Case Report
Annals of Clinical Biochemistry
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
In the past, arsenic has been a popular choice of poison
used for suicide and homicide; however, more recently
its availability in UK and USA has been restricted.
Only two cases of intentional arsenic poisoning have
been reported in the western literature since 1992.1,2
We present a recent case of unexplained sudden
death. The case was reported to the Procurator Fiscal
(Scottish equivalent to the Coroner), and a diagnostic
forensic process was instigated that supported the con-
clusion that the man died as a direct result of maleficent
arsenic poisoning.
Case report
A 50-year-old man of Pakistani origin who had been
living in Saudi Arabia with relatives for three months,
presented with a six-week history of diarrhoea and
vomiting. He also reported general malaise, abdominal
tenderness, mild fever, numbness in his arms and legs
and blurring of vision. He had lost approximately 15 kg
in weight. When his symptoms began, he had volun-
teered to his partner, a nephew and a friend that he
2015, Vol. 52(4) 510–515
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DOI: 10.1177/0004563214559222
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thought he may have been poisoned as he had felt
unwell following a meal.
He returned to the UK via Pakistan where he again
visited relatives. In Pakistan, he presented to a local
hospital with diarrhoea and vomiting. He was diag-
nosed with Helicobacter pylori infection and was com-
menced on H. pylori eradication therapy. After
returning to the UK and around seven weeks after
the onset of his illness, he presented to his GP with
diarrhoea, vomiting and a tender abdomen. The patient
was referred to hospital.
1
Scottish Trace Element & Micronutrient Reference Laboratory, Glasgow
Royal Infirmary, Glasgow, UK
2
Department of Clinical Chemistry, Royal Surrey County Hospital,
Guildford, UK
3
Health and Safety Laboratory, Buxton, UK
4
University Hospital Crosshouse, Crosshouse, UK
5
Forensic Medicine and Science, Glasgow University, Glasgow, UK
Corresponding author:
Andrew Duncan, Scottish Trace Element & Micronutrient Reference
Laboratory, Glasgow Royal Infirmary, Glasgow G4 0SF, UK.
Email: Andrew.duncan@ggc.scot.nhs.uk
Duncan et al.
There was no significant medical history, but the
patient had been shot in the leg, allegedly by a relative
during a trip to Pakistan around a year before his
death.
On general examination, he looked well. His tem-
perature, pulse, blood pressure, respiratory rate and
oxygen saturations were normal. He had moderate ten-
derness over the right hypochondrium.
Laboratory findings on admission showed pancyto-
penia and deranged liver function tests (reference
ranges in parentheses): haemoglobin 117 g/L (130–
180 g/L), white blood cells 1.0  109/L (4–11  109/L);
platelets 95  109/L (150–400  109/L); mean cell
volume 80 fL (78–99 fL); neutrophils 0.4  109/L
(2–7.5  109/L); lymphocytes 0.4  109/L (1.5–4  109/
L); vitamin B12 1053 ng/L (200–900 ng/L); folate
4.3 mg/L (3.1–20 mg/L); ferritin 422 mg/L (10–275 mg/L);
urea 10.3 mmol/L (2.5–7.8 mmol/L); creatinine
122 mmol/L (40–130 mmol/L); total bilirubin 46 mmol/L
(<20 mmol/L); alkaline phosphatase 70 U/L (30–130 U/
L); aspartate aminotransferase 78 U/L (<40 U/L); ala-
nine aminotransferase 103 U/L (<50 U/L); calcium
2.15 mmol/L (2.2–2.5 mmol/L); phosphate 1.83 mmol/
L (0.8–1.5 mmol/L); C-reactive protein 16 mg/L
(<10 mg/L); lactate 1.5 mmol/L (0.5–2.2 mmol/L); and
amylase 98 U/L (<10 U/L).
Tests for HIV-antigen/antibody, hepatitis Bs-anti-
gen, hepatitis C antibody, malaria blood film and anti-
gen, anti-nuclear antibodies, mitochondrial antibody
and smooth muscle antibody were all negative. A
blood film showed moderate anisocytosis with some
polychromasia. There was marked leucopenia and
thrombocytopenia. The chest X-ray was normal.
