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Fertilizers as a Source of Melamine and Cyanuric Acid in Soils: A Nationwide Survey in China Hongkai Zhu, Yu Wang, Hongwen Sun, and Kurunthachalam Kannan Environ. Sci. Technol. Lett., Just Accepted Manuscript • DOI: 10.1021/acs.estlett.8b00711 • Publication Date (Web): 17 Jan 2019 Downloaded from http://pubs.acs.org on January 18, 2019

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Environmental Science & Technology Letters

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Fertilizers as a Source of Melamine and Cyanuric Acid in Soils: A Nationwide Survey in

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China

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Hongkai Zhu,† Yu Wang,† Hongwen Sun,§ and Kurunthachalam Kannan*,†,‡

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†Wadsworth

Center, New York State Department of Health, and Department of Environmental

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Health Sciences, School of Public Health, State University of New York at Albany, Empire State

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Plaza, P.O. Box 509, Albany, New York 12201-0509, United States

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§MOE

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Environmental Science and Engineering, Nankai University, Tianjin 300071, China

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‡Biochemistry

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Key Laboratory of Pollution Processes and Environmental Criteria, College of

Department, Faculty of Science and Experimental Biochemistry Unit, King Fahd

Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia

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*Corresponding author at: Wadsworth Center, Empire State Plaza, P.O. Box 509, Albany, NY

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12201-0509, United States

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Phone: +1 518 4740015; Fax: +1 518 473 2895; e-mail: [email protected]

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ACS Paragon Plus Environment


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Graphic Abstract

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■ ABSTRACT

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The use of melamine and cyanuric acid in agriculture, industry, and consumer products has led to

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their ubiquitous environmental distribution. Nevertheless, little is known about the contamination

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of soils by melamine and cyanuric acid. Contamination of soils with melamine can lead to plant

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uptake and food chain transfer of these chemicals. In this study, concentrations of melamine and

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its three derivatives (cyanuric acid, ammeline and ammelide) were determined in 98 surface soils

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and 16 fertilizers collected across China in 2017. Elevated concentrations of ∑Melamine (sum of

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melamine and its three derivatives) were found in soils at concentrations that ranged from 8.67 to

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2020 ng/g dry weight (dw), with an average value of 213 ng/g dw. Melamine accounted for 63%

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of the total concentrations in soils, which was followed by cyanuric acid (28%). Elevated

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concentrations of melamine and cyanuric acid were found in nitrogenous fertilizers such as

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nitrolime (n = 3; mean: 284 µg/g) and urea (n = 4; mean: 3160 µg/g), respectively. The measured

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concentrations in fertilizers were 3 to 4 orders of magnitude higher than those found in soils.

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Farmland soils (mean: 545 ng/g dw) contained significantly higher concentrations of ∑Melamine

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than those of urban and background (forest) soils (92.5 ng/g dw). Our findings suggest that

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fertilizers are an important source of melamine and cyanuric acid in farm soils. Spatial distribution

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of melamine and cyanuric acid in soils showed the highest concentrations in Eastern China, which

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corresponded well with population density, industrial and agricultural activities. An ecological

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hazard assessment was performed of melamine in soils through a hazard quotient (HQ) approach.

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The mean HQ value was 0.35, and 7 of 98 surface soils had values above 1. Further studies are

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needed to discern uptake of melamine and its derivatives by crops and the fate of these chemicals

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in agricultural ecosystems.

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■ INTRODUCTION

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Melamine received worldwide attention from the pet food contamination incident in North

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America in 2007, which was followed by an adulterated milk scandal in China in 2008.1 Due to its

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high nitrogen content (67% by mass), melamine was deliberately added to milk and feed

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ingredients to increase the protein content. This incident led to exposure to melamine of over

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294,000 children in China, with at least six deaths from kidney-related diseases and kidney failure.2

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The severity of this incidence prompted global surveillance of melamine in infant formula, milk,

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and other dairy products, with measured concentrations ranging from below the limit of detection

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to 3630 ng/g.3-5 Nevertheless, melamine was reported to occur ubiquitously in human urine at

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concentrations on the order of several tens to hundreds of ng/mL,6 even in recent years (range:
150 km away from the production facility.25 That previous study was

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focused only on melamine, although other derivatives such as cyanuric acid can be present in

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soils.26 Considering that melamine can be hydrolyzed to cyanuric acid by soil bacteria, it is prudent

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that these chemicals are measured simultaneously to enable complete understanding of

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environmental transformation and fate.27

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The specific objectives of this study were to: (1) determine the concentrations and profiles of

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melamine, cyanuric acid, ammeline and ammelide in Chinese surface soils and select nitrogenous

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fertilizers; (2) elucidate sources and factors that affect melamine and cyanuric acid concentrations

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in soil; (3) examine the spatial distribution of melamine in Chinese soils; and (4) assess ecological

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risks of melamine in soils.

