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International Journal of Epidemiology 2000;29:1047–1052
Arsenic-contaminated groundwater has been found in the
US, Taiwan,
1
Mexico,
2
Chile
3,4
and Argentina,
5
but the largest
reported population exposed to inorganic arsenic is in West
Bengal, India and neighbouring Bangladesh.
6
By 1994, inves-
tigators estimated that over 800 000 people in West Bengal
were exposed to elevated inorganic arsenic levels through
drinking water retrieved from tubewells installed in the late
1960s.
7,8
Since the tubewell water was cleaner than surface
water from ponds and the Ganges River, many inhabitants
switched to using well water. The arsenic source is geological,
but controversy exists as to the mechanism whereby inorganic
arsenic mobilizes and becomes transported into the ground-
water from the bedrock of the Gangetic delta.
Hallmark signs of chronic arsenic toxicity include skin kera-
toses of the palms and soles, and hyperpigmentation of the torso
and upper limbs. These skin lesions generally develop 5–10
years after exposure commences, although shorter latencies
are possible. Chronic ingestion of inorganic arsenic causes
© International Epidemiological Association 2000 Printed in Great Britain
Arsenic in drinking water and the prevalence
of respiratory effects in West Bengal, India
Debendra N Guha Mazumder,
a
Reina Haque,
b
Nilima Ghosh,
a
Binay K De,
a
Amal Santra,
a
Dipankar Chakraborti
c
and Allan H Smith
b
Background A large population in West Bengal, India has been exposed to naturally occurring
inorganic arsenic through their drinking water. A cross-sectional survey involv-
ing 7683 participants of all ages was conducted in an arsenic-affected region
between April 1995 and March 1996. The main focus of the study was skin kera-
toses and pigmentation alterations, two characteristic signs of ingested inorganic
arsenic. Strong exposure-response gradients were found for these skin lesions.
The study also collected limited information concerning respiratory system signs
and symptoms, which we report here because increasing evidence suggests that
arsenic ingestion also causes pulmonary effects.
Methods Participants were clinically examined and interviewed, and the arsenic content
in their current primary drinking water source was measured. There were few
smokers and analyses were confined to non-smokers (N = 6864 participants).
Results Among both males and females, the prevalence of cough, shortness of breath,
and chest sounds (crepitations and/or rhonchi) in the lungs rose with increasing
arsenic concentrations in drinking water. These respiratory effects were most
pronounced in individuals with high arsenic water concentrations who also had
skin lesions. Prevalence odds ratio (POR) estimates were markedly increased for
participants with arsenic-induced skin lesions who also had high levels of arsenic
in their current drinking water source (
>500 µg/l) compared with individuals
who had normal skin and were exposed to low levels of arsenic (,50 µg/l).
In participants with skin lesions, the age-adjusted POR estimates for cough were
7.8 for females (95% CI : 3.1–19.5) and 5.0 for males (95% CI : 2.6–9.9); for
chest sounds POR for females was 9.6 (95% CI : 4.0–22.9) and for males 6.9
(95% CI : 3.1–15.0). The POR for shortness of breath in females was 23.2 (95%
CI : 5.8–92.8) and in males 3.7 (95% CI : 1.3–10.6).
Conclusion These results add to evidence that long-term ingestion of inorganic arsenic can
cause respiratory effects.
Keywords Arsenic, respiratory disease, keratoses, hyperpigmentation, cross-sectional study,
drinking water, India
Accepted 13 March 2000
a
Institute of Post Graduate Medical Education and Research, 244 Acharya
Jagadish Chandra Bose Road, Calcutta 700020, India. E-mail: dngm@
apexmail.com
b
School of Public Health, University of California, Berkeley, CA 94720–7360,
USA. E-mail: ahsmith@uclink4.berkeley.edu
c
School of Environmental Studies, Jadavpur University, Calcutta 700032, India.
Corresponding author: DN Guha Mazumder.
1047
non-melanoma skin cancer, and is also associated with
increased risks of cancer of the internal organs.
