US EPA maximum contaminant level for drinking water (FDA, 2013; US EPA, 2001). While this action level is considered achievable with the use of good manufacturing practices, it is not yet legally enforceable (FDA, 2013). Other components of diet, including rice and rice-based products, can also be a source of iAs exposure (Carbonell-Barrachina et al., 2009; Cubadda et al., 2017; Signes-Pastor et al., 2016). For example, an action level of 100 μg/kg of iAs in infant rice cereals has also been proposed (FDA, 2016) paralleling the maximum level established in the EU (EC, 2015). Among populations with access to water with relatively low concentrations of arsenic (< 10 μg/L), diet is considered the primary source of exposure (EFSA, 2009; Nachman et al., 2018).

Infants and young children are the largest consumers of juice, per body weight, and apple juice is among the most popular juices in the USA (Consumer Reports, 2013; Tvermoes et al., 2014). Apples account for almost 20% of the total fruit intake of children and adolescents ages 2 to 19 years based on the NHANES (Herrick et al., 2015). However, apple consumption among younger ages < 2 years has not been well characterized nor is whether consumption is related to arsenic concentrations in biomarkers, such as urine among infants. Exposure to iAs, even at relatively low levels, is of particular concern during the vulnerable window of infancy and early childhood. Indeed, it may adversely affect long-term growth, neurodevelopment and respiratory health (Farzan et al., 2016; Gilbert-Diamond et al., 2016; Sanchez et al., 2016; Signes-Pastor et al., 2019b, 2019a; Vahter, 2008; Wasserman et al., 2014). Given this concern, we investigated the association between urinary arsenic concentrations and consumption of apples and apple products among infants in a cohort in the USA. We hypothesized that arsenic biomarker concentrations would be higher among infants consuming products consisting primarily of apples, e.g., whole fruit, apple juice, and pureed apple than among infants not consuming these products.

Material and methods

Study participants.

Our study comprised infants enrolled in the New Hampshire Birth Cohort Study (NHBCS), a longitudinal pregnancy cohort designed to examine the impacts of toxicants in drinking water and food on maternal-child health. Since 2009, the NHBCS has recruited pregnant women 18–45 years of age at approximately 24–28 weeks of gestation from prenatal clinics in the state of New Hampshire. Eligibility criteria included English literacy, the use of a private, unregulated water system at home (e.g., private well), not planning to move during pregnancy and a singleton birth (Gilbert-Diamond et al., 2011; Karagas et al., 2016). The Committee for the Protection of Human Subjects at Dartmouth College approved this study, and all participants provided written informed consent.

Food diary and urine sample collection

For our analysis, we selected infants who had reached one year of age during 2013 and 2016. Infants’ parents or caregivers were asked to complete a three-day food diary prior to a spot urine sample collection. The food diary included all foods and beverages consumed during three consecutive days. At the conclusion of the food diary, infants’ urine samples were collected with diapers and cotton pads. Samples were processed and frozen at −80°C within 24 hours until analysis for arsenic speciation as described previously (Karagas et al., 2016). A household tap water sample was also collected at enrollment and analyzed for arsenic content (Gilbert-Diamond et al., 2011).

Laboratory analysis

Urine specific gravity was analyzed using a handheld refractometer with automatic temperature compensation (PAL-10S; ATAGO Co Ltd). An Agilent LC 1260 equipped with a Hamilton PRP-100X column interfaced with an Agilent 8900 ICP-MS in collision cell mode was used to measure concentrations of urinary arsenic species, i.e., iAs (arsenite and arsenate), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), at the Trace Element Analysis Core at Dartmouth College. The arsenic species limit of detection (LOD) ranged from 0.06 to 0.10 μg/L across batches (Table S1). Total arsenic in tap water samples was measured with the Agilent 8900 ICP-MS in direct solution acquisition mode with a LOD of 0.04 μg/L.

Statistical analyses

The sum of urinary iAs, MMA, and DMA excluding AsB (ΣAs) was used as an estimate of iAs exposure. In our analysis, we excluded infants whose urinary AsB concentrations were ≥ 1 μg/L to reduce the likelihood of exposure misclassification by fish and seafood consumption (Navas-Acien et al., 2009). Urinary ΣAs was right-skewed, therefore, we applied a log10 transformation for further statistical analysis (log10 ΣAs).

