Arsenic in Drinking Water (1999) / Chapter Skim
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4 Health Effects of Arsenic
4 Health Effects of Arsenic
Pages 83-149
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From page 83... ...
determined that inorganic arsenic compounds are skin and lung (via inhalation) carcinogens in humans.
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From page 84... ...
Most of them did not provide the informational quality necessary for interpretation of dose-response relationships. However, many of the studies included data that are valuable in establishing the level of risk of particular internal cancers associated with a range of likely arsenic exposures (see Table 4-1)
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From page 85... ...
. TABLE 4-1 Summary of Cancer End Points Available for Quantitative Risk Assessment of Cancer and Ingested Arsenic Exposures Cancer Site Study Skin Bladder Lung Kidney Nasal Liver Prostate Other Ecological studies Tseng et al.
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Mortality, 1989-1993; national rates for 1991 used as the standard for the SMR; arsenic concentration is population-weighted average for major cities or towns in Region II, 1950-1974; information in paper adequate to calculate increase in risk per unit exposure ( Table continued on next page )
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From page 87... ...
; SMR, standardized mortality ratio; COPD, chronic obstructive pulmonary disease
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From page 88... ...
estimates increase in age-adjusted mortality per 100,000 per increase in arsenic at 100 pg/L of water Rate: Wu et al. SW Average arsenic: Male Female Male Female Mortality, 1973-1986 in 42 villages 1989 Taiwan <0.30 ppm 9 4 8.42 3.42 in Taiwan 0.30-0.59 ppm 11 13 18.90 19.42 ³ 0.60 ppm 6 16 25.26 57.98 SMR: Hopenhayn Cordoba County group: Male Female Male Female SMRs using national age-specific Rich et al.
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From page 89... ...
; SMR, standardized mortality ratio.
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From page 90... ...
3.1(2.7-3.7) as the standard for the SMR; Chile below 100 µg/L after arsenic concentration is 1980 to 569 µg/L in 1955 population-weighted average 1959; by city and 5-yr for major cities and towns in period, range was 40-870 Region II, 1950-1974; µg/L information in paper adequate to calculate increase in risk per unit exposure ( Table continued on next page )
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From page 91... ...
, regression coefficient (standard error) ; SMR, standardized mortality ratio.
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From page 92... ...
; most wells had arsenic concentrations of 0.4-0.6 ppm. Prevalence of skin cancer, keratoses, and hyperpigmentation were calculated for villages in three exposure groups: 0.0-0.29 ppm, 0.30-0.59 ppm, and 0.60 ppm and over.
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From page 93... ...
(1989) provided quantitative information on arsenic concentrations in the drinking water of 42 villages in southwestern Taiwan and calculated age-adjusted cancer mortality during the period 1973-1986 within three groups of villages stratified by exposure concentration (less than 0.30 mg/L, 0.30-0.59 mg/L, and 0.60 mg/L or more)
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From page 94... ...
In the highest exposure group, comprising two counties, arsenic exposure data were presented in tabular form by town. Arsenic concentra
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Among women, the number of excess lung cancer deaths was 84 in the high exposure counties, which is 7 times more than the corresponding number of 12 for bladder cancer. Deaths from chronic obstructive pulmonary disease (COPD)
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From page 96... ...
and the Smith study in Chile (1998) is that they confirmed earlier observations from Taiwan of increased risk for bladder and lung cancers after exposure to inorganic arsenic in drinking water.
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1992 Kingdom Chiou et al. SW Taiwan Cumulative arsenic: Relative risk: Incidence among a cohort of 2,556 subjects 1995 <0.1 mg/L/yr 3 1.0 0.1-19.9 mg/L/yr 7 3.1 (0.8-12.2)
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From page 98... ...
; also, one death at age 963 mg 1 5.00 (2.0-15) 85 and mention of bladder cancer as 1,901 mg 1 (exposure ³ 500 mg)
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. For cumulative arsenic exposures of 0, 0.1-19.9, and 20 mg/L or more times the number of years, relative risks were as follows: bladder cancer, 1.0 (referent)
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Occupational Studies Inhaled inorganic arsenic is a recognized cause of lung cancer. That effect is pertinent to arsenic ingestion and lung cancer because it supports the biological plausibility of a causal relationship between ingested inorganic arsenic and lung cancer.
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From page 101... ...
Potential reproductive and developmental effects associated with chronic ingestion of arsenic are discussed in a later section. Cutaneous Effects In contrast to many of the early nonspecific multisystemic signs and symptoms of chronic arsenic poisoning that are challenging to diagnose, the classic cutaneous manifestations are distinctive and characteristic.
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Page 102 FIGURE 4-1 Photographs of West Bengal patients with arsenic-induced skin lesions. (A) Arsenic keratosis on plantar aspect of the feet. (B)
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. The magnitude of arsenic dose and the time frame of exposure necessary to induce the hyperpigmentation and hyperkeratoses characteristic of chronic arsenic intoxication have undergone limited investigation.