9
Emerging
evidence shows that ingestion of inorganic arsenic may also
lead to non-malignant respiratory effects.
Respiratory effects in West Bengal were first noted in 1995
when 57% of the 156 patients who lived in arsenic-affected
villages reported having cough.
10
Moreover, epidemiological
studies in Chile have previously suggested an association between
arsenic and non-malignant respiratory effects. From survey
data collected between 1968 and 1972 in Antofagasta, Chile,
Zaldivar and Ghai
11
reported that the prevalence of cough
among 398 children correlated with mean drinking water
arsenic concentrations. In addition, the prevalence of reported
cough declined from 38% to 7% after an arsenic removal plant
was installed in Antofagasta (P , 0.001). Zaldivar
12
also reported
that the prevalence of bronchiectasis was 23-fold greater among
children with arsenic-induced skin lesions living in Antofagasta
compared to children living in the rest of Chile. Rosenberg
13
conducted autopsies on five children who died between 1968
and 1969 in Antofagasta. All five children possessed character-
istic signs of chronic arsenic poisoning, including hyperpig-
mentation and/or keratoses. Lung tissue was examined in four
of these children, with abnormalities found in all four. Inter-
stitial fibrosis was detected in two of the cases. A 1976 cross-
sectional survey in Antofagasta examined 144 schoolchildren
with arsenic-induced skin lesions, and bronchopulmonary
disease occurred 2.5 times more often in these children
(15.9%) compared with children with normal skin (6.9%).
3
In
a recent study, Smith et al.
4
found high relative rates for chronic
obstructive pulmonary disease (COPD) mortality among young
men and women living in the same arsenic-exposed region in
Chile which includes Antofagasta. In those aged 30–39 there
were four deaths from COPD among males (0.8 expected) and
six among women (0.1 expected, SMR [men and women
combined] = 11.1, 95% CI : 5.3–20.4, P , 0.001). Since COPD
mortality was not increased in older age groups, the authors
suggested that exposures during childhood were important and
led to the increased COPD mortality rates in young adults.
A few occupational studies conducted in the 1950s in
Sweden have also reported non-malignant respiratory effects in
copper smelter workers exposed to airborne arsenic. In one
clinical study of 1459 copper smelter workers cited by Gerhard
et al., a syndrome characterized by chronic rhino-pharyngeo-
tracheobronchitis, lesions of the mucous membranes of the
upper respiratory system, emphysema and decreased
pulmonary function was described.
14
Information on smoking
habits was not presented, which might have contributed to the
reported signs and symptoms.
With the exception of the study in Chile, respiratory effects of
ingestion of inorganic arsenic has not been reported elsewhere.
The cross-sectional survey included over 7000 individuals,
one of the largest arsenic-affected populations known to date,
living in the 24 South Parganas, West Bengal. The aim of the
survey, which was conducted between April 1995 and March
1996, was to determine the prevalence of various health effects
associated with arsenic. The most common arsenic-related
health effects found were keratoses and hyperpigmentation
and a clear exposure-response trend was identified according
to arsenic concentrations in drinking water.
15
In this paper,
we focus on the prevalence of respiratory signs and symptoms
assessed in the survey, including cough, chest sounds, and
shortness of breath.
Methods
Study area and population
A survey of one of the arsenic-affected districts south of
Calcutta, the 24 South Parganas, was conducted. Two areas in
this district were targeted; the first included 25 villages and was
selected because high levels of arsenic were reported in some of
the tubewells. In this high exposure area which included
remote rural areas, a convenience sampling strategy was used.
The field team went to the centre of each village, and selected
the most convenient hamlet (group of houses) to begin
sampling. Every member of the household who was present at
the time of interview was invited to participate. Details concern-
ing the participation rate were not recorded, but the response
rate from those invited to participate was excellent with
negligible refusals. An interview and a brief medical exam were
conducted on each participant. Sampling continued house-to-
house until 50 to 150 participants were recruited.