Information recorded in the three-day food diary was used to classify infants who: i) did not eat any foods containing apples; consumed either ii) apple juice, iii) apple puree, or iv) or apple fruit and v) consumed products mixed with apples (i.e., apple snacks, apple yogurt, etc.). Each recorded entry of apple juice, apple puree and whole apple on the three-day food diary was considered an apple serving, and the sum of these responses the total number of servings of products with apple as the main ingredient.

We used general linear models (GLM) to assess the association between apple products and log10 ΣAs. We assessed whether there were differences in log10 ΣAs among infants who exclusively consumed either apple juice, apple puree, whole apple, or products mixed with apples with infants who did not consume any apple products as the reference category. We then evaluated the association between total number of servings of products with apple as the main ingredient and log10 ΣAs. We repeated this analysis for each type of apple-based product (i.e., exclusive consumption of apple juice, apple puree or whole apple). All GLMs were adjusted for urinary dilution (specific gravity), rice consumption (classified as no rice, foods containing mainly rice, and foods mixed with rice as described previously (Karagas et al., 2016)) and home tap water arsenic. In addition, we carried out a sensitivity analysis by adding infants’ sex (male/female), maternal smoking during pregnancy (yes/no) and maternal educational attainment (less than 11th grade or high school equivalent, junior college or some college, college graduate, postgraduate education) as potential confounding factors. All statistical analyses were conducted in R version 3.6.0, and the threshold of α = 0.05 was used to define associations as statistically significant.

Results and discussion

A total of 397 infants completed the three-day food diary (“original sample”) and urinary arsenic speciation was determined for 272 of these. Excluding 30 infants with AsB ≥ 1 μg/L (“excluded sample”) left 242 (89%) infants in the “final sample”. The original, final, and excluded samples had similar baseline characteristics (Table S2). Our final study sample was evenly distributed among female (n = 118) and male (n = 124) infants, and most of them (94%) had home tap water < 10 μg/L (Table 1).

Table 1:

Selected characteristics of study mothers and infants from the NHBCS for which both a three-day food diary and an infant spot urine sample were available at one year of age without indication of fish/seafood consumption overall, and stratified by the median of urinary ΣAs, and by apple consumption.

Selected characteristics Final sample No. (%) of infants
(n = 242)1 Urinary ΣAs Apple consumption
< 2.27 μg/L ≥ 2.27 μg/L No apple6 Mainly apple7
(n = 121) (n = 121) (n = 59) (n = 162)
Maternal age at enrollment, years
<25 16 (7) 11 (9) 5 (4) 3 (5) 11 (7)
25 – < 30 68 (28) 32 (26) 36 (30) 19 (32) 41 (25)
30 – 35 99 (41) 45 (37) 54 (45) 22 (37) 70 (43)
>35 59 (24) 33 (27) 26 (21) 15 (25) 40 (25)
Maternal education2
Less 11th grade or high school graduate or equivalent 19 (8) 15 (13) 4 (3) 5 (8) 13 (8)
Junior college or some college 47 (20) 24 (20) 23 (19) 9 (15) 33 (21)
College graduate 92 (39) 42 (35) 50 (42) 24 (41) 61 (39)
Postgraduate education 80 (34) 38 (32) 42 (35) 21 (36) 51 (32)
Mother smoked during pregnancy3
Yes 11 (5) 6 (5) 5 (4) 2 (3) 8 (5)
No 230 (95) 114 (95) 116 (96) 57 (97) 153 (95)
Infant sex
Male 124 (51) 59 (49) 65 (54) 27 (46) 89 (55)
Female 118 (49) 62 (51) 56 (46) 32 (54) 73 (45)
Tap water arsenic, μg/L
<1 168 (69) 90 (74) 77 (64) 44 (75) 110 (68)
1–10 60 (25) 24 (20) 31 (26) 13 (22) 37 (23)
>10 14 (6) 7 (6) 13 (11) 2 (3) 15 (9)
Gestational age, weeks – mean (IQR) 39.1 (1.6) 39.0 (1.6) 39.1 (1.6) 39.4 (1.7) 39.0 (1.7)
Urine specific gravity4 – mean (IQR) 1.01 (0.01) 1.01 (0.01) 1.01 (0.01) 1.01 (0.01) 1.01 (0.01)
Summed speciated urinary arsenic (Σ [iAs + MMA + DMA]), μg/L – geometric mean (sd5) 2.59 (0.42) 1.21 (0.22) 5.57 (0.27) 2.78 (0.44) 2.52 (0.4)
Open in a new tab
1

Infants without urinary arsenic concentrations measured (n = 125) and with urinary AsB concentrations ≥ 1 μg/L (n = 30) were excluded.

