Case Report

Annals of Clinical Biochemistry

2015, Vol. 52(4) 510–515
! The Author(s) 2014
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DOI: 10.1177/0004563214559222
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Homicidal arsenic poisoning

Andrew Duncan1, Andrew Taylor2, Elizabeth Leese3, Sam Allen4, Jackie Morton3 and
Julie McAdam5

Abstract
The case of a 50-year-old man who died mysteriously after being admitted to hospital is reported. He had raised the
possibility of being poisoned prior to his death. A Coroner’s post-mortem did not reveal the cause of death but this was
subsequently established by post-mortem trace element analysis of liver, urine, blood and hair all of which revealed very
high arsenic concentrations.

Keywords
Toxicology, arsenic, homicide
Accepted: 4th October 2014

Introduction thought he may have been poisoned as he had felt

In the past, arsenic has been a popular choice of poison unwell following a meal.
used for suicide and homicide; however, more recently He returned to the UK via Pakistan where he again
its availability in UK and USA has been restricted. visited relatives. In Pakistan, he presented to a local
Only two cases of intentional arsenic poisoning have hospital with diarrhoea and vomiting. He was diag-
been reported in the western literature since 1992.1,2 nosed with Helicobacter pylori infection and was com-
We present a recent case of unexplained sudden menced on H. pylori eradication therapy. After
death. The case was reported to the Procurator Fiscal returning to the UK and around seven weeks after
(Scottish equivalent to the Coroner), and a diagnostic the onset of his illness, he presented to his GP with
forensic process was instigated that supported the con- diarrhoea, vomiting and a tender abdomen. The patient
clusion that the man died as a direct result of maleficent was referred to hospital.
arsenic poisoning.

1
Scottish Trace Element & Micronutrient Reference Laboratory, Glasgow
Case report Royal Infirmary, Glasgow, UK
2
A 50-year-old man of Pakistani origin who had been Department of Clinical Chemistry, Royal Surrey County Hospital,
Guildford, UK
living in Saudi Arabia with relatives for three months, 3
Health and Safety Laboratory, Buxton, UK
presented with a six-week history of diarrhoea and 4
University Hospital Crosshouse, Crosshouse, UK
vomiting. He also reported general malaise, abdominal 5
Forensic Medicine and Science, Glasgow University, Glasgow, UK
tenderness, mild fever, numbness in his arms and legs
Corresponding author:
and blurring of vision. He had lost approximately 15 kg Andrew Duncan, Scottish Trace Element & Micronutrient Reference
in weight. When his symptoms began, he had volun- Laboratory, Glasgow Royal Infirmary, Glasgow G4 0SF, UK.
teered to his partner, a nephew and a friend that he Email: [email protected]
Duncan et al. 511