The second area included the remaining part of the district
(32 villages in 16 administrative blocks), where people were
drinking from shallow tubewells. Sampling in this area was
limited to villages with more than 100 households. One or more
villages were randomly selected from each of the 16 blocks,
depending on the population size. One village was targeted
for sampling in a small block, but two or three villages were
selected if the block was larger. In this area, the field team went
to the centre of the village and commenced sampling in the
most convenient hamlet; but this time, residents of every fourth
house were invited to participate. These two areas combined
have a population of 150 457.
In all 7818 individuals participated in the survey. Arsenic
levels in the drinking water sources were measured for 7683
individuals (4093 females and 3590 males). There were few
smokers and they were excluded from the analyses presented
here; thus 6864 participants (4042 females and 2822 males)
comprise the study population for consideration of respiratory
signs and symptoms.
Interview and clinical exam
Participants were briefly questioned about their sources of drink-
ing water and socio-demographic characteristics. Participants
were then asked to volunteer any health problems. If the
participant did not volunteer any information concerning the
presence of respiratory problems, they were then specifically
asked by a physician interviewer the following questions:
‘Do you have problems with coughing? Do you have problems
with shortness of breath?’ Chest sounds were determined by
auscultation and included crepitations and/or rhonchi. In view
of the potential relationship between reported shortness of
breath and general weakness, the present analysis also included
responses to the question, ‘Are you troubled with feeling weak?’
A general medical examination was also performed, including
a careful examination for skin lesions. A detailed explanation
of the criteria used for diagnosing keratoses and hyper-
pigmentation appears elsewhere.
15
Physician interviewers who
were blind to the arsenic content in the drinking water
diagnosed the skin lesions. Arsenic-induced skin lesions are
1048 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
distinctive. Diffuse keratoses appear as bilateral thickening of
the palms and soles. Nodular keratoses occur as small
protrusions on the palms and soles, with or without nodules on
the dorsum of the hands, feet or legs. Raindrop-shaped
discoloured spots, diffuse dark spots, or diffuse darkening of the
skin on the limbs and trunk mark changes in pigmentation due
to arsenic.
Participants were also asked if they smoked currently or had
smoked in the past. In rural India, small hand-rolled cigarettes
(biris) are most frequently consumed. Biris are usually filterless
and are about an inch and half in length. The 819 participants
(768 males and 51 females) who reported they had smoked
regularly or often, either currently or in the past, were excluded
from consideration because of relatively small numbers and
potential confounding.
Arsenic measurements in drinking water
Water samples were obtained from the main private or public
tubewells used for drinking by each household. Arsenic con-
centration was measured by flow-injection hydride generation
atomic absorption spectrophotometry. The detection limit
determined at the 90% confidence level was 3 µg/l.
16
Statistical analyses
The outcomes analysed included participant-reported cough,
shortness of breath, and weakness, and the presence of chest
sounds recorded by the examining physician. To allow for direct
comparisons without the distorting effects of age, the preval-
ence of each outcome was directly standardized to the age
distribution of all study participants of the same sex. Each out-
come was examined according to arsenic levels in the tubewell
drinking water source used by each participant. The tubewells
were categorized according to arsenic concentrations as follows:
,50, 50–199, 200–499, 500–799 and >800 µg/l.
Tests for trend in proportions using the midpoints of the ex-
posure categories were based on the χ
2
distribution.
17
In view
of unidirectional a priori hypotheses, one-sided P-values are
presented for the test of trend.
Prevalence odds ratios (POR) were also calculated for each
outcome comparing those with very high exposure to arsenic
in drinking water (>500 µg/l) with those with the lowest
exposures (,50 µg/l). The Mantel-Haenszel method was used
to adjust for age. Data were also stratified by the presence or
absence of arsenic-caused lesions.
Results
Trends by arsenic concentrations in drinking water
Table 1 presents the age and sex distribution of all non-smoking
participants by arsenic levels in drinking water. The arsenic
concentration in the tubewell water samples ranged from
,3 µg/l to 3400 µg/l.