Abdominal ultrasound reported a trace of free fluid
within the pelvic cavity. An electrocardiography was
scheduled for the following morning; however, that
morning the patient was found deceased hanging over
the side of his bed. The patient was already cold and
resuscitation was not attempted. The case was referred
Table 1. Concentrations of arsenic species in a post-mortem urine sample.
Arsenic concentration
Urinary arsenic species (mmol/L)
Arsenic3þ 5.5 (8.5%)
Arsenic5þ 2.4 (3.7%)
Monomethyl arsenic 1.2 (1.9%)
Dimethyl arsenic 17.5 (27.1%)
Arsenobetaine 0.07 (0.1%)
Dimethylthio arsenic Approximately 38 (58.6%)a
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.
511
to the Procurator Fiscal (Scotland), and a post-mortem
examination was instructed.
At post-mortem, there were few pathological find-
ings. External examination revealed petechial haemor-
rhages in and around the eyes, in the mouth and over the
trunk and right upper arm and an area of darker brown
discolouration of the skin over the back. Internally, there
were bilateral pleural effusions, the trachea contained a
large amount of frothy fluid and there was non-specific
pulmonary congestion and oedema. The liver was con-
gested reflecting the deranged liver function tests, and
there was focal reddening of the lining of the ascending
colon, the remainder of the gastrointestinal tract being
normal. Microscopy revealed very occasional contrac-
tion bands in the myocardium and some scattered
mixed inflammatory cells in the liver sinusoids, but no
unequivocal hepatocyte necrosis. Several oval scars were
present on the front of each thigh. The entire body was
X-rayed prior to post-mortem, and pieces of lead shot
were subsequently retrieved from the right thigh and
scrotum. No Geiger counter was used.
Samples of liver, urine, blood and hair were collected
for routine toxicology and toxic trace element analysis.
Arsenic, lead, mercury and thallium were measured by
inductively-coupled plasma mass spectrometry (ICP-
MS). Concentrations of lead, mercury and thallium
were within reference limits but arsenic was grossly ele-
vated in all samples (Table 1): blood, 7.0 mmol/L (refer-
ence range <0.135 mmol/L); urine, 64.5 mmol/L
(reference range <0.25 mmol/L); liver, 39 mg/g; 3 mm sec-
tions of hair from root end, 71, 74, 44, 24, 14, 11, 10, and
11 mg/g (reference range <0.5 mg/g). The latter showed a
gradual increase in arsenic exposure over time with high-
est concentrations in the month before his death.
Speciation of arsenic in urine was performed by
micro flow liquid chromatography coupled to ICP-
MS3 (see Figure 1). The peak fraction which was
unidentified was collected by high-performance liquid
chromatography and analysed by micro liquid
Reference range Reference range
95th percentile Arsenic concentration 95th percentile
(mmol/L) (mmol/mol creatinine) (mmol/mol creatinine)
0.007 983 <0.99
0.003 421 <0.35
0.03 219 <3.1
0.17 3122 <16.1
1.7 12 <175
Not known Approximately 6750a Not known
512
chromatography-ICP-MS and electro-spray ionisation-
tandem mass spectrometry. The mass spectrum of this
peak showed a fragmentation pattern that was similar
to the mass spectrum obtained from dimethylthioarse-
nic ((CH3)2As(S)O). The mass spectrum results are also
consistent with a previous study of dimethylthioarsenic
identification.4
Discussion
This patient’s blood arsenic result of 7 mmol/L was sub-
stantially higher than our upper reference limit of
0.135 mmol/L but considerably lower than other fatal
cases of arsenic poisoning, for example 96 mmol/L5 in
one case, an average of 49 mmol/L (range: 4 to
267 mmol/L) reported in a series of 19 victims6 and
144 mmol/L (range: 8 to 1802 mmol/L) in a subsequent
series of 18 victims.7 However, the time from poisoning
to blood collection was not quoted in these studies and
since the half-life of arsenic in vivo is around 48 h,8 blood
concentrations fall quickly. Consequently, blood taken
on the day of poisoning shows much higher concentra-
tions than samples taken several days later as was the
case in the present report in which three days passed
between leaving Pakistan and his death.