There was no significant medical history, but the to the Procurator Fiscal (Scotland), and a post-mortem
patient had been shot in the leg, allegedly by a relative examination was instructed.
during a trip to Pakistan around a year before his At post-mortem, there were few pathological find-
death. ings. External examination revealed petechial haemor-
On general examination, he looked well. His tem- rhages in and around the eyes, in the mouth and over the
perature, pulse, blood pressure, respiratory rate and trunk and right upper arm and an area of darker brown
oxygen saturations were normal. He had moderate ten- discolouration of the skin over the back. Internally, there
derness over the right hypochondrium. were bilateral pleural effusions, the trachea contained a
Laboratory findings on admission showed pancyto- large amount of frothy fluid and there was non-specific
penia and deranged liver function tests (reference pulmonary congestion and oedema. The liver was con-
ranges in parentheses): haemoglobin 117 g/L (130– gested reflecting the deranged liver function tests, and
180 g/L), white blood cells 1.0  109/L (4–11  109/L); there was focal reddening of the lining of the ascending
platelets 95  109/L (150–400  109/L); mean cell colon, the remainder of the gastrointestinal tract being
volume 80 fL (78–99 fL); neutrophils 0.4  109/L normal. Microscopy revealed very occasional contrac-
(2–7.5  109/L); lymphocytes 0.4  109/L (1.5–4  109/ tion bands in the myocardium and some scattered
L); vitamin B12 1053 ng/L (200–900 ng/L); folate mixed inflammatory cells in the liver sinusoids, but no
4.3 mg/L (3.1–20 mg/L); ferritin 422 mg/L (10–275 mg/L); unequivocal hepatocyte necrosis. Several oval scars were
urea 10.3 mmol/L (2.5–7.8 mmol/L); creatinine present on the front of each thigh. The entire body was
122 mmol/L (40–130 mmol/L); total bilirubin 46 mmol/L X-rayed prior to post-mortem, and pieces of lead shot
(<20 mmol/L); alkaline phosphatase 70 U/L (30–130 U/ were subsequently retrieved from the right thigh and
L); aspartate aminotransferase 78 U/L (<40 U/L); ala- scrotum. No Geiger counter was used.
nine aminotransferase 103 U/L (<50 U/L); calcium Samples of liver, urine, blood and hair were collected
2.15 mmol/L (2.2–2.5 mmol/L); phosphate 1.83 mmol/ for routine toxicology and toxic trace element analysis.
L (0.8–1.5 mmol/L); C-reactive protein 16 mg/L Arsenic, lead, mercury and thallium were measured by
(<10 mg/L); lactate 1.5 mmol/L (0.5–2.2 mmol/L); and inductively-coupled plasma mass spectrometry (ICP-
amylase 98 U/L (<10 U/L). MS). Concentrations of lead, mercury and thallium
Tests for HIV-antigen/antibody, hepatitis Bs-anti- were within reference limits but arsenic was grossly ele-
gen, hepatitis C antibody, malaria blood film and anti- vated in all samples (Table 1): blood, 7.0 mmol/L (refer-
gen, anti-nuclear antibodies, mitochondrial antibody ence range <0.135 mmol/L); urine, 64.5 mmol/L
and smooth muscle antibody were all negative. A (reference range <0.25 mmol/L); liver, 39 mg/g; 3 mm sec-
blood film showed moderate anisocytosis with some tions of hair from root end, 71, 74, 44, 24, 14, 11, 10, and
polychromasia. There was marked leucopenia and 11 mg/g (reference range <0.5 mg/g). The latter showed a
thrombocytopenia. The chest X-ray was normal. gradual increase in arsenic exposure over time with high-
Abdominal ultrasound reported a trace of free fluid est concentrations in the month before his death.
within the pelvic cavity. An electrocardiography was Speciation of arsenic in urine was performed by
scheduled for the following morning; however, that micro flow liquid chromatography coupled to ICP-
morning the patient was found deceased hanging over MS3 (see Figure 1). The peak fraction which was
the side of his bed. The patient was already cold and unidentified was collected by high-performance liquid
resuscitation was not attempted. The case was referred chromatography and analysed by micro liquid

Table 1. Concentrations of arsenic species in a post-mortem urine sample.

Reference range Reference range

Arsenic concentration 95th percentile Arsenic concentration 95th percentile
Urinary arsenic species (mmol/L) (mmol/L) (mmol/mol creatinine) (mmol/mol creatinine)

Arsenic3þ 5.5 (8.5%) 0.007 983 <0.99

Arsenic5þ 2.4 (3.7%) 0.003 421 <0.35
Monomethyl arsenic 1.2 (1.9%) 0.03 219 <3.1
Dimethyl arsenic 17.5 (27.1%) 0.17 3122 <16.1
Arsenobetaine 0.07 (0.1%) 1.7 12 <175
Dimethylthio arsenic Approximately 38 (58.6%)a Not known Approximately 6750a Not known
The percentage of the total arsenic concentration is shown in parentheses.
a
Not quantified directly; derived from total arsenic measured minus the sum of the other quantified species.
512 Annals of Clinical Biochemistry 52(4)

