BIOLOGICAL T R A C E ELEMENT R E S E A R C H 2, 41-55 (1980)
Epidemiological Associations Between Arsenic and Cancer in Argentina S. C. BESUSCHIO,* A . C. P E R E Z D E S A N Z O , AND M. CROCI
National Academy of Medicine, Department of Pathology Las Heras 3092, Buenos Aires 142.5, Argentina Received June 6, 1979; Accepted August 27, 1979
Abstract The population of a large central area of Argentina is affected by a syndrome designed as "regional and endemic chronic hydroarsenicism." A number of types of neoplasms, especially of skin, urinary bladder, and of digestive system, occur with higher frequency in these areas. Drinking water in some of the affected areas contains from 0.1 to 1.2 mg/L of As. Index Entries: Epidemiology, of arsenic and cancer in Argentina; arsenic, and cancer in Argentina; cancer, and arsenic in Argentina; Argentina, arsenic and cancer epidemiology in.
Introduction The scope of our study is to analyze all data on the relationship between cancer and arsenic that we were able to extract from the Republic of Argentina's General Registry of Pathology, an institution that gives assistance to those hospitals in the provinces that have no pathology department. These histopathological data are limited to but include the entire, area of HACRE (hidroarsenicismo cronico regional endemico) in which regional and endemic chronic hydroarsenicism occurs, according to Tello (1). It is a well known fact that the use of waters containing arsenic in a concentration exceeding the maximum compatible with potability can give rise to progressive skin and peripheral and cardiac circulatory disorders, as described originally by Ayerza (2) in relation to the affected region, and as 9 1980 by The Humana Press Inc. All rights of any nature whatsoever reserved. 0163~1984/80/03004)041 $03.00
41
42
BESUSCHIO ET AL.
also referred to in the preliminary report of Goyenechea, from Rosario City, who reported the first recognized case of the disease in the area (3). Our analysis was carried out in order to obtain relative frequency data on the different types of cancer found in the population that live in the area, which has an arsenic content in the water of 0.2-1.00 mg/L, and which can no longer be considered harmless (0.1 mg/L) (4). Biagini and Vazquez in the city of Cordoba (in the midwest of the province of Cordoba), have found high levels, from 0.12 to 1.20 mg/L, of arsenic in different samples of drinking water (5). Occasionally, we have seen in our country other environmental sources of high arsenical content; e.g., the components of sheep-dip (arising from the use of arsenite of soda for the treatment of mange in sheep) contaminating the water. One focus of the disease was described by Castano and Magalhaes (6) in the southest province of Santa Cruz. In other countries other sources of arsenicism are, or have been, the insecticides and fungicides used in wine production (Germany and France) and among the copper smelter workers (USA) (7).
Area of Study The region where high endemic concentrations of inorganic arsenic are frequently found in potable water covers the south, central, and east areas of the province of Crrdoba, and a small part of the borders of the provinces of Sante Fr, Chaco, San Luis, and La Pampa. The population of these areas fundamentally consists of groups of immigrants from Italy and other European countries, or their descendants; people with fair eyes and skin, factors that predispose them to suffer skin preneoplastic and neoplastic conditions, especially when they are also agrarian workers (8). These are predominantly agricultural and cattle raising regions, with meat and vegetables as the basic foods of the populace. Unfortunately, we do not know the age composition of the surveyed population of the endemic area since only the total provincial population data was available.
Hospitals and Cities of the Endemic Region Included in the Period of Study The list of the hospitals covering some cities of the area, and the number of cases included are given in Table I. The period of study covered the years 1949-1958 (Tome I--histopathological diagnosis #1 to Tome XL--histopathological diagnosis #28900 of the General Registry of Pathology). This study was made to obtain only, with the well known possible bias of the
43
ARSENIC AND CANCER IN ARGENTINA
TABLE 1 The Endemic Region Province
City
Cfrdoba
Rio Cuarto Bell Ville Marcos Jufirez San Francisco Venado Tuerto Villa Angela Villa Mercedes General Pico Int. Alvear
Santa F~ Chaco San Luis La Pampa
Hospitals
Cases
2 1 1 1 1 1 1 1 1
404 86 31 71 41 9 34 10 2
Total number of malignant tumors:
688
histopathological source of data, the relative frequencies of the different types of neoplasms.
Results The results of our study are summarized in Tables 2-12.
Discussion
Previous Reports From a review of experimental arsenical cancer studies, it can be concluded that arsenic along "has given only doubtful results" (9). The difficulties were caused by "the occurrence of spontaneous tumors in the animals, by the high toxicity of arsenic, which leads to an early death of the animals, and by the fact that arsenic has a very long latency period for the production of malignancy, usually surpassing that of the average life of the animals" (7). "The clinical and epidemiological studies have added evidence of causality for arsenic in skin lesions and neoplasms, but the effects of this carcinogen have not been readily detected in experimental animals until today (I0). Despite these earlier statements, there exist two interesting observations on the effects of selenium and arsenic on the genesis of spontaneous mammary tumors in inbred C3H mice by Schrauzer et al. (11, 12). The first (11) refers to the inhibition of the spontaneous tumors by arsenic, and more particularly by selenium, but arsenic caused a "significant enhancement of the growth rate of spontaneous or transplanted mammary tumors."