Urine arsenic concentrations fall quickly after a
single arsenic exposure9,10 and so interpretation is dif-
ficult. The victim had a post-mortem urine arsenic con-
centrations of 65.4 mmol/L compared to 49.9 mmol/L
found in another fatal case although in the current
case, the time from exposure was indeterminate and
in the latter was not recorded. In two other severe but
ultimately non-fatal cases, concentrations of 70.8 and
77.4 mmol/L were found on the day of exposure.11 A
concentration of 2777 mmol/L was found in one non-
fatal case in which the sample was collected the day
after poisoning12 and in a failed suicide attempt the
urine concentration was found to be 734 mmol/L only
Figure 1. Arsenic speciation chromatogram of post-mortem urine sample.
DMA: dimethylarsinous acid.
Annals of Clinical Biochemistry 52(4)
3–4 h after exposure.13 Even with relatively low arsenic
exposure, urine concentrations may be high in urine
that has been collected soon after ingestion; for exam-
ple, six healthy volunteers had urine arsenic concentra-
tions of up to 37 mmol/L 10 h after a relatively small
bolus dose of 6 mg arsenic trioxide.14
The main factors affecting arsenic concentrations in
blood and urine are the time from poisoning to sample
collection and the amount of arsenic consumed.
Unfortunately, very few publications document the
former and the latter is rarely known. Since the half-
life of arsenic in these samples is very short, concentra-
tions will decrease rapidly over a brief time period. For
this reason, it is only possible to make limited infer-
ences from blood and urine concentrations.
The incorporation of trace elements in hair, finger-
nails (not collected in this case) and liver is more likely
to be in proportion to the systemic burden and so com-
parison of arsenic concentrations in these tissues with
reported fatal poisonings is likely to be a more reliable
means of assessing degree of exposure.
Measurement of trace elements in longitudinal sec-
tions of hair has been used to gauge the approximate
time course of exposure using the known growth rate of
hair per month. Acute arsenic poisoning may be asso-
ciated with excessive sweating, and in such cases, con-
centrations of arsenic in hair may be due to
contamination of arsenic in sweat as well as incorpor-
ation systemically so making interpretation more diffi-
cult.15 However, in the current case, excessive sweating
was not reported and so longitudinal hair analysis was
undertaken. A head hair arsenic concentration of 71 mg/
g (reference values <0.15 mg/g16) was found in the 3-
mm head hair sample cut closest to the scalp. This is
high and in keeping with previous reports of fatal
arsenic poisonings, for example 10, 94, 147 and
400 mg/g found in four cases17,18 and results from 28
to 226 mg/g and 7.4 to 37 mg/g in sections along the
Duncan et al.
length of hair in two case reports.17,19 The victim’s hair
was 25 mm long representing around the last 10 weeks
of his life based on an average growth rate of approxi-
mately 10.6 mm/month.20 Arsenic concentrations were
high along the length suggesting he had been poisoned
over this entire time period. This is in accord with the
duration of his symptoms which started approximately
70 days before his death. Unfortunately, his hair was
not long enough to give an indication of when the
exposure started. The arsenic concentrations increased
incrementally from the distal end along the 3 mm
lengths of hair analysed, suggesting that the amount
of arsenic absorbed increased over time. This is also
consistent with the chronic presentation of his
symptoms.