chromatography-ICP-MS and electro-spray ionisation- 3–4 h after exposure.13 Even with relatively low arsenic
tandem mass spectrometry. The mass spectrum of this exposure, urine concentrations may be high in urine
peak showed a fragmentation pattern that was similar that has been collected soon after ingestion; for exam-
to the mass spectrum obtained from dimethylthioarse- ple, six healthy volunteers had urine arsenic concentra-
nic ((CH3)2As(S)O). The mass spectrum results are also tions of up to 37 mmol/L 10 h after a relatively small
consistent with a previous study of dimethylthioarsenic bolus dose of 6 mg arsenic trioxide.14
identification.4 The main factors affecting arsenic concentrations in
blood and urine are the time from poisoning to sample
collection and the amount of arsenic consumed.
Discussion Unfortunately, very few publications document the
This patient’s blood arsenic result of 7 mmol/L was sub- former and the latter is rarely known. Since the half-
stantially higher than our upper reference limit of life of arsenic in these samples is very short, concentra-
0.135 mmol/L but considerably lower than other fatal tions will decrease rapidly over a brief time period. For
cases of arsenic poisoning, for example 96 mmol/L5 in this reason, it is only possible to make limited infer-
one case, an average of 49 mmol/L (range: 4 to ences from blood and urine concentrations.
267 mmol/L) reported in a series of 19 victims6 and The incorporation of trace elements in hair, finger-
144 mmol/L (range: 8 to 1802 mmol/L) in a subsequent nails (not collected in this case) and liver is more likely
series of 18 victims.7 However, the time from poisoning to be in proportion to the systemic burden and so com-
to blood collection was not quoted in these studies and parison of arsenic concentrations in these tissues with
since the half-life of arsenic in vivo is around 48 h,8 blood reported fatal poisonings is likely to be a more reliable
concentrations fall quickly. Consequently, blood taken means of assessing degree of exposure.
on the day of poisoning shows much higher concentra- Measurement of trace elements in longitudinal sec-
tions than samples taken several days later as was the tions of hair has been used to gauge the approximate
case in the present report in which three days passed time course of exposure using the known growth rate of
between leaving Pakistan and his death. hair per month. Acute arsenic poisoning may be asso-
Urine arsenic concentrations fall quickly after a ciated with excessive sweating, and in such cases, con-
single arsenic exposure9,10 and so interpretation is dif- centrations of arsenic in hair may be due to
ficult. The victim had a post-mortem urine arsenic con- contamination of arsenic in sweat as well as incorpor-
centrations of 65.4 mmol/L compared to 49.9 mmol/L ation systemically so making interpretation more diffi-
found in another fatal case although in the current cult.15 However, in the current case, excessive sweating
case, the time from exposure was indeterminate and was not reported and so longitudinal hair analysis was
in the latter was not recorded. In two other severe but undertaken. A head hair arsenic concentration of 71 mg/
ultimately non-fatal cases, concentrations of 70.8 and g (reference values <0.15 mg/g16) was found in the 3-
77.4 mmol/L were found on the day of exposure.11 A mm head hair sample cut closest to the scalp. This is
concentration of 2777 mmol/L was found in one non- high and in keeping with previous reports of fatal
fatal case in which the sample was collected the day arsenic poisonings, for example 10, 94, 147 and
after poisoning12 and in a failed suicide attempt the 400 mg/g found in four cases17,18 and results from 28
urine concentration was found to be 734 mmol/L only to 226 mg/g and 7.4 to 37 mg/g in sections along the

Figure 1. Arsenic speciation chromatogram of post-mortem urine sample.