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Limited evidence indicates that hyperpigmentation and keratoses due to arsenic exposure might serve as markers of susceptibility for other outcomes, including skin cancers and internal cancers. A small study in England of
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Cutaneous signs of chronic arsenic poisoning are usually apparent. Liver-function tests are generally normal. Histopathological examination of the liver might find periportal fibrosis associated with slight-tomoderate enlargement of the portal tracts and mild or no inflammatory-cell infiltration. Obliterative intimal hypertrophy of intrahepatic venules have been reported which results in obstruction of portal venous flow, increased splenic
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From page 106... ...
Chronic ingestion of inorganic arsenic, most notably from drinking-water sources and arsenic-contaminated wine or wine substitutes, has been associated with the insidious development of peripheral vascular disease. The most prominent reports of arsenic-related peripheral vascular disease have originated from southwestern Taiwan, where the ingestion of arsenic-containing artesian well water from the early 1900s through the late 1950s to early 1960s was associated with the development of more than 1,000 cases of blackfoot disease.
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From page 107... ...
(1994) cited several German reports of overt peripheral vascular disease, including thromboangiitis obliterans and overt gangrene of the extremities, in German vintners with chronic arsenic poisoning from consumption of arseniccontaminated wine substitutes (Butzengeiger 1940, as cited in Engel et al.
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From page 108... ...
described a case study of 125 patients diagnosed with chronic arsenic poisoning as a result of occupational or environmental exposure to arsenic from smelter emissions contaminating the air, surface drinking water, and the residential environment of an arsenic mining and refining area in Toruku, Japan. The magnitude of exposure to arsenic and to other suspected pollutants, such as sulfur dioxide and other metals and particulates, was not quantified, but 93% of the subjects had melanosis, 92% had hyperkeratosis, and approximately 45 % had Bowen's disease.
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From page 109... ...
The exposed subjects, with a mean age of 60 years, consumed artesian well water with high arsenic content for at least 30 years ending 20-30 years ago. The presence of cutaneous signs of chronic arsenic poisoning and the magnitude of past or current arsenic exposure were not reported.
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From page 110... ...
. Because hypertension and vascular occlusion are risk factors for death from ischemic heart disease or other cardiovascular illnesses, several investigators have examined the association between arsenic exposure and cardiovascular mortality.
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from 1973 to 1986. A statistically increased trend was observed for increased mortality from peripheral vascular disease and cardiovascular disease with increasing median arsenic concentrations in well water in the decedent's community.
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From page 112... ...
, and 6.47 (CI = 1.8822.24) for subjects with a cumulative arsenic exposure of 0.1-9.9 mg/L-yr, 10.0-19.9 mg/L-yr, and 20.0 mg/L-yr or more, respectively, compared with those without arsenic exposure.
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From page 113... ...
Hematological Effects Acute and chronic arsenic poisoning might result in anemia, leukopenia, and thrombocytopenia. Effects on those cell lineages can be simultaneous and can appear within a week of high-dose acute arsenic poisoning.
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. The hematological consequences of subacute and chronic arsenic poisoning can appear similar to that resulting from acute arsenic poisoning.
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. The results suggest that arsenic-induced changes in erythrocyte membrane integrity and deformability could contribute to microvascular occlusion and related peripheral vascular effects of chronic arsenic exposure (see Cardiovascular Effects above)
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From page 116... ...
were not significantly correlated with either mean well-water arsenic concentration, daily arsenic consumption, or log urinary arsenic excretion. Pulmonary Effects The possible role of chronic arsenic ingestion in the genesis of nonmalignant pulmonary disease has been suggested in a few case series describing medical problems among individuals chronically exposed to increased concentrations of arsenic in drinking water.
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Arsenic concentrations from first-morning-void urine from the exposed and control groups yielded means of 758 µg/L and 37 µg/L, respectively. The peripheral blood lymphocyte
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Resistance to Western encephalitis virus increased when arsenic was administered at the time of viral inoculation (a possible direct antiviral effect of the arsenic) but decreased if arsenic exposure followed the inoculation by 1 day.
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. Neurological Effects Acute inorganic arsenic intoxication that produces initial gastrointestinal or cardiovascular symptoms can be followed by the delayed onset of central or peripheral nervous-system involvement.
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As noted and reviewed by Hotta (1989) , peripheral neuropathy has not been identified as a common or significant finding in the cohorts affected by chronic arsenical dermatitis from well water in southeastern Taiwan; Cordoba, Argentina; or Antofagasta, Chile.