The liver arsenic concentration in this case was
39 mg/g (reference range: <0.013 mg/g21). Previous
reports of fatal arsenic poisoning reported liver concen-
trations of 15 mg/g,5 30 mg/g,22 226 mg/g,19 147 mg/g23
and an average of 81.7 mg/g (range: 5 to 400 mg/g) in a
series of 19 cases.7
The arsenic concentrations found in the blood,
urine, liver and hair tissues collected are therefore in
keeping with previously reported cases of fatal arsenic
poisoning. Such concentrations could be achieved acci-
dentally through inadvertent exposure from food,
water, medication or in the workplace. However, the
victim was a businessman and not occupationally
exposed in processes, such as semiconductor manufac-
ture, academic research, use of arsenic containing wood
preservative or other work in which arsenic is used, nor
was he being treated with an arsenical medication.24
The concentration of arsenic is negligible in food-
stuffs with the exception of seafoods in which it may
be as high as 27 mg/g in the case of oysters and 40 mg/g
in seabass. Consequently, following a fish or shellfish
meal, high concentrations in excess of 13 mmol/L23 and
29 mmol/L25 (reference limit <0.25 mmol/L) have been
reported. The main food sources of arsenic are in the
form of non-toxic compounds; arsenobetaine and
arsenocholine in fish and shellfish and arsenosugars in
seaweed. Arsenobetaine is rapidly excreted unchanged
in the urine,26 and while arsenocholine and arsenosu-
gars are metabolised, toxic inorganic arsenic species are
not among the metabolites.13 The results from the urine
speciation undertaken in this case show arsenobetaine
in relatively low concentrations so excluding seafood as
the source of arsenic.
The high concentrations of inorganic As3þ and
5þ
As are suggestive of exposure to inorganic arsenic.
There is individual variation in the ability to methylate
inorganic arsenic, and there may be a difference in
methylation processes depending on the route of
exposure. In an attempted suicide attempt using
arsenic trioxide, trivalent arsenic was the major peak
513
but in an inhaled dust exposure more that 50% of the
total arsenic was methylated in the urine sample.25
In the present case, very high concentrations of both
monomethyl arsenic and dimethyl arsenic were
detected indicating considerable detoxification of inor-
ganic arsenic by methylation had occurred. The
unidentified peak was thought to be dimethylthioarse-
nic which has a high degree of cytotoxicity being pos-
sibly more toxic than arsenite.27 Although biological
pathways are not fully understood, current research
suggests dimethylthioarsenic is produced following
exposure to inorganic arsenic.28
The victim had spent time in Pakistan where concen-
trations of inorganic arsenic in water from bore wells
are elevated compared to the UK.29,30 For example, in
a report of 330 Pakistani subjects, the median urine
concentration was 1.6 mmol/L in exposed individuals
but these ranged up to 28.9 mmol/L (2166 mg/L).31 In
another study, urine concentrations as high as
24.6 mmol/L were found.32 Although urine arsenic con-
centrations are usually lower than those found in fatal
poisoning, on occasions this is not the case. However,
individuals imbibing arsenic in drinking water over
long time periods have chronic exposure resulting in
skin pigmentation, keratosis and increased risk of
skin cancer.33,34 In addition, an inconceivably high
volume of water would have to be drunk in order to
accumulate an acute lethal dose estimated to be 100 to
300 mg35; in the two studies mentioned above, the max-
imum arsenic concentrations in water were 332 mg/L
and 1840 mg/L. Rice grown and cooked in arsenic-
containing water has also been shown to have high
inorganic arsenic concentrations (up to 482 mg/g).36
However, again this would result in chronic arsenic
poisoning and unrealistically large quantities of rice
would require to be eaten to attain a lethal dose.
The natural history of the case presented is in keep-
ing with an acute arsenic poisoning which is associated
with symptoms of nausea, vomiting, diarrhoea and
often abdominal pain, tachycardia and profound hypo-
tension.15 The victim also gave a history of weight loss
and peripheral neurological symptoms which have also
been described in previous cases of fatal arsenic poison-
ing.12,19 His apparent wellness prior to his sudden death
is also consistent with arsenic poisoning since death
may be preceded by a period of perceived
wellness.11,13,17
In the case presented, there were relatively few post-
mortem findings compared with previous cases in which
generalized oedema, congestion and fluid accumulation
of visceral organs and haemorrhagic inflammatory
changes in the gastrointestinal tract have been
reported.6,17,19 This case differs in that the longitudinal
hair arsenic concentrations indicate that poisoning
took place over an extended time period whereas
514
most post-mortem reports in cases of arsenic poisoning
have been reported following death from acute
exposure.