Tables 2–4 present findings for cough, chest sounds and short-
ness of breath. Among females, the overall age-adjusted pre-
valence for each respiratory outcome (cough, chest sounds
and shortness of breath) was close to 2.5 per 100. Clear trends
of increasing prevalence by arsenic water concentration can be
seen for cough (Table 2, test for trend P , 0.0001) and chest
sounds (Table 3, test for trend P = 0.002). However, the preval-
ence of shortness of breath showed a markedly non-linear
relationship (P , 0.0001) peaking in the third exposure category
(200–499 µg/l), but declining sharply thereafter to almost base-
line levels.
Among males, the overall age-adjusted prevalence of cough
(5.2 per 100) and chest sounds (4.4 per 100) was nearly twice
ARSENIC AND RESPIRATORY EFFECTS 1049
Table 1 Distribution of non-smoking participants by age, sex and
arsenic level in drinking water (µg/l)
Arsenic level (µg/l)
Age group ,50 50–199 200–499 500–799 >800 Total
Females
<9 194 107 134 75 26 536
10–19 399 186 173 65 26 849
20–29 572 275 197 83 23 1150
30–39 304 172 119 44 15 654
40–49 168 78 55 28 9 338
50–59 156 74 43 29 11 313
>60 94 52 41 9 6 202
All ages 1887 944 762 333 116 4042
Males
<9 220 156 128 81 28 613
10–19 313 166 144 62 29 714
20–29 292 140 96 50 20 598
30–39 147 84 79 38 15 363
40–49 78 58 45 14 5 200
50–59 65 31 35 18 8 157
>60 82 48 31 12 4 177
All ages 1197 683 558 275 109 2822
Table 2 Prevalence of cough per 100 by age group and arsenic level
(µg/l) among non-smokers, with number of cases in parentheses
Arsenic level (µg/l)
Age group ,50 50–199 200–499 500–799 >800 Total
Females
<9 0.5 (1) 0.9 (1) 1.5 (2) 2.7 (2) 0.0 (0) 1.1 (6)
10–19 1.8 (7) 0.5 (1) 1.7 (3) 3.1 (2) 7.7 (2) 1.8 (15)
20–29 1.7 (10) 0.7 (2) 1.5 (3) 3.6 (3) 4.3 (1) 1.7 (19)
30–39 2.6 (8) 2.3 (4) 2.5 (3) 0.0 (0) 6.7 (1) 2.4 (16)
40–49 3.6 (6) 0.0 (0) 3.6 (2) 10.7 (3) 0.0 (0) 3.3 (11)
50–59 5.1 (8) 2.7 (2) 4.7 (2) 17.2 (5) 9.1 (1) 5.8 (18)
>60 3.2 (3) 5.8 (3) 9.8 (4) 11.1 (1) 16.7 (1) 5.9 (12)
All ages 2.3 (43) 1.4 (13) 2.5 (19) 4.8 (16) 5.2 (6) 2.4 (97)
Age-adjusted 2.2 1.3 2.6 4.9 5.5 2.4
Males
<9 1.8 (4) 0.6 (1) 0.8 (1) 1.2 (1) 3.6 (1) 1.3 (8)
10–19 1.6 (5) 1.2 (2) 4.2 (6) 1.6 (1) 13.8 (4) 2.5 (18)
20–29 5.5 (16) 5.0 (7) 6.3 (6) 6.0 (3) 15.0 (3) 5.9 (35)
30–39 6.1 (9) 8.3 (7) 8.9 (7) 10.5 (4) 20.0 (3) 8.3 (30)
40–49 10.3 (8) 3.4 (2) 4.4 (2) 0.0 (0) 20.0 (1) 6.5 (13)
50–59 6.2 (4) 3.2 (1) 11.4 (4) 16.7 (3) 0.0 (0) 7.6 (12)
>60 11.0 (9) 10.4 (5) 6.5 (2) 8.3 (1) 0.0 (0) 9.6 (17)
All ages 4.6 (55) 3.7 (25) 5.0 (28) 4.7 (13) 11.0 (12) 4.7 (133)
Age-adjusted 5.1 4.1 5.5 5.4 11.9 5.2
Females: Test for trend P , 0.0001, test for non-linearity P = 0.03.