DMA: dimethylarsinous acid.
Duncan et al. 513

length of hair in two case reports.17,19 The victim’s hair but in an inhaled dust exposure more that 50% of the
was 25 mm long representing around the last 10 weeks total arsenic was methylated in the urine sample.25
of his life based on an average growth rate of approxi- In the present case, very high concentrations of both
mately 10.6 mm/month.20 Arsenic concentrations were monomethyl arsenic and dimethyl arsenic were
high along the length suggesting he had been poisoned detected indicating considerable detoxification of inor-
over this entire time period. This is in accord with the ganic arsenic by methylation had occurred. The
duration of his symptoms which started approximately unidentified peak was thought to be dimethylthioarse-
70 days before his death. Unfortunately, his hair was nic which has a high degree of cytotoxicity being pos-
not long enough to give an indication of when the sibly more toxic than arsenite.27 Although biological
exposure started. The arsenic concentrations increased pathways are not fully understood, current research
incrementally from the distal end along the 3 mm suggests dimethylthioarsenic is produced following
lengths of hair analysed, suggesting that the amount exposure to inorganic arsenic.28
of arsenic absorbed increased over time. This is also The victim had spent time in Pakistan where concen-
consistent with the chronic presentation of his trations of inorganic arsenic in water from bore wells
symptoms. are elevated compared to the UK.29,30 For example, in
The liver arsenic concentration in this case was a report of 330 Pakistani subjects, the median urine
39 mg/g (reference range: <0.013 mg/g21). Previous concentration was 1.6 mmol/L in exposed individuals
reports of fatal arsenic poisoning reported liver concen- but these ranged up to 28.9 mmol/L (2166 mg/L).31 In
trations of 15 mg/g,5 30 mg/g,22 226 mg/g,19 147 mg/g23 another study, urine concentrations as high as
and an average of 81.7 mg/g (range: 5 to 400 mg/g) in a 24.6 mmol/L were found.32 Although urine arsenic con-
series of 19 cases.7 centrations are usually lower than those found in fatal
The arsenic concentrations found in the blood, poisoning, on occasions this is not the case. However,
urine, liver and hair tissues collected are therefore in individuals imbibing arsenic in drinking water over
keeping with previously reported cases of fatal arsenic long time periods have chronic exposure resulting in
poisoning. Such concentrations could be achieved acci- skin pigmentation, keratosis and increased risk of
dentally through inadvertent exposure from food, skin cancer.33,34 In addition, an inconceivably high
water, medication or in the workplace. However, the volume of water would have to be drunk in order to
victim was a businessman and not occupationally accumulate an acute lethal dose estimated to be 100 to
exposed in processes, such as semiconductor manufac- 300 mg35; in the two studies mentioned above, the max-
ture, academic research, use of arsenic containing wood imum arsenic concentrations in water were 332 mg/L
preservative or other work in which arsenic is used, nor and 1840 mg/L. Rice grown and cooked in arsenic-
was he being treated with an arsenical medication.24 containing water has also been shown to have high
The concentration of arsenic is negligible in food- inorganic arsenic concentrations (up to 482 mg/g).36
stuffs with the exception of seafoods in which it may However, again this would result in chronic arsenic
be as high as 27 mg/g in the case of oysters and 40 mg/g poisoning and unrealistically large quantities of rice
in seabass. Consequently, following a fish or shellfish would require to be eaten to attain a lethal dose.
meal, high concentrations in excess of 13 mmol/L23 and The natural history of the case presented is in keep-
29 mmol/L25 (reference limit <0.25 mmol/L) have been ing with an acute arsenic poisoning which is associated
reported. The main food sources of arsenic are in the with symptoms of nausea, vomiting, diarrhoea and
form of non-toxic compounds; arsenobetaine and often abdominal pain, tachycardia and profound hypo-
arsenocholine in fish and shellfish and arsenosugars in tension.15 The victim also gave a history of weight loss
seaweed. Arsenobetaine is rapidly excreted unchanged and peripheral neurological symptoms which have also
in the urine,26 and while arsenocholine and arsenosu- been described in previous cases of fatal arsenic poison-
gars are metabolised, toxic inorganic arsenic species are ing.12,19 His apparent wellness prior to his sudden death
not among the metabolites.13 The results from the urine is also consistent with arsenic poisoning since death
speciation undertaken in this case show arsenobetaine may be preceded by a period of perceived
in relatively low concentrations so excluding seafood as wellness.11,13,17
the source of arsenic. In the case presented, there were relatively few post-
The high concentrations of inorganic As3þ and mortem findings compared with previous cases in which
5þ
As are suggestive of exposure to inorganic arsenic. generalized oedema, congestion and fluid accumulation
There is individual variation in the ability to methylate of visceral organs and haemorrhagic inflammatory
inorganic arsenic, and there may be a difference in changes in the gastrointestinal tract have been
methylation processes depending on the route of reported.6,17,19 This case differs in that the longitudinal
exposure. In an attempted suicide attempt using hair arsenic concentrations indicate that poisoning
arsenic trioxide, trivalent arsenic was the major peak took place over an extended time period whereas
514 Annals of Clinical Biochemistry 52(4)