2

The maternal level of education was missing in 4 participants.

3

Information regarding maternal smoking during pregnancy was missing in 1 participant.

4

The urine specific gravity was missing in 1 participant, and thus, the mean specific gravity value was imputed in the statistical analyses.

5

sd refers to the standard deviation calculated using infants’ urinary log10 ΣAs.

6

Infants who did not consume any type of apple product.

7

Infants who consumed apple products in one or more of the three specific apple categories (i.e., apple juice, apple puree, or apple as whole fruit)

A total of 183 of the 242 (76%) reported consumption of any apple products, and 162 (67%) ate products with apple as the main ingredient (i.e., apple juice, apple puree, or apple as a whole fruit). Among infants consuming apples as juice, puree or whole fruit, the number of daily apple servings averaged 0.8 servings (ranging from 0.3 to 2.6) (Figure S1). The geometric mean urinary ΣAs, iAs, MMA, and DMA for the overall study group were 2.60 μg/L, 0.36 μg/L, 0.25 μg/L, and 1.80 μg/L, respectively (Table S1). No infant had concentrations below the detection limit for all species (i.e., iAs, MMA, and DMA).

Infants who consumed apple juice (n = 30), apple puree (n = 67), apple as whole fruit (n = 20), or foods mixed with apples (n = 21) exclusively had similar urinary ΣAs as those who did not consume apples with geometric mean urinary ΣAs values of 2.38 μg/L, 2.46 μg/L, 2.28 μg/L, 2.73 μg/L and 2.78 μg/L, respectively (Figure 1A). Similarly, the geometric mean ΣAs was 2.52 μg/L among those who consumed apple products in one or more of these three specific categories (n = 162) (Table 1). Urinary log10 ΣAs was unrelated to the total number of servings of apple products during the three consecutive days prior to urine collection (p-values > 0.05; Figure 1B, Figure 1C, Figure 1D, and Figure 1E). We did not detect major changes in our estimates in models adjusted for additional covariates performed as part of a sensitivity analysis (Table S3).

Figure 1:

Figure 1:

Open in a new tab

Urinary log10 ΣAs by apple consumption among infants from the NHBCS at one year of age. Each point represents one infant. In the boxplots, the central rectangle spans the first quartile to the third quartile (the interquartile range or IQR). The segment inside the rectangle shows the median. The “whiskers” on either side is 1.5*IQR. General linear models (GLM) were used to assess the association between apple consumption and urinary log10 ΣAs. The blue lines in Figure 1B, Figure 1C, Figure 1D, and Figure 1E depict the unadjusted linear models. The p-values refer to GLM models adjusted for urine dilution (specific gravity), rice consumption (categorized as no rice, foods containing mainly rice, and foods mixed with rice) and home tap water arsenic. Infants who did not eat any foods containing apples were used as the reference category in Figure 1A.

A.N = 197. No apple (n = 59), infants who did not consume any type of apple product; apple juice (n = 30), infants who consumed apple juice but not apple puree or apple fruit; apple puree (n = 67), infants who consumed apple puree but not apple juice or apple fruit; apple fruit (n = 20), infants who consumed apples but not apple juice or apple puree; and mixed with apple (n = 21), infants who consumed products mixed with apples and did not consume apple juice, apple puree or whole apple fruit. The geometric mean (standard deviation) infants’ urinary ΣAs concentration was 2.78 (0.44) μg/L, 2.38 (0.39) μg/L, 2.46 (0.43) μg/L, 2.28 (0.50) μg/L, and 2.73 (0.45) μg/L for non-consumers of apple products, and consumers of apple juice, apple puree, apple as whole fruit or foods mixed with apple, respectively.

B.N = 221. Bivariate association between the total number of servings of apple juice, apple puree and apples as a fruit consumed during the three days prior to urine sample collection and infants’ urinary log10 ΣAs, including those who did not consume apple products.

C.N = 89. Bivariate association between total number of serving of apple juice consumed during three days prior to urine sample collection and infants’ urinary log10 ΣAs, including those who did not consume apple products.

D.N = 126. Bivariate association between total number of servings of apple puree consumed during three days prior to urine sample collection and infants’ urinary log10 ΣAs, including those who did not consume apple products.