Males: Test for trend P = 0.0014, test for non-linearity P = 0.24.
as high as among females, but once again there were trends of
increasing prevalence by water arsenic concentration (Tables 2
and 3). The overall age-adjusted prevalence for shortness of
breath in males (3.6 per 100, Table 4) was higher than in
females (2.6 per 100). As with females, the highest prevalence
of shortness of breath occurred in the water concentration
range of 200–499 µg/l. The prevalence of both cough and chest
sounds increased with increasing water arsenic content in
children of both sexes, especially in age range 10–19 (Tables 2
and 3).
The age-adjusted prevalence of weakness increased strongly
with arsenic water concentrations in both sexes (from 1.7 per
100 to 11.9 per 100 among women, P , 0.0001, and from
0.9 to 9.5 per 100 among men, P , 0.0001, Table 5).
Comparisons between the high and low exposure
groups
Table 6 gives POR comparing the highest exposure category
(>500 µg/l) with the lowest exposure category (,50 µg/l). All
POR are elevated, but particularly so for shortness of breath
among females and weakness in both sexes. Table 6 also
presents POR separately for those with and without arsenic-
caused skin lesions (keratoses and/or pigmentation changes).
Markedly increased POR are seen for each outcome in both
males and females with skin lesions. With the exception of
shortness of breath among women and weakness in both sexes,
there is little to see in the way of effects among participants
without skin lesions.
Finally, the joint occurrence of the outcomes of interest was
examined. The most frequent combination was cough plus chest
sounds. Among those with skin lesions and current drinking
1050 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
Table 3 Prevalence of chest sounds (crepitations and/or rhonchi)
per 100 by age group and arsenic level (µg/l) among non-smokers,
with number of cases in parentheses
Arsenic level (µg/l)
Age group ,50 50–199 200–499 500–799 >800 Total
Females
<9 0.5 (1) 0.9 (1) 3.0 (4) 0.0 (0) 0.0 (0) 1.1 (6)
10–19 1.0 (4) 1.1 (2) 2.3 (4) 1.5 (1) 3.8 (1) 1.4 (12)
20–29 1.4 (8) 0.7 (2) 0.5 (1) 3.6 (3) 4.3 (1) 1.3 (15)
30–39 2.3 (7) 2.3 (4) 3.4 (4) 0.0 (0) 0.0 (0) 2.3 (15)
40–49 5.4 (9) 2.6 (2) 7.3 (4) 10.7 (3) 11.1 (1) 5.6 (19)
50–59 2.6 (4) 8.1 (6) 0.0 (0) 17.2 (5) 9.1 (1) 5.1 (16)
>60 5.3 (5) 5.8 (3) 17.1 (7) 11.1 (1) 33.3 (2) 8.9 (18)
All ages 2.0 (38) 2.1 (20) 3.1 (24) 3.9 (13) 5.2 (6) 2.5 (101)
Age-adjusted 2.0 2.1 3.1 4.2 5.4 2.5
Males
<9 0.5 (1) 1.3 (2) 0.8 (1) 2.5 (2) 0.0 (0) 1.0 (6)
10–19 1.3 (4) 0.6 (1) 4.9 (7) 1.6 (1) 3.4 (1) 2.0 (14)
20–29 4.1 (12) 2.9 (4) 2.1 (2) 4.0 (2) 10.0 (2) 3.7 (22)
30–39 0.0 (0) 3.6 (3) 5.1 (4) 7.9 (3) 0.0 (0) 2.8 (10)
40–49 1.3 (1) 1.7 (1) 11.1 (5) 7.1 (1) 20.0 (1) 4.5 (9)
50–59 9.2 (6) 9.7 (3) 22.9 (8) 33.3 (6) 0.0 (0) 14.6 (23)
>60 14.6 (12) 14.6 (7) 16.1 (5) 8.3 (1) 25.0 (1) 14.7 (26)
All ages 3.0 (36) 3.1 (21) 5.7 (32) 5.8 (16) 4.6 (5) 3.9 (110)
Age-adjusted 3.1 3.5 6.5 6.8 6.6 4.4
Females: Test for trend P = 0.002, test for non-linearity P = 0.37.