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■ MATERIALS AND METHODS

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Sample Collection. A total of 98 surface soil samples were collected across China during April

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to August 2017. The samples were collected at a depth of 0–10 cm using a handheld corer that was

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cleaned (in water) before and after each sample. The sampling locations are shown in Figure S1,

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and a detailed description of the sampling sites is given in Table S1 (in the Supporting Information).

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It should be noted that the sampling sites were selected randomly, primarily based on accessibility,

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and may not represent the entire geographical area. The samples consisted of soils from 5

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background, 20 rural, 47 urban, and 26 farmland locations. The background locations were remote

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forests >10 km away from any residential area. All rural and urban soils were forest, grassland,

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and roadside soils. Farmland soils were from currently cultivated agricultural lands. Soils were 5



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collected from multiple spots within a given location and then mixed thoroughly to obtain a

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representative sample. Soil samples were stored in pre-cleaned polypropylene (PP) tubes and

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transported to the laboratory, where they were air dried, sieved (< 2.0 mm), transferred into new

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PP tubes and stored at -20 °C until analysis.

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Six types of commercial nitrogenous fertilizers (n = 16) were purchased from agricultural

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chemical stores, and that include six synthetic fertilizers, four ureas, three nitrolimes, and a single

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sample of an organic fertilizer, calcium ammonium nitrate, and ammonium sulfate. All of these

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fertilizers were popular brands, commonly used by farmers as a source of nitrogen in China.

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Sample Pretreatment and Instrumental Analyses. Two different solid-liquid extraction

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methods were applied for the analysis of soil and fertilizer as described elsewhere.16, 22 Briefly, 0.1

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g of soil was extracted with 5 mL of methanol by shaking in an orbital shaker (250 oscillations/min;

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Eberbach, Ann Arbor, MI) for 6 h, after fortification with 10 ng of internal standard (ISs) mixture

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(15N3,13C3-melamine, 13C3-ammeline, 13C3-ammelide, and 15N3,13C3- cyanuric acid). Fertilizer (0.1

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g) samples were extracted with 40 mL of 5% formic acid in water (v/v), by shaking for 6 h, after

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fortification with ISs. The mixture was then centrifuged for 10 min at 4000 g (Eppendorf

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Centrifuge 5804, Hamburg, Germany), and the supernatant was transferred into another PP tube.

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For soil samples, the extraction step was repeated twice with 5 mL of 5 % formic acid in methanol

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(v/v), followed by concentration and solvent-reconstitution with 500 μL of the HPLC mobile phase

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(see below). For fertilizers, following extraction, 0.5 mL of the supernatant was diluted to 5.0 mL

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with the HPLC mobile phase. The final solutions were filtered through nylon syringe filters (pore

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size 0.2 µm; Corning, NY) directly into a glass vial for analysis by high performance liquid

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chromatography-tandem mass spectrometry (HPLC-MS/MS).

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Identification and quantification of melamine, cyanuric acid, ammeline and ammelide were

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performed on a Shimadzu LC-30AD Series HPLC system interfaced with API 5500 triple-

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quadrupole (MS/MS) mass spectrometer. Analytes were separated using acetonitrile (A) and 5

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mM ammonium formate buffer (pH 4.0; B) as mobile phases, by passing them through a Luna®

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hydrophilic-lipophilic interaction liquid chromatography column (100 mm × 3.0 mm, 3.0 μm

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particle size; Phenomenex, Torrance, CA). Two acquisition modes were used, i.e., the negative

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mode was applied for cyanuric acid and ammelide detection (0–4.5 min) and the positive mode

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was applied for melamine and ammeline detection (4.5–18 min). Compound specific MS/MS

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parameters as well as typical chromatograms of the target analytes present in samples are shown

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in Table S1 and Figure S2, respectively.