E.N = 79. Bivariate association between total number of servings of apple as a fruit consumed during three days prior to urine sample collection and infants urinary log10 ΣAs, including those who did not consume apple products.

In the USA, inorganic pesticides such as lead arsenate (PbHAsO4) were extensively applied to commercial apple orchards starting in the late 1800s and as a result left behind contaminated soil (Newton et al., 2006; Schooley et al., 2008). Edible vegetables and fruits grown in such soil may accumulate arsenic (Carbonell-Barrachina et al., 2009), especially in regions lacking strict pesticide regulations (Consumer Reports, 2013). In 2011, concerns were raised about both organic and inorganic arsenic concentrations in apple juice. In a total of 160 apple juice samples from 2005 to 2011, total arsenic concentrations ranged from 1 to 45 μg/kg, with 12% of samples with levels above 10 μg/kg (FDA, 2011a). Concentrations in a later batch of 94 apple juice samples from 2011 were all below the action level of 10 μg/kg of iAs (FDA, 2013, 2011b). Consumer Reports tested apple juices sold in the USA in 2018 and found that only one out of 22 apple juice products (5%) had an average iAs concentration above 10 μg/kg (Hirsch, 2019). The USA produces only about one sixth of its apple juice supply, so the majority of it is imported (Tvermoes et al., 2014). Surveillance of imported apple juice has uncovered high levels of iAs; Import Alert 20–05 – Detention Without Physical Examination and Surveillance of Fruit and Juices and Fruit Juices Due to Heavy Metal Contamination (FDA, 2019). Therefore, the potential for arsenic exposure from apples and apples products is not limited to produce grown in the USA.

The absence of any clear association between apple or apple product consumption and urinary arsenic concentrations among infants studied 2013 to 2016 in our cohort may reflect recent trends of diminishing iAs concentrations in products such as apple juice. However, other explanations for our results are possible. Our study population resided in northern New England and used private, unregulated water systems; therefore, it is conceivable that our findings were confounded by water arsenic concentrations, including by iAs in water used to reconstitute apple juice. For this reason, we adjusted all our models for household water arsenic concentrations. Another potential confounder was fish or seafood products consumption. To minimize this possibility, we excluded infants with urinary AsB concentrations ≥ 1 μg/L and used the sum of the iAs metabolites (i.e., iAs, MMA, and DMA) without AsB as our biomarker of iAs exposure. Further, in order to address the potential for residual confounding we performed sensitivity analysis including additional covariates. Residual confounding by other foods is also a possibility. While we adjusted for consumption of rice, a known source of arsenic exposure, there may have been other unknown dietary sources that confounded our results. We relied on self-reported diet, which tends to produce an accurate representation of actual diet (Willett, 2001), although non-differential misclassification cannot be excluded completely. The lack of any positive association between apple consumption and urinary arsenic concentrations also could have been due to insufficient statistical power but this is unlikely given our sample size. Finally, infants in our study may not be representative of populations elsewhere, but they do represent the experience of a relatively recent cohort.

Conclusions

The majority of infants in our study from the USA consumed apples or apple products. However, despite reports of elevated arsenic in apple juice, we did not detect elevated urinary concentrations of arsenic associated with ingestion of apple juice, apple puree, whole apples or products mixed with apples. Nonetheless, continued efforts are warranted to monitor and reduce arsenic exposure during the vulnerable developmental window of infancy and early childhood.

Supplementary Material

Supplemental information

Acknowledgements

This work was funded in part by grants from the National Institutes of Health: P01ES022832, R25CA134286, and P42ES007373, and the US EPA: RD83544201.

