Human health risk assessment for arsenic: A critical review

TL;DR: An up-to-date review of the different sources of arsenic, indicators of human exposure, epidemiological and toxicological studies on carcinogenic and noncarcinogenic health outcomes, and risk assessment approaches demonstrates a need for more work evaluating the risks of different arsenic species.

Abstract: Millions of people are exposed to arsenic resulting in a range of health implications. This paper provides an up-to-date review of the different sources of arsenic (water, soil, and food), indicators of human exposure (biomarker assessment of hair, nail, urine, and blood), epidemiological and toxicological studies on carcinogenic and noncarcinogenic health outcomes, and risk assessment approaches. The review demonstrates a need for more work evaluating the risks of different arsenic species such as, arsenate, arsenite monomethylarsonic acid, monomethylarsonous acid, dimethylarsinic acid, and dimethylarsinous acid as well as a need to better integrate the different exposure sources in risk assessments.

Summary

Introduction

• This paper provides an up-to-date review of the different sources of arsenic (water, 7 soil and food), indicators of human exposure (biomarker assessment of hair, nail, 8 urine and blood), epidemiological and toxicological studies on carcinogenic and non-9 carcinogenic health outcomes, and risk assessment approaches.
• Most studies evaluating 429 human exposure to arsenic have concentrated on total arsenic; relatively few have 430 looked at the role of individual arsenic species and this is a pressing research need.

Figures

Figure 1: a) Arsenic Sources - showing the release of arsenic from geological, anthropogenic and biological sources into ground water; b) Human exposure pathways through ingestion, inhalation and dermal contact; c) Mechanisms of arsenic mobilization into ground water hypothesized as arsenic adsorption by soil and its subsequent leaching into surface or ground water, arsenic release due to oxidation of pyrite or arsenopyrite, microbial and/or chemical reductive dissolution of iron oxyhydroxides, desorption and microbial mobilization, uncontrolled ground water abstraction and phosphate fertilizer; d) Arsenic enters the food chain from natural or anthropogenic sources and uptake by plants and crops from ground water used for irrigation.

Table 1: Inorganic and organic arsenic species

Table 5: Summary of human studies measuring biological arsenic in hair, nail and blood

Table 4: Summary of arsenic distribution in food items

Figure 2: Global distribution of arsenic in water indicated by GIS (Geographical Information System) characterisation of levels of arsenic in water sources of 43 countries. Lowest range up to WHO guideline of drinking water ≥10 µg l-1 indicated by green circle and highest level by red circle. See Table 2 for all references.

Table 8: Summary results of methodologies and tools adopted for risk assessment

Table 7: Summary of reported health effects of higher levels of arsenic

Table 3: Summary of arsenic distribution in soil

Table 2: Arsenic levels reported in ground or surface water by mobilization source