Males: Test for trend P = 0.04, test for non-linearity P = 0.018.
Table 4 Prevalence of shortness of breath per 100 by age group and
arsenic level (µg/l) among non-smokers, with number of cases in
parentheses
Arsenic level (µg/l)
Age group ,50 50–199 200–499 500–799 >800 Total
Females
<9 0.0 (0) 0.0 (0) 0.0 (0) 0.0 (0) 0.0 (0) 0.0 (0)
10–19 0.0 (0) 3.2 (6) 5.2 (9) 0.0 (0) 0.0 (0) 1.8 (15)
20–29 0.3 (2) 4.0 (11) 10.2 (20) 1.2 (1) 0.0 (0) 3.0 (34)
30–39 0.7 (2) 4.1 (7) 5.9 (7) 4.5 (2) 0.0 (0) 2.8 (18)
40–49 0.6 (1) 5.1 (4) 3.6 (2) 3.6 (1) 0.0 (0) 2.4 (8)
50–59 0.6 (1) 4.1 (3) 16.3 (7) 17.2 (5) 9.1 (1) 5.4 (17)
>60 2.1 (2) 5.8 (3) 19.5 (8) 11.1 (1) 0.0 (0) 6.9 (14)
All ages 0.4 (8) 3.6 (34) 7.0 (53) 3.0 (10) 0.9 (1) 2.6 (106)
Age-adjusted 0.4 3.5 7.5 3.3 0.7 2.6
Males
<9 0.0 (0) 0.6 (1) 0.8 (1) 1.2 (1) 0.0 (0) 0.5 (3)
10–19 0.6 (2) 4.8 (8) 4.9 (7) 0.0 (0) 3.4 (1) 2.5 (18)
20–29 2.4 (7) 2.1 (3) 2.1 (2) 2.0 (1) 10.0 (2) 2.5 (15)
30–39 2.7 (4) 3.6 (3) 5.1 (4) 2.6 (1) 0.0 (0) 3.3 (12)
40–49 0.0 (0) 8.6 (5) 11.1 (5) 7.1 (1) 20.0 (1) 6.0 (12)
50–59 4.6 (3) 3.2 (1) 22.9 (8) 5.6 (1) 0.0 (0) 8.3 (13)
>60 3.7 (3) 12.5 (6) 16.1 (5) 8.3 (1) 25.0 (1) 9.0 (16)
All ages 1.6 (19) 4.0 (27) 5.7 (32) 2.2 (6) 4.6 (5) 3.2 (89)
Age-adjusted 1.7 4.1 6.5 2.8 6.6 3.6
Females: Test for trend P = 0.02, test for non-linearity P , 0.0001.
Males: Test for trend P = 0.04, test for non-linearity P = 0.0004.