most post-mortem reports in cases of arsenic poisoning 4. Hansen HR, Raab A, Jaspers M, et al. Sulfur containing
have been reported following death from acute arsenical mistaken for dimethylarsinous acid [DMA(III)]
exposure. and identified as a natural metabolite in urine: major
In order to conclude that arsenic poisoning is as a implications for studies on arsenic metabolism and tox-
icity. Chem Res Toxicol 2004; 17: 1086–1091.
result of intentional poisoning, three specific criteria
5. Mackell MA, Gantner GE, Poklis A, et al. An unsus-
must be satisfied: that arsenic is present in toxic con- pected arsenic poisoning murder disclosed by forensic
centrations in tissues, its presence could not be autopsy. Am J Forsenic Med Pathol 1985; 6: 358–361.
accounted for by alternative incidental possibilities 6. Adelson L. The pathology of homicide. Springfield: CC
and that the observed symptoms are consistent with Thomas, 1974.
previously reported fatal cases.37 In this case, all the 7. Rehling CJ. P363-386. In: Stolman A (ed.) Progress in
three conditions were satisfied and so it was concluded chemical toxicology, vol 3. New York and London:
that death was a result of intentional fatal arsenic poi- Academic Press, 1967.
soning. Arsenic is readily purchased in the countries the 8. Watanabe C, Inaoka T, Kadona T, et al. Males in rural
patient had visited being the toxic agent in many roden- Bangladeshi communities are more susceptible to chronic
ticides. Arsenic poisoning occurred over a period of arsenic poisoning than females: analyses based on urinary
arsenic. Environ Health Perspect 2001; 109: 1265–1270.
around two months making suicide unlikely.
9. Buchet JP, Lauwerys R and Roels H. Comparison of the
urinary excretion of arsenic metabolites after a single oral
Acknowledgements dose of sodium arsenite, monomethylarsonate, or
Dimethylthioarsenic was synthesised and kindly gifted by dimethylarsinate in man. Int Arch Occup Environ Health
Kevin Francesconi (University of Graz, Austria). 1981; 48: 71–79.
10. Johnson LR and Farmer JG. Use of human metabolic
studies and urinary arsenic speciation in assessing arsenic
Declaration of conflicting interest exposure. Bull Environ Contam Toxicol 1991; 46: 53–61.
None. 11. Bolliger CT, van Zijl P and Louw JA. Multiple organ
failure with the adult respiratory distress syndrome in
homicidal arsenic poisoning. Respiration 1992; 59: 57–61.
Funding 12. Massey EW. Arsenic poisoning. South Med J 1981; 74:
None. 88.
13. Norin H and Vahter M. A rapid method for the selective
analysis of total urinary metabolites of inorganic arsenic.
Ethical Approval Scand J Work Environ Health 1981; 7: 38–44.
The North Glasgow Hospitals Trust Ethics Group confirmed 14. Pounds CA. Quantitation in arsenical poisoning and its
that ethical approval was not required. potential forensic significance. MPhil Thesis, University
of Surrey, Aldermaston, 1978.
15. Lander HL and Crisp CS. Arsenic in the hair and nails.
Guarantor Its significance in acute arsenical poisoning. J Forsenic
AD. Med 1965; 12: 52.
16. Morton J, Carolan VA and Gardiner PHE. Removal of
exogenously bound elements from human hair by various
Contributorship washing procedures and determination by inductively
couple plasma mass spectrometry. Anal Chim Acta
AD performed the initial arsenic analysis and wrote the
2002; 455: 23–34.
manuscript. JM and EL provided Figure 1 and performed
17. Adelson L. Homicidal arsenic poisoning. Medicolegal
the speciation analysis and checked the final manuscript.
investigation of four cases. Postgrad Med 1966; 39:
AT provided expert advice and checked the manuscript.
A46–86.
JMcA provided forensic and post-mortem information and
18. Solomons ET and Walls HC. Analysis of arsenic infor-
checked the final manuscript. SA provided clinical informa-
ensic cases utilizing a rapid, non-ashing technique and
tion and checked the final manuscript.
furnace atomic absorption. J Anal Toxicol 1983; 7:
220–222.
References 19. Poklis A and Saady JJ. Arsenic poisoning: acute or
1. Heitland P and Koster HD. Comparison of different med- chronic? Suicide or murder? Am J Forsenic Med Pathol
ical cases in urinary arsenic speciation by fast HPLC-ICP- 1990; 11: 226–232.
MS. Int J Environ Health 2009; 212: 432–438. 20. LeBeau MA, Mongomery MA and Brewer JD. The role
2. Roy A. Old textbooks out for arsenic poisoning case. of variations in growth rate and sample collection on
Sunday Telegraph, 28 December 1995. interpreting results of segmental analyses of hair.
3. Leese E, Morton J, Tan E, et al. Microlitre ICP-MS deter- Forensic Sci Int 2011; 210: 110–116.
minations of unexposed UK urinary arsenic speciation ref- 21. Versieck J. Trace elements in human body fluids and tis-
erence values. J Anal Toxicol 2014; 38: 24–30. sues. Crit Rev Clin Lab Sci 1985; 22: 97–184.
Duncan et al. 515