In order to conclude that arsenic poisoning is as a
result of intentional poisoning, three specific criteria
must be satisfied: that arsenic is present in toxic con-
centrations in tissues, its presence could not be
accounted for by alternative incidental possibilities
and that the observed symptoms are consistent with
previously reported fatal cases.37 In this case, all the
three conditions were satisfied and so it was concluded
that death was a result of intentional fatal arsenic poi-
soning. Arsenic is readily purchased in the countries the
patient had visited being the toxic agent in many roden-
ticides. Arsenic poisoning occurred over a period of
around two months making suicide unlikely.
Acknowledgements
Dimethylthioarsenic was synthesised and kindly gifted by
Kevin Francesconi (University of Graz, Austria).
Declaration of conflicting interest
None.
Funding
None.
Ethical Approval
The North Glasgow Hospitals Trust Ethics Group confirmed
that ethical approval was not required.
Guarantor
AD.
Contributorship
AD performed the initial arsenic analysis and wrote the
manuscript. JM and EL provided Figure 1 and performed
the speciation analysis and checked the final manuscript.
AT provided expert advice and checked the manuscript.
JMcA provided forensic and post-mortem information and
checked the final manuscript. SA provided clinical informa-
tion and checked the final manuscript.
References
1. Heitland P and Koster HD. Comparison of different med-
ical cases in urinary arsenic speciation by fast HPLC-ICP-
MS. Int J Environ Health 2009; 212: 432–438.
2. Roy A. Old textbooks out for arsenic poisoning case.
Sunday Telegraph, 28 December 1995.
3. Leese E, Morton J, Tan E, et al. Microlitre ICP-MS deter-
minations of unexposed UK urinary arsenic speciation ref-
erence values. J Anal Toxicol 2014; 38: 24–30.
Annals of Clinical Biochemistry 52(4)
4. Hansen HR, Raab A, Jaspers M, et al. Sulfur containing
arsenical mistaken for dimethylarsinous acid [DMA(III)]
and identified as a natural metabolite in urine: major
implications for studies on arsenic metabolism and tox-
icity. Chem Res Toxicol 2004; 17: 1086–1091.
5. Mackell MA, Gantner GE, Poklis A, et al. An unsus-
pected arsenic poisoning murder disclosed by forensic
autopsy. Am J Forsenic Med Pathol 1985; 6: 358–361.
6. Adelson L. The pathology of homicide. Springfield: CC
Thomas, 1974.
7. Rehling CJ. P363-386. In: Stolman A (ed.) Progress in
chemical toxicology, vol 3. New York and London:
Academic Press, 1967.
8. Watanabe C, Inaoka T, Kadona T, et al. Males in rural
Bangladeshi communities are more susceptible to chronic
arsenic poisoning than females: analyses based on urinary
arsenic. Environ Health Perspect 2001; 109: 1265–1270.
9. Buchet JP, Lauwerys R and Roels H. Comparison of the
urinary excretion of arsenic metabolites after a single oral
dose of sodium arsenite, monomethylarsonate, or
dimethylarsinate in man. Int Arch Occup Environ Health
1981; 48: 71–79.
10. Johnson LR and Farmer JG. Use of human metabolic
studies and urinary arsenic speciation in assessing arsenic
exposure. Bull Environ Contam Toxicol 1991; 46: 53–61.
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.
12. Massey EW. Arsenic poisoning. South Med J 1981; 74:
88.
13. Norin H and Vahter M. A rapid method for the selective
analysis of total urinary metabolites of inorganic arsenic.
Scand J Work Environ Health 1981; 7: 38–44.
14. Pounds CA. Quantitation in arsenical poisoning and its
potential forensic significance. MPhil Thesis, University
of Surrey, Aldermaston, 1978.
15. Lander HL and Crisp CS. Arsenic in the hair and nails.
Its significance in acute arsenical poisoning. J Forsenic
Med 1965; 12: 52.
16. Morton J, Carolan VA and Gardiner PHE. Removal of
exogenously bound elements from human hair by various
washing procedures and determination by inductively
couple plasma mass spectrometry. Anal Chim Acta
2002; 455: 23–34.