References

  1. Carbonell-Barrachina AA, Signes-Pastor AJ, Vázquez-Araújo L, Burló F, Sengupta B, 2009. Presence of arsenic in agricultural products from arsenic-endemic areas and strategies to reduce arsenic intake in rural villages. Mol Nutr Food Res 53, 531–541. 10.1002/mnfr.200900038 [DOI] [PubMed] [Google Scholar]
  2. Carrington CD, Murray C, Tao S, 2013. A Quantitative Assessment of Inorganic Arsenic in Apple Juice. URL https://www.fda.gov/media/86075/download [Google Scholar]
  3. Reports Consumer, 2013. Arsenic in Your Juice. Consumer Reports. URL https://www.consumerreports.org/arsenic-in-food/arsenic-in-your-juice-apple-juice-grape-juice/. [Google Scholar]
  4. Cubadda F, Jackson BP, Cottingham KL, Van Horne YO, Kurzius-Spencer M, 2017. Human exposure to dietary inorganic arsenic and other arsenic species: State of knowledge, gaps and uncertainties. Sci. Total Environ 579, 1228–1239. 10.1016/j.scitotenv.2016.11.108 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. EC, 2015. COMMISSION REGULATION (EU) 2015/ 1006 - of 25 June 2015 - amending Regulation (EC) No 1881/ 2006 as regards maximum levels of inorganic arsenic in foodstuffs 3. [Google Scholar]
  6. EFSA, 2009. Scientific Opinion on Arsenic in Food. EFSA Journal 7, 1351 10.2903/j.efsa.2009.1351 [DOI] [Google Scholar]
  7. Farzan SF, Li Z, Korrick SA, Spiegelman D, Enelow R, Nadeau K, Baker E, Karagas MR, 2016. Infant Infections and Respiratory Symptoms in Relation to in Utero Arsenic Exposure in a U.S. Cohort. Environ. Health Perspect 124, 840–847. 10.1289/ehp.1409282 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FDA, 2019. Import Alert 20–05. URL https://www.accessdata.fda.gov/cms_ia/importalert_56.html. [Google Scholar]
  9. FDA, 2016. FDA proposes limit for inorganic arsenic in infant rice cereal. FDA. URL http://www.fda.gov/news-events/press-announcements/fda-proposes-limit-inorganic-arsenic-infant-rice-cereal. [Google Scholar]
  10. FDA, 2013. Draft Guidance for Industry: Action Level for Arsenic in Apple Juice. U.S. Food and Drug Administration. URL http://www.fda.gov/regulatory-information/search-fda-guidance-documents/draft-guidance-industry-action-level-arsenic-apple-juice. [Google Scholar]
  11. FDA, 2011a. Arsenic in Apple Juice Analytical Results from the 2005–2011 Toxic Elements Food and Foodware Program. FDA. URL http://www.fda.gov/food/metals/arsenic-apple-juice-analytical-results-2005-2011-toxic-elements-food-and-foodware-program. [Google Scholar]
  12. FDA, 2011b. Results of Arsenic Analysis in Single-Strength Apple Juice, 2011 (ORA Sampling Assignment 2011102701). U.S. Food and Drug Administration. URL http://www.fda.gov/food/metals/results-arsenic-analysis-single-strength-apple-juice-2011-ora-sampling-assignment-2011102701 [Google Scholar]
  13. Gilbert-Diamond D, Cottingham KL, Gruber JF, Punshon T, Sayarath V, Gandolfi AJ, Baker ER, Jackson BP, Folt CL, Karagas MR, 2011. Rice consumption contributes to arsenic exposure in US women. PNAS 108, 20656–20660. 10.1073/pnas.1109127108 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR, 2016. Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire. Environ. Health Perspect 124, 1299–1307. 10.1289/ehp.1510065 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Herrick KA, Rossen LM, Nielsen SJ, Branum AM, Ogden CL, 2015. Fruit Consumption by Youth in the United States. PEDIATRICS 136, 664–671. 10.1542/peds. 2015–1709 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hirsch J, 2019. Arsenic and Lead Are in Your Fruit Juice: What You Need to Know. Consumer Reports. URL https://www.consumerreports.org/food-safety/arsenic-and-lead-are-in-your-fruit-juice-what-you-need-to-know/. [Google Scholar]
  17. IARC, 2012. Arsenic, Metals, Fibres, and Dusts. Lyon, France. [PMC free article] [PubMed] [Google Scholar]