22. Bednarczyk LR and Matusiak W. Case report: an arsenic exposed areas of Pakistan. Biol Trace Elem Res 2011; 144:
murder. J Anal Toxicol 1982; 6: 260–261. 86–96.
23. Benramdane L, Accominotti M, Fanton L, et al. Arsenic 31. Hata A, Yamanaka K, Habib MA, et al. Arsenic speci-
speciation in human organs following fatal arsenic triox- ation analysis of urine samples from individuals living in
ide poisoning: a case report. Clin Chem 1999; 45: an arsenic-contaminated area in Bangladesh. Environ
301–306. Health Prevent Med 2012; 17: 235–245.
24. Wu J, Shao Y, Liu J, et al. The medicinal use of realgar 32. Ahsan H, Perrin M, Rahman A, et al. Associations
(As4S4) and its recent development as an anticancer between drinking water and urinary arsenic levels and
agent. J Ethno Pharmacol 2011; 135: 595–602. skin lesions in Bangladesh. J Occup Environ Med 2000;
25. Heitland P and Koster HD. Fast determination of arsenic 42: 1195–1201.
species and total arsenic in urine by HPLC-ICP-MS: con- 33. Argos M, Kalra T, Pierce BL, et al. A prospective study
centration ranges for unexposed German inhabitants and of arsenic exposure from drinking water and incidence of
clinical case studies. J Anal Toxicol 2008; 32: 308–314. skin lesions in Bangladesh. Am J Epidemiol 2011; 174:
26. Cullen WR and Reimer KJ. Arsenic speciation in the 185–194.
environment. Chem Rev 1989; 89: 713–764. 34. Yoshida T, Yamauchi H and Sun GF. Chronic health
27. Naranmandura H, Ogra Y, Iwata K, et al. Evidence of effects in people exposed to arsenic via the drinking
toxicity differences between inorganic arsenite and water: dose-response relationships in review. Toxicol
thioarsenicals in human bladder cancer cell. Toxicol Appl Pharmacol 2004; 198: 243–252.
Appl Pharmacol 2009; 238: 133–140. 35. Schoolmeester WL and White DR. Arsenic poisoning.
28. Rehman K and Naranmandura H. Arsenic metabolism South Med J 1980; 73: 198–208.
and thioarsenicals. Metallomics 2012; 4: 881–892. 36. Arup P, Chowdry UK, Mondal B, et al. Arsenic burden
29. Baig JA, Kazi TG, Shah AQ, et al. Evaluation of toxic from cooked rice in the populations of arsenic affected
risk assessment of arsenic in male subjects through drink- and nonaffected areas and Kolkata city in West Bengal,
ing water in southern Sindh Pakistan. Biol Trace Elem India. Environ Sci Technol 2009; 43: 3349–3355.
Res 2011; 143: 772–786. 37. Trestrail J. Criminal poisoning: an investigational guide for
30. Wadhwa SK, Kazi TG, Chandio AA, et al. Comparative law enforcement, toxicologists, forensic scientists, and
study of liver cancer patients in arsenic exposed and non- attorneys. Clifton: Humana Press, 2007.