Table 6: Summary of human studies measuring biological arsenic in urine

Full text

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Rasheed, H orcid.org/0000-0003-2983-6867, Slack, R and Kay, P (2016) Human Health
Risk Assessment For Arsenic: A Critical Review. Critical Reviews in Environmental Science
and Technology, 46 (19-20). pp. 1529-1583. ISSN 1064-3389
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1
Human health risk assessment for arsenic: a critical review
1
Hifza Rasheed
1
, Rebecca Slack, Paul Kay 2
water@leeds, School of Geography, University of Leeds, United Kingdom 3
4
Abstract 5
Millions of people are exposed to arsenic resulting in a range of health implications. 6
This paper provides an up-to-date review of the different sources of arsenic (water, 7
soil and food), indicators of human exposure (biomarker assessment of hair, nail, 8
urine and blood), epidemiological and toxicological studies on carcinogenic and non-9
carcinogenic health outcomes, and risk assessment approaches. The review 10
demonstrates a need for more work evaluating the risks of different arsenic species 11
such as; arsenate, arsenite monomethylarsonic acid, monomethylarsonous acid, 12
dimethylarsinic acid and
dimethylarsinous acid as well as a need to better integrate 13
the different exposure sources in risk assessments. 14
15
Keywords: total arsenic, arsenic species, exposure pathways, biomarker 16
assessment, arsenic risk assessment, integrated risk assessment.
17
1
CONTACT Hifza Rasheed,
gyhj@leeds.ac.uk, water@leeds, School of Geography, University of Leeds, Leeds, LS2 9JT, United Kingdom.
Main Manuscript
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1. Introduction
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Arsenic is a toxic and carcinogenic chemical (International Agency for Research on 19
Cancer, 2012; Pellizzari and Clayton, 2006; Hughes, 2006) that is a naturally 20
occurring element and exists in the earth’s crust at an average concentration of 5 mg 21
kg
-1
(Garelick et al., 2008). It is not, however, homogenously distributed in the crust 22
and is more commonly associated with certain geological strata than others (Aronson, 23
1994; National Academy of Sciences, 1977). Whilst there are anthropogenic sources 24
of arsenic, geological weathering is the primary cause of arsenic release into 25
groundwater. This natural release of arsenic into ground or surface water poses a 26
global public health risk for approximately 140 million people in at least 70 countries 27
worldwide (Ravenscroft et al.,2009). Arsenic contaminated water also provides a 28
pathway for arsenic to enter the food chain via irrigation as well as during food 29
preparation and cooking (Bhattacharya et al.,2012; Fu et al.,2011; Mondal et al.,2010; 30
Zavala and Duxbury, 2008; Zhao et al.,2010; Rahman and Hasegawa, 2011; Halder et 31
al.,2014). Thus, ingestion of contaminated water and food is a significant exposure 32
pathway for arsenic. Long-term arsenic exposure has been associated with the 33
development of skin lesions, various types of cancer, developmental effects, 34
cardiovascular disease, neurotoxicity and diabetes (
Steinmaus et al., 2013; Martinez 35
et al., 2011). 36
Arsenic in water, food and soil exists in many different chemical forms and oxidation 37
states (International Agency for Research on Cancer, 2012) the most common 38
inorganic and organic arsenic compounds found in water, food, soil and biomarkers 39
referred to in this article are listed in Table 1. 40
Most of the trivalent and pentavalent arsenic species are absorbed in the body and 41
transported via the blood stream to the body tissues (Capitani, 2011). Metabolism is 42
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mainly dependent on reduction-oxidation reactions causing inter-conversion of
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trivalent and pentavalent arsenic species and methylation of As
+3
to yield methylated 44
arsenic species. Generally, inorganic arsenic forms are reported by Pal (2015) to be 45
more toxic than organo-arsenicals. As
+3
is considered comparatively more toxic than 46
As
+5
,
possibly due to interference of As
+3
on enzymatic processes by bonding to 47
sulfhydryl (–SH) or hydroxyl (–OH) functional groups (Kligerman et al., 2003; Mass et 48
al.,2001; Hughes, 2002). Past studies have shown that trivalent methylated arsenicals 49
are acutely more toxic and genotoxic than that of inorganic pentavalent arsenicals but 50
the relative toxicity of individual arsenic species, such as MMA
+3
or DMA
+3
is still 51
unknown (Tchounwou et al., 2003; Styblo et al., 2000; Viraraghaven et al., 1999). It 52
has been suggested that the methylation of inorganic arsenic reduces toxicity but data 53
are conflicting (Petrick et al., 2000; Petrick et al., 2001). Therefore, there are still 54
uncertainties regarding the potential risks and relative toxicity of individual arsenic 55
species in the human body. This critical review evaluates the current state of 56
knowledge on the distribution and potential risks of different arsenic species from 57
multiple exposure sources, through intake and uptake by the human body. It provides 58
an overview of the associated health risks from environmental exposures, which can 59
be used to eventually improve human health risk assessments. 60
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2. Methodology: Literature search and selection strategy 62
A number of scientific publications databases: (Medline;PubMed), Environmental 63
Sciences & Pollution Management (ESPM), the National Center for Biotechnology 64
Information (NCBI) and University of Leeds Library Pro-quest were interrogated to 65
identify peer-reviewed papers describing arsenic sources, exposure and risk, 66
published between January 1961 and June 2015. An additional search was conducted 67
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on secondary literature such as books, reports and conference proceedings published
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around the world. Studies were selected based on the following selection criteria: 69
a. Concentrations reported for arsenic in surface and ground water, food items, soil, 70
hair, nail, blood or urine. 71
b. Peer reviewed studies with methodological approach. 72
c. Potential health risks identified and associated to reported levels. 73
d. Risk estimates documented with variability and uncertainty. 74
e. Papers in English. 75
Of about 2000 items reviewed, 305 peer reviewed and published articles meeting the 76
above criteria have been included in this review. In addition to the review, the 77
relationships between total arsenic levels in water, soil, food and biomarkers identified 78
in different studies reported across 22 countries (Tables 2-6) were evaluated using 79
Pearson partial correlation analysis (SPSS 17.0, IBM, New York, NY, USA). Arsenic 80
risk assessment techniques used for carcinogenic or non-carcinogenic risks estimates 81
were also reviewed (Table 8) and critiqued to provide an overview of the current state 82
of knowledge, knowledge gaps and further research needs. 83
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3. Arsenic origin and mobilization 85
Arsenic is categorized into three main exposure sources based on its origin and 86
mobilization i.e. geological, anthropogenic and biological (Figure 1). Arsenic occurs in 87
combination with arsenopyrite or sulphide in more than 150 minerals (Budavari et al., 88
2001; Onishi and Sandell, 1955; Carapella, 1992). In addition to naturally occurring 89
arsenic deposits and sediments, other geological sources such as geothermal springs 90
and volcanic ash are common (Bhattacharya et al., 2006; Bundschuh et al., 2004; 91
Nordstrom, 2002). Anthropogenic sources include metal mining and smelting which 92
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