Table 5 Prevalence of weakness per 100 by age group and arsenic
level (µg/l) among non-smokers, with number of cases in parentheses
Arsenic level (µg/l)
Age group ,50 50–199 200–499 500–799 >800 Total
Females
<9 1.0 (2) 0.9 (1) 0.7 (1) 0.0 (0) 3.8 (1) 0.9 (5)
10–19 0.5 (2) 1.1 (2) 1.2 (2) 6.2 (4) 11.5 (3) 1.5 (13)
20–29 1.4 (8) 2.5 (7) 6.1 (12)14.5 (12) 4.3 (1) 3.5 (40)
30–39 1.3 (4) 5.2 (9) 5.0 (6) 4.5 (2) 6.7 (1) 3.4 (22)
40–49 4.8 (8) 5.1 (4) 14.5 (8) 14.3 (4) 22.2 (2) 7.7 (26)
50–59 3.2 (5) 10.8 (8) 4.7 (2)34.5 (10) 27.3 (3) 8.9 (28)
>60 3.2 (3) 5.8 (3) 7.3 (3) 11.1 (1) 50.0 (3) 6.4 (13)
All ages 1.7 (32) 3.6 (34) 4.5 (34) 9.9 (33) 12.1 (14) 3.6 (147)
Age-adjusted 1.7 3.5 4.9 10.7 11.9 3.7
Males
<9 0.5 (1) 0.6 (1) 0.8 (1) 1.2 (1) 0.0 (0) 0.7 (4)
10–19 0.3 (1) 1.8 (3) 0.0 (0) 1.6 (1) 6.9 (2) 1.0 (7)
20–29 0.7 (2) 2.9 (4) 6.3 (6) 6.0 (3) 20.0 (4) 3.2 (19)
30–39 1.4 (2) 4.8 (4) 8.9 (7) 5.3 (2) 13.3 (2) 4.7 (17)
40–49 1.3 (1) 1.7 (1) 6.7 (3) 0.0 (0) 0.0 (0) 2.5 (5)
50–59 1.5 (1) 6.5 (2) 0.0 (0) 11.1 (2) 0.0 (0) 3.2 (5)
>60 2.4 (2) 14.6 (7) 12.9 (4) 16.7 (2) 25.0 (1) 9.0 (16)
All ages 0.8 (10) 3.2 (22) 3.8 (21) 4.0 (11) 8.3 (9) 2.6 (73)
Age-adjusted 0.9 3.6 4.4 4.7 9.5 2.9
Females: Test for trend P , 0.0001, test for non-linearity P = 0.0001.
Males: Test for trend P , 0.0001, test for non-linearity P = 0.01.
water containing .500 µg/l, 5 of the 7 females reporting cough
were also found to have lung chest sounds, as did 6 of the 14
men reporting problems with coughing.
Discussion
This study provides evidence that ingestion of inorganic arsenic
in drinking water results in pulmonary effects manifested by
cough, chest sounds in the lungs and shortness of breath.
With the exception of shortness of breath among females, the
prevalence of each outcome rose with increasing concentrations
of arsenic in the primary drinking water sources (Tables 2–4). A
possible explanation for findings concerning shortness of breath
in women relates to the presence of weakness. Women who
are feeling weak might be able to cope during the day without
needing to physically exert themselves sufficiently to report
feeling short of breath. This might not be true to the same
extent for men who mainly work in agriculture, although they
also had the highest prevalence of shortness of breath in the
mid-exposure category. Although the numbers were small,
there was evidence of respiratory effects in children, especially
in the age range 10–19.
The results in Table 6 indicate that in this population, the
presence of respiratory effects was largely confined to those
who had the arsenic-caused skin lesions. Why this should be so
is not clear, but could be related to some underlying suscepti-
bility to arsenic effects. In Chile, it was also noted that there
were differences in respiratory disease in schoolchildren with
skin lesions compared to those without the lesions.
3
Inter-
estingly, this was not true for reported weakness which while
dramatically increased in those with skin lesions (Table 6, POR
15.3 and 14.2 for females and males, respectively), was still
markedly elevated in those with high current exposures who
did not have skin lesions (age-adjusted POR of 6.7 and 5.4).
Weakness is a highly subjective symptom which has previously
been reported in arsenic-exposed patients.
10
The reason people
exposed to high arsenic levels report feeling weak is not clear.
While arsenic can cause peripheral neuropathy, it is not known
to cause central nervous system effects that could explain general
feelings of weakness.
Although information about the relationship between
ingested arsenic and non-malignant respiratory effects has so
far only been reported from Chile and now India, studies from
arsenic-affected regions in Taiwan, Chile and Argentina show
marked increases in lung cancer mortality.
1,4,5,18,19
It is of
interest to note that many established lung carcinogens, includ-
ing smoking, asbestos and silica, also cause non-malignant
respiratory disease. The surprising characteristic of arsenic is
that it seems to increase both malignant and non-malignant
respiratory disease following ingestion.
While toxicological mechanisms for pulmonary effects of
inorganic arsenic are not known, some reports have demon-
strated that arsenic can accumulate in human lung tissue thus
enhancing the plausibility that the metal can produce respiratory
effects. Figueroa et al. noted evidence of lung tissue accumu-
lation in humans.