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(1994) investigated the relationship between cumulative arsenic exposure from artesian well water and the prevalence of diabetes mellitus in 891 adults who were over 30 years of age and residing in the blackfoot-disease
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examined the relationship between diabetes mellitus and arsenic exposure in two occupational cohorts. In a nested case-control study of a history of diabetes mellitus among 116 deceased male residents of a northern Swedish parish who had been employed at a copper smelter, the Mantel-Haenszel age-adjusted odds ratio associated with job-related arsenic exposure was 3.3 (95% CI = 0.5-30)
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(1998) conducted a cross-sectional study in western Bangladesh of the prevalence of diabetes mellitus among residents who had hyperkeratosis attributed to consumption of tube well water containing increased concentrations of arsenic.
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Another series of evaluations of demographic data from 1970 to 1987 indicated that frequency of stillbirths and spontaneous abortions was increased in a population drinking from wells with arsenic concentrations exceeding 100 µg/L (Börzsönyi et al. 1992; Rudnai et al.
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From page 125... ...
The developmental toxicity of arsenite has also been evaluated in hamsters. Arsenite was more embryotoxic than arsenate: an intravenous injection of sodium arsenite at 10 mg/kg on gestation day 8 killed 90% of the embryos; at 20 mg/kg, sodium arsenate killed 44% (Willhite 1981)
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From page 126... ...
The fertility of adults appeared to be unaffected. Recently completed studies reported in abstract form describe the results of oral and inhalation developmental toxicity tests using arsenic trioxide in rats.
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From page 127... ...
Eye defects, exencephaly, renal agenesis, gonadal agenesis, and rib and vertebral abnormalities were the most commonly observed malformations. A Segment II study was conducted in rabbits using gavaged arsenic acid at doses of 0.19, 0.75, and 3.0 mg/kg per day on gestation days 6-18 (Nemec et al.
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In contrast to the rodents, the marmoset accumulated arsenic in the testis as well. Thus, there is reason to investigate the effects of arsenic exposure on male reproductive health.
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. Recent studies found that arsenic readily crosses the human placenta, giving rise to arsenic concentrations that are about as high in cord blood as in maternal blood (Concha et al.
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, the subcommittee believes that the evidence is now sufficient to include bladder and lung cancer among the cancers that can be caused by ingestion of inorganic arsenic. With minor exception, the epidemiological evidence for cancer comes from places where exposed populations were exposed to arsenic concentrations in drinking water of at least several hundred micrograms per liter.
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From page 131... ...
Recent studies from Mexico suggest that those low concentration rates can also perturb porphyrin metabolism; however, the impact of this disturbance on clinical function is not fully determined. Peripheral vascular disease has been associated with chronic arsenic ingestion in epidemiological studies conducted in populations exposed via drinking water in Taiwan.
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From page 132... ...
Recent studies in southwestern Taiwan and Bangladesh associated chronic arsenic ingestion in drinking water with an increased risk of diabetes mellitus. The study subjects were drawn from populations with overt cutaneous signs of arsenic intoxication; information is lacking on the magnitude of the potential risk associated with exposure to low concentrations of arsenic.
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From page 133... ...
Other studies of less critical importance but nonetheless needed to fill important data gaps include the following: —Detailed clinical studies and preliminary epidemiological studies to better characterize the effect of low-to-moderate chronic arsenic exposure (0.01 to 0.03 mg/kg per day) on immune function, porphyrin metabolism, and respiratory function.
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1978. Arsenic exposure and mortality: A case-referent study from a Swedish copper smelter.
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1987. Some Potential Problems in Assessing the Effects of Chronic Arsenic Exposure in North Mexico [preprint extended abstract]
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1979. Liver disease associated with chronic arsenic ingestion.
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1994. Vascular effects of chronic arsenic exposure: A review.
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1992. Chronic arsenic poisoning from well water in a mining area in Thailand.
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1993. Observations on the doseresponse curve for arsenic exposure and lung cancer.
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Clinical aspects of chronic arsenic poisoning due to environmental and occupational pollution in and around a small refining spot [in Japanese]
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1989. Cumulative arsenic exposure and lung cancer in smelter workers: A dose-response study.
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1983. The consequences of chronic arsenic poisoning among Moselle wine groweres.
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1980. Cases of bladder cancer caused by chronic arsenic poisoning [in Hungarian]
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Axelson. 1995. Diabetes mellitus and arsenic exposure: a second look at case-control data from a Swedish copper smelter. Occup.
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From page 145... ...
The sequelae of chronic arsenic poisoning in Moselle vintners.
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1998a. An inhalation developmental toxicity study of arsenic trioxide in rats.
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1989. Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China.
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1982. Arsenic exposure, smoking and respiratory cancer in copper smelter workers.
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1980. Mathematical model of mean age, mean arsenic dietary dose and age-specific prevalence rate from endemic chronic arsenic poisoning: A human toxicology study. Zentralbl.
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