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Quality Assurance (QA)/Quality Control (QC). The carryover of target analytes between

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samples was eliminated by rinsing the autosampler syringe with a mixture of acetonitrile-water

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(50:50, v/v). Procedural blanks were analyzed by passing water through the entire analytical

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procedure. Both solvent blanks (acetonitrile) and procedural blanks were injected after every 20

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samples and no target analytes were found in blanks (Figure S2D). Quantification of target analytes

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was achieved by a ten-point calibration curve, that ranged in concentrations from 0.05 to 200

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ng/mL, and the regression coefficient of the calibration curve was >0.99. Duplicate analysis of

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randomly selected samples (n = 10) showed a coefficient variation of < 20% for the concentrations

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of target compounds measured in samples. The recoveries of target compounds (spiked at 20 and

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200 ng each) fortified into soils were between 75% and 96%. The average recoveries of ISs spiked

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into all soil samples were 81% for

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ammelide, and 70% for

15N ,13C -melamine, 3 3

15N ,13C -cyanuric 3 3

68% for

13C-ammeline,

72% for

13C-

acid. Isotope dilution method was used in the

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quantification. Limits of quantitation (LOQs; signal-to-noise ratio of 10) were 0.12 ng/g for

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melamine, 0.20 ng/g for ammeline, 0.10 ng/g for ammelide, and 0.25 ng/g for cyanuric acid.

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■ RESULTS AND DISCUSSION

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Occurrence of Melamine and Its Derivatives in Soils and Fertilizers. Melamine and its

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derivatives were found ubiquitous in surface soils, with a detection frequency (df) of 100% for

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melamine, ammelide, and cyanuric acid and 85% for ammeline (Table 1). The total concentrations

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of ∑Melamine (sum of melamine and its three derivatives) ranged from 8.67 to 2020 ng/g dry

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weight (dw), with a mean value of 213 ng/g dw and a median value of 78.3 ng/g dw. Among the

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four compounds analyzed, melamine (mean: 176 ng/g dw) was the predominant, followed by

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cyanuric acid (25.4 ng/g dw), ammeline (7.47 ng/g dw), and ammelide (4.11 ng/g dw). In an earlier

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study that focused on melamine contamination in soils near manufacturing factories, this

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compound was rarely found in farm soils >150 km away from the point sources of contamination.25

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Nevertheless, ubiquitous occurrence of melamine and its derivatives in soils in our study suggests

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the existence of major sources that contribute to contamination.

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To elucidate the sources of these compounds in Chinese surface soil, we analyzed 16

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commercially available nitrogenous fertilizers. Nitrogenous fertilizers such as urea were suspected

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as the sources of melamine/cyanuric acid, due to their similarities in chemical structure. The

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measured concentrations of melamine and its derivatives in fertilizers are shown in Table S3.

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Melamine and its derivatives were found in all fertilizers, and their concentrations ranged from

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4.37 to 483 (mean: 66.8) μg/g for melamine, from 0.206 to 26.4 (mean: 4.03) μg/g for ammeline,

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from 0.188 to 35.2 (mean: 8.49) μg/g for ammelide, and from 11 to 5260 (mean: 994) μg/g for

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cyanuric acid (Table 1). Except for cyanuric acid, the measured concentrations were below the 8


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provisional limit of 0.4% for melamine, as issued by the Food Safety and Consumer Affairs Bureau,

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Ministry of Agricultural, Forestry and Fisheries of Japan.28 Among six types of fertilizers analyzed,

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relatively high concentrations of melamine and cyanuric acid were found in nitrolime (n=3; mean:

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284 µg/g) and urea (n = 4; mean: 3160 µg/g), respectively. China is the largest producer and

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consumer of nitrogenous fertilizers and approximately 41 million tons of nitrogenous fertilizers

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were used in 2016 in China.29 These results suggest that fertilizers are the main sources of

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melamine and its derivatives found in soils in China. In addition, it should be noted that melamine

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and its derivatives can be formed from the transformation triazine-based herbicides like

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cyromazine.30 Other sources of melamine and cyanuric acid in soils include application of poultry

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manure, wastewater and sludge.20, 26, 31, 32

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Profiles and Correlations. The contribution of each target compound to the sum concentration

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of all four derivatives (∑Melamine) in soils and fertilizers is shown in Figure 1. For soils,

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melamine accounted for 63% (range: 10–99%) of the total concentrations, followed by cyanuric

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acid (range: 0.5–79%; mean: 28%), ammeline (range: 0.005–30%; mean: 6.0%), and ammelide

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(range: 0.15–13%; mean: 3%). For fertilizers, the composition of melamine and its derivatives

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varied depending on the fertilizer type. Specifically, cyanuric acid accounted for 99% of the total

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concentrations in ureas, followed by synthetic (89%) and ammonium (74%) fertilizers. In contrast,

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melamine was the most abundant compound found in nitrolime (72%). Cyanuric acid can be

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formed by thermal degradation of urea. The measured concentrations of melamine and cyanuric

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acid are impurities of these compounds formed during the fertilizer production processes.