  18. Karagas MR, Punshon T, Sayarath V, Jackson BP, Folt CL, Cottingham KL, 2016. Association of Rice and Rice-Product Consumption With Arsenic Exposure Early in Life. JAMA Pediatr 170, 609–616. 10.1001/jamapediatrics.2016.0120 [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nachman KE, Punshon T, Rardin L, Signes-Pastor AJ, Murray CJ, Jackson BP, Guerinot ML, Burke TA, Chen CY, Ahsan H, Argos M, Cottingham KL, Cubadda F, Ginsberg GL, Goodale BC, Kurzius-Spencer M, Meharg AA, Miller MD, Nigra AE, Pendergrast CB, Raab A, Reimer K, Scheckel KG, Schwerdtle T, Taylor VF, Tokar EJ, Warczak TM, Karagas MR, 2018. Opportunities and Challenges for Dietary Arsenic Intervention. Environmental Health Perspectives 126, 084503 10.1289/EHP3997 [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E, 2009. Arsenic exposure and Prevalence of Type 2 Diabetes: Updated Findings from the National Health Nutrition and Examination Survey 2003–2006. Epidemiology 20, 816–e2. 10.1097/EDE.0b013e3181afef88 [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Newton K, Amarasiriwardena D, Xing B, 2006. Distribution of soil arsenic species, lead and arsenic bound to humic acid molar mass fractions in a contaminated apple orchard. Environmental Pollution 143, 197–205. 10.1016/j.envpol.2005.12.001 [DOI] [PubMed] [Google Scholar]
  22. Renshaw CE, Bostick BC, Feng X, Wong CK, Winston ES, Karimi R, Folt CL, Chen CY, 2006. Impact of land disturbance on the fate of arsenical pesticides. J. Environ. Qual 35, 61–67. 10.2134/jeq2005.0096 [DOI] [PubMed] [Google Scholar]
  23. Sanchez TR, Perzanowski M, Graziano JH, 2016. Inorganic arsenic and respiratory health, from early life exposure to sex-specific effects: A systematic review. Environ. Res 147, 537–555. 10.1016/j.envres.2016.02.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schooley T, Weaver M, Mullins D, Eick M, 2008. The History of Lead Arsenate Use in Apple Production: Comparison of its Impact in Virginia with Other States 10, 32. [Google Scholar]
  25. Signes-Pastor AJ, Carey M, Meharg AA, 2016. Inorganic arsenic in rice-based products for infants and young children. Food Chem 191, 128–134. 10.1016/j.foodchem.2014.11.078 [DOI] [PubMed] [Google Scholar]
  26. Signes-Pastor AJ, Doherty BT, Romano ME, Gleason KM, Gui J, Baker E, Karagas MR, 2019a. Prenatal exposure to metal mixture and sex-specific birth outcomes in the New Hampshire Birth Cohort Study. Environmental Epidemiology. 10.1097/EE9.0000000000000068 [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Signes-Pastor AJ, Vioque J, Navarrete-Muñoz EM, Carey M, García-Villarino M, Fernández-Somoano A, Tardón A, Santa-Marina L, Irizar A, Casas M, Guxens M, Llop S, Soler-Blasco R, García-de-la-Hera M, Karagas MR, Meharg AA, 2019b. Inorganic arsenic exposure and neuropsychological development of children of 4–5 years of age living in Spain. Environ. Res 174, 135–142. 10.1016/j.envres.2019.04.028 [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tvermoes BE, Banducci AM, Devlin KD, Kerger BD, Abramson MM, Bebenek IG, Monnot AD, 2014. Screening level health risk assessment of selected metals in apple juice sold in the United States. Food Chem. Toxicol 71, 42–50. 10.1016/j.fct.2014.05.015 [DOI] [PubMed] [Google Scholar]
  29. US EPA, 2001. Drinking Water Arsenic Rule History. US Environmental Protection Agency. URL https://www.epa.gov/dwreginfo/drinking-water-arsenic-rule-history (accessed 10.29.19). [Google Scholar]
  30. Vahter M, 2008. Health Effects of Early Life Exposure to Arsenic. Basic & Clinical Pharmacology & Toxicology 102, 204–211. 10.1111/j.1742-7843.2007.00168.x [DOI] [PubMed] [Google Scholar]
  31. Wasserman GA, Liu X, Loiacono NJ, Kline J, Factor-Litvak P, van Geen A, Mey JL, Levy D, Abramson R, Schwartz A, Graziano JH, 2014. A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren. Environ Health 13, 23 10.1186/1476-069X-13-23 [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Willett W, 2001. Commentary: Dietary diaries versus food frequency questionnaires—a case of undigestible data. Int J Epidemiol 30, 317–319. 10.1093/ije/30.2.317 [DOI] [PubMed] [Google Scholar]
  33. Wilson D, Hooper C, Shi X, 2012. Arsenic and lead in juice: apple, citrus, and apple-base. J Environ Health 75, 14–20; quiz 44. [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental information
NIHMS1591840-supplement-Supplemental_information.docx (1.1MB, docx)

RESOURCES