20
They investigated mummies hundreds of
years old that were found in Region II of Chile, an area that has
had high arsenic levels in drinking water. Kidney, liver, nail,
and lung tissues had some of the highest concentrations of total
arsenic, followed by the skin, intestines, hair, ribs, and muscles,
respectively. Further, case reports from poisoning deaths have
also demonstrated that high levels of arsenic occur in the
lungs.
21,22
In the first case, the lung tissue concentration of
total arsenic at autopsy of a 3-year-old boy who accidentally
ingested a weed killer containing 44% sodium arsenite was
7550 µg/kg. In the second case, a 25-year-old white male
ingested 8 g of arsenic trioxide. At autopsy, the largest total
arsenic concentration was found in the gastrointestinal tract,
but a concentration of 2750 µg/kg was also discovered in the
lungs. An autopsy study determined that the mean lung tissue
arsenic concentration was sixfold greater in 85 copper smelter
workers in Sweden compared to 25 non-exposed controls
(35 versus 6 µg/kg wet weight).
14
ARSENIC AND RESPIRATORY EFFECTS 1051
Table 6 Age-adjusted prevalence odds ratios (POR) for respiratory effects in non-smokers comparing those exposed to >500 µg/l to participants
exposed to ,50 µg/l
Females Males
Cases exposed Cases exposed
to >500 µg/l POR (95% CI) to >500 µg/l POR (95% CI)
All participants
Cough 22 2.4 (1.4–4.1) 25 1.6 (1.0–2.7)
Crepitations and/or rhonchi 19 2.5 (1.4–4.4) 21 2.2 (1.3–4.1)
Shortness of breath 11 7.2 (2.8–18.5) 11 2.1 (0.9–4.4)
Weakness 47 7.2 (4.4–11.5) 20 6.9 (3.2–15.0)
With skin lesions
Cough 7 7.8 (3.1–19.5) 14 5.0 (2.6–9.9)
Crepitations and/or rhonchi 8 9.6 (4.0–22.9) 12 6.9 (3.1–15.0)
Shortness of breath 4 23.2 (5.8–92.8) 5 3.7 (1.3–10.6)
Weakness 10 15.3 (6.5–35.8) 8 14.2 (5.2–38.7)
Without skin lesions
Cough 15 1.8 (1.0–3.4) 11 0.9 (0.5–1.7)
Crepitations and/or rhonchi 11 1.6 (0.8–3.2) 9 1.2 (0.5–2.6)
Shortness of breath 7 5.2 (1.9–14.8) 6 1.5 (0.6–3.7)
Weakness 37 6.7 (4.1–11.1) 12 5.4 (2.3–12.8)
The main drawback of the current investigation is that
limited time existed for interviewing and carefully assessing
each subject involved in the large population survey that
included over 7000 participants. Observer bias was possible
during interviews and clinical examination of patients with skin
lesions. We are therefore planning a more detailed assessment
of selected participants with high exposure and skin lesions,
including focused interviewing, medical examination and
spirometric testing. Nonetheless, the strength of the current
findings in terms of trend with water concentration and the
very high POR, along with the plausibility of finding non-
malignant respiratory effects based on studies in Chile, suggest
that non-malignant respiratory effects may indeed result from
ingestion of inorganic arsenic.
Acknowledgements
The epidemiological survey was funded by the Rajiv Gandhi
National Drinking Water Mission, Ministry of Rural Develop-
ment, Government of India, research grants W-11046/2/4/
96-TM II (R&D). Support for analysis and preparation for
publication was received from the US Environmental Protection
Agency (STAR Program), and from research grants P30-ES01896
and P42-ES04705 from the National Institute of Environmental
Health Sciences, NIH. Its contents are solely the responsibility of
the authors and do not necessarily represent the official views
of the Rajiv Gandhi National Drinking Water Mission, the
NIEHS, the NIH, nor the US EPA. Additional support came from
the University of California Center for Occupational and
Environmental Health. The authors thank Ms Cynthia Luna for
assistance in the preparation of the manuscript.
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