17. Adelson L. Homicidal arsenic poisoning. Medicolegal
investigation of four cases. Postgrad Med 1966; 39:
A46–86.
18. Solomons ET and Walls HC. Analysis of arsenic infor-
ensic cases utilizing a rapid, non-ashing technique and
furnace atomic absorption. J Anal Toxicol 1983; 7:
220–222.
19. Poklis A and Saady JJ. Arsenic poisoning: acute or
chronic? Suicide or murder? Am J Forsenic Med Pathol
1990; 11: 226–232.
20. LeBeau MA, Mongomery MA and Brewer JD. The role
of variations in growth rate and sample collection on
interpreting results of segmental analyses of hair.
Forensic Sci Int 2011; 210: 110–116.
21. Versieck J. Trace elements in human body fluids and tis-
sues. Crit Rev Clin Lab Sci 1985; 22: 97–184.
Duncan et al.
22. Bednarczyk LR and Matusiak W. Case report: an arsenic
murder. J Anal Toxicol 1982; 6: 260–261.
23. Benramdane L, Accominotti M, Fanton L, et al. Arsenic
speciation in human organs following fatal arsenic triox-
ide poisoning: a case report. Clin Chem 1999; 45:
301–306.
24. Wu J, Shao Y, Liu J, et al. The medicinal use of realgar
(As4S4) and its recent development as an anticancer
agent. J Ethno Pharmacol 2011; 135: 595–602.
25. Heitland P and Koster HD. Fast determination of arsenic
species and total arsenic in urine by HPLC-ICP-MS: con-
centration ranges for unexposed German inhabitants and
clinical case studies. J Anal Toxicol 2008; 32: 308–314.
26. Cullen WR and Reimer KJ. Arsenic speciation in the
environment. Chem Rev 1989; 89: 713–764.
27. Naranmandura H, Ogra Y, Iwata K, et al. Evidence of
toxicity differences between inorganic arsenite and
thioarsenicals in human bladder cancer cell. Toxicol
Appl Pharmacol 2009; 238: 133–140.
28. Rehman K and Naranmandura H. Arsenic metabolism
and thioarsenicals. Metallomics 2012; 4: 881–892.
29. Baig JA, Kazi TG, Shah AQ, et al. Evaluation of toxic
risk assessment of arsenic in male subjects through drink-
ing water in southern Sindh Pakistan. Biol Trace Elem
Res 2011; 143: 772–786.
30. Wadhwa SK, Kazi TG, Chandio AA, et al. Comparative
study of liver cancer patients in arsenic exposed and non-
515
exposed areas of Pakistan. Biol Trace Elem Res 2011; 144:
86–96.
31. Hata A, Yamanaka K, Habib MA, et al. Arsenic speci-
ation analysis of urine samples from individuals living in
an arsenic-contaminated area in Bangladesh. Environ
Health Prevent Med 2012; 17: 235–245.
32. Ahsan H, Perrin M, Rahman A, et al. Associations
between drinking water and urinary arsenic levels and
skin lesions in Bangladesh. J Occup Environ Med 2000;
42: 1195–1201.
33. Argos M, Kalra T, Pierce BL, et al. A prospective study
of arsenic exposure from drinking water and incidence of
skin lesions in Bangladesh. Am J Epidemiol 2011; 174:
185–194.
34. Yoshida T, Yamauchi H and Sun GF. Chronic health
effects in people exposed to arsenic via the drinking
water: dose-response relationships in review. Toxicol
Appl Pharmacol 2004; 198: 243–252.
35. Schoolmeester WL and White DR. Arsenic poisoning.
South Med J 1980; 73: 198–208.
36. Arup P, Chowdry UK, Mondal B, et al. Arsenic burden
from cooked rice in the populations of arsenic affected
and nonaffected areas and Kolkata city in West Bengal,
India. Environ Sci Technol 2009; 43: 3349–3355.
37. Trestrail J. Criminal poisoning: an investigational guide for
law enforcement, toxicologists, forensic scientists, and
attorneys. Clifton: Humana Press, 2007.