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In our earlier studies, we showed that melamine (59% of total) was the most abundant compound,

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followed by cyanuric acid (38%) in indoor dust samples.16 In contrast, cyanuric acid (68–82%)

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was the major compound found in infant formulas, dairy products, and human urine.8, 33 These 9



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results suggest a compositional shift from melamine to cyanuric acid from environmental (e.g. soil

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and dust) to biological samples (e.g. food, urine). Melamine was the dominant compound in

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environmental matrices, whereas cyanuric acid was the prevalent compound in biological samples.

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Biotransformation of melamine to cyanuric acid in soils and by microbial cultures has been

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reported earlier.27, 34, 35 Further studies are needed to understand the fate of melamine and cyanuric

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acid in the food chain, especially in agricultural ecosystems.

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A significant correlation (Spearman correlation; 0.406 < r < 0.578, p < 0.01) existed between

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the concentrations of melamine and ammeline/ammelide (Table S4), which indicated a common

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source of origin for these three compounds. These results are consistent with the fact that ammeline

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and ammelide are intermediates formed during environmental and biological transformation of

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melamine or are present as impurities in melamine-based products.36 A significant (Spearman

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correlation; p < 0.01), but weak correlation (r = 0.261), however, was found between melamine

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and cyanuric acid (Table S4), which suggested the existence of multiple sources for these two

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compounds. On the one hand, cyanuric acid can be formed from the hydrolysis of melamine. On

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the other hand, cyanuric acid by itself is used in a variety of applications. As a hydrolysate of

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chloroisocyanurates (e.g., sodium dichloroisocyanurate and potassium dichloroisocyanurate),

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cyanuric acid is used in dishwashing detergents, sanitizing solutions, and drinking water treatment

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products.37

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Geographical Distribution of Melamine and Its Derivatives in Surface Soils. The spatial

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distribution of ∑Melamine in Chinese surface soils was examined on the basis of land-use pattern,

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administrative divisions, latitude, and longitude (Figure 2). The sampling locations were classified

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into four land-use categories, i.e. farmland, urban, rural and background; six administrative

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divisions namely, East China (EC), Northeast China (NE), Southwest China (SW), Northwest 10


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China (NW), South Central China (SC), and North China (NC).38 Depending on the economic

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development and climate, latitude and longitude were divided into three subgroups, i.e., [< 30oN,

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30–38oN, >38oN] and [120oE].

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Soil samples collected from farmlands (mean: 545 ng/g dw) contained significantly higher

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∑Melamine concentrations than those from urban (114 ng/g dw), rural (61.1 ng/g dw), and

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background (16.4 ng/g dw) areas (Independent sample t-test; p < 0.001; Figure 2A). High

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concentrations in farm soils suggest exposure to melamine and cyanuric acid found in nitrogenous

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fertilizers. In comparison to rural soils, significantly higher ∑Melamine concentrations were found

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in urban soils (Independent sample t-test; p < 0.05), which suggests the existence of other potential

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sources in the urban environment. Melamine is used in products such as paints, dinnerware,

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plastics and flooring. Remarkable spatial variation was found in ∑Melamine concentrations among

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the six administrative divisions. Surface soil collected from EC contained the highest

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concentrations of ∑Melamine (mean: 320 ng/g dw), followed by those from NE (281 ng/g dw),

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SW (270 ng/g dw), NW (225 ng/g dw), SC (103 ng/g dw), and NC (84 ng/g dw) (Figure 2B). This

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spatial distribution pattern aligns with the application rates of nitrogenous fertilizers across

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China.39 The concentrations of ∑Melamine in soils were enriched in eastern part (> 120 oE; mean:

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381 ng/g dw) at low latitudes (< 30 oN; mean: 273 ng/g dw) (Figure 2C and D). This region is also

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known for its intensive industrial and e-waste recycling operations in China.40,

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geographical pattern of contamination was reported for brominated flame retardants, perchlorate,

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and per- and poly-ﬂuoroalkyl substances.38,

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production of melamine-formaldehyde resin which is used in the manufacture of plastics,

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kitchenware, and dishware.44 In addition, melamine and cyanuric acid are used as flame retardants

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in furnishings, intumescent paints, textiles, and electrical appliances.45

42, 43

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A similar

Melamine and its derivatives are used in the

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Hazard Assessment. Potential hazards of melamine contamination in soil were evaluated through a hazard quotient (HQ) approach, as shown in Eq (1): HQ = PECsoil/PNECsoil

(1)

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where PECsoil is the melamine concentration in soil (ng/g dw). PNECsoil is the predicted no-

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effect concentration (ng/g dw). A PNEC value of 500 ng/g soil was adapted from a study that

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measured growth of four plants, Hordeum vulgare, Tritium aestivum, Raphanus sativus, and

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Lepidum sativum in melamine contaminated soil.18 This value was derived from the LC50 value

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(median lethal concentration), which was then divided by a safety factor of 1000. However,

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PNECsoil values were not available for ammeline, ammelide and cyanuric acid and therefore HQs

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were not calculated for these three compounds. A HQ value of ≥ 1 indicates a potential risk; 0.1 ≤

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HQ ≤ 1 indicates a moderate to low risk; and 0.01 ≤ HQ ≤ 0.1 indicates minimal to negligible risk.

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Overall, the calculated HQ values in Chinese soils ranged from 0.0025 to 4.02 with mean value

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of 0.351. These HQ values were 1~2 orders of magnitude higher than those reported for soils from

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a melamine factory in China (3.5 × 10-4 to 1.1 × 10-2).18 The HQ values were < 0.1 for 47% of soil

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samples, which suggested a minimal/negligible risk from melamine contamination (Figure 3). A

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moderate to low risk was found for 46% of the soil samples analyzed (HQ: 0.1–1). The HQ values

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were above 1 for 7 of 98 surface soil samples, indicating a potential for risk from melamine

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contamination. Another study reported a soil PNEC value of 2500 ng/g for earthworm.46 The calculated HQ values

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based on earthworm reproduction were 0.0005–0.804 with a mean value of 0.070. It should be noted that there exists

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considerable uncertainty in PNEC values for soil melamine. Further studies are needed to assess the effects of cyanuric

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acid in combination with melamine in soil ecosystems.

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Previous studies have reported uptake of melamine by crop plants.25, 47, 48 Melamine was also

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found in farm animal tissues (e.g., pigs, ruminants, fish, and poultry) and products (e.g., eggs and

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milk).25, 49-53 Our study provides evidence that residual melamine and its derivatives present in 12


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nitrogenous fertilizers contribute to contamination of farm soils, which results in food chain

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transfer and human exposures. Environmental fate of melamine in agricultural ecosystems requires

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further studies.

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■ ASSOCIATED CONTENT

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Supporting Information

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Details of analytical materials/reagents, instrumental analysis, and data analysis. Tables

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containing multiple reaction monitoring (MRM) transitions of target chemicals (Table S1),

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information on soils and fertilizers as well as corresponding target chemical concentrations (Table

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S2 and S3) and correlation analysis (Table S4). Figures showing sampling locations (Figure S1)

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and typical chromatograms of target chemicals in soil and fertilizers (Figure S2). This information

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is available free of charge on the ACS Publications website.

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■ AUTHOR INFORMATION

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Corresponding Authors

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*Phone: +1 518 474 0015; fax: +1 518 473 2895; e-mail:

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[email protected].

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Notes

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The authors declare no competing financial interest.

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Table 1. Concentrations of melamine, cyanuric acid, ammeline and ammelide in surface soils (ng/g dw) and fertilizers (µg/g) collected from China

Soil (n=98; ng/g dw)

Fertilizer (n=16; µg/g)

Min-Max Mean Median df/% Min-Max Mean Median df/%

Melamine 1.23–2010 176 55.9 100 4.37–483 66.8 9.04 100

Ammeline nd–96.1 7.47 3.44 85 0.206–26.4 4.03 1.54 100

Ammelide 0.106–54.7 4.11 1.91 100 0.188–35.2 8.49 2.99 100

430 431

19


Cyanuric acid 3.68–211 25.4 17.0 100 11–5255 994 250 100

∑Melamine 8.67–2020 213 78.3 100 17.4–5600 1070 458 100


432 433

434 435 436 437

Figure 1. Composition proﬁles of melamine and its derivatives in surface soil and fertilizer samples collected from China. SF: synthetic fertilizer; Others: including organic fertilizer, calcium ammonium nitrate, and ammonium sulfate.

438 439

20


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440 441 442 443 444 445 446

Figure 2. Mean ∑melamine (sum of melamine and its three derivatives; error bars for 95% confidence intervals) concentrations stratified by land use pattern (A), administrative divisions (B), latitude (C), and longitude (D) of surface soil samples collected from mainland China. FL: farmland; UR: urban; RU: rural; BG: background. EC: East China; NE: Northeast China; SW: Southwest China; NW: Northwest China; SC: South Central China; NC: North China. *: p < 0.05; ***: p < 0.001.

21



447 448 449 450

Figure 3. Distribution of hazard quotients of melamine in surface soils collected from China. The HQ values displayed here were calculated from the reference value available for plants (500 ng/g soil) from the OECD report in 1998.

451 452

22


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A Nationwide Survey in China - ACS Publications - American

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