44
BESUSCHIO ET AL.
-~-I~I
I--I r-i
0
Z
~5
0
0
~J
,--1 o
Epidemiological Associations Between Arsenic and Cancer in Argentina S. C. BESUSCHIO,* A . C. P E R E Z D E S A N Z O , AND M. CROCI
National Academy of Medicine, Department of Pathology Las Heras 3092, Buenos Aires 142.5, Argentina Received June 6, 1979; Accepted August 27, 1979
Abstract The population of a large central area of Argentina is affected by a syndrome designed as "regional and endemic chronic hydroarsenicism." A number of types of neoplasms, especially of skin, urinary bladder, and of digestive system, occur with higher frequency in these areas. Drinking water in some of the affected areas contains from 0.1 to 1.2 mg/L of As. Index Entries: Epidemiology, of arsenic and cancer in Argentina; arsenic, and cancer in Argentina; cancer, and arsenic in Argentina; Argentina, arsenic and cancer epidemiology in.
Introduction The scope of our study is to analyze all data on the relationship between cancer and arsenic that we were able to extract from the Republic of Argentina's General Registry of Pathology, an institution that gives assistance to those hospitals in the provinces that have no pathology department. These histopathological data are limited to but include the entire, area of HACRE (hidroarsenicismo cronico regional endemico) in which regional and endemic chronic hydroarsenicism occurs, according to Tello (1). It is a well known fact that the use of waters containing arsenic in a concentration exceeding the maximum compatible with potability can give rise to progressive skin and peripheral and cardiac circulatory disorders, as described originally by Ayerza (2) in relation to the affected region, and as 9 1980 by The Humana Press Inc. All rights of any nature whatsoever reserved. 0163~1984/80/03004)041 $03.00
41
42
BESUSCHIO ET AL.
also referred to in the preliminary report of Goyenechea, from Rosario City, who reported the first recognized case of the disease in the area (3). Our analysis was carried out in order to obtain relative frequency data on the different types of cancer found in the population that live in the area, which has an arsenic content in the water of 0.2-1.00 mg/L, and which can no longer be considered harmless (0.1 mg/L) (4). Biagini and Vazquez in the city of Cordoba (in the midwest of the province of Cordoba), have found high levels, from 0.12 to 1.20 mg/L, of arsenic in different samples of drinking water (5). Occasionally, we have seen in our country other environmental sources of high arsenical content; e.g., the components of sheep-dip (arising from the use of arsenite of soda for the treatment of mange in sheep) contaminating the water. One focus of the disease was described by Castano and Magalhaes (6) in the southest province of Santa Cruz. In other countries other sources of arsenicism are, or have been, the insecticides and fungicides used in wine production (Germany and France) and among the copper smelter workers (USA) (7).
Area of Study The region where high endemic concentrations of inorganic arsenic are frequently found in potable water covers the south, central, and east areas of the province of Crrdoba, and a small part of the borders of the provinces of Sante Fr, Chaco, San Luis, and La Pampa. The population of these areas fundamentally consists of groups of immigrants from Italy and other European countries, or their descendants; people with fair eyes and skin, factors that predispose them to suffer skin preneoplastic and neoplastic conditions, especially when they are also agrarian workers (8). These are predominantly agricultural and cattle raising regions, with meat and vegetables as the basic foods of the populace. Unfortunately, we do not know the age composition of the surveyed population of the endemic area since only the total provincial population data was available.
Hospitals and Cities of the Endemic Region Included in the Period of Study The list of the hospitals covering some cities of the area, and the number of cases included are given in Table I. The period of study covered the years 1949-1958 (Tome I--histopathological diagnosis #1 to Tome XL--histopathological diagnosis #28900 of the General Registry of Pathology). This study was made to obtain only, with the well known possible bias of the
43
ARSENIC AND CANCER IN ARGENTINA
TABLE 1 The Endemic Region Province
City
Cfrdoba
Rio Cuarto Bell Ville Marcos Jufirez San Francisco Venado Tuerto Villa Angela Villa Mercedes General Pico Int. Alvear
Santa F~ Chaco San Luis La Pampa
Hospitals
Cases
2 1 1 1 1 1 1 1 1
404 86 31 71 41 9 34 10 2
Total number of malignant tumors:
688
histopathological source of data, the relative frequencies of the different types of neoplasms.
Results The results of our study are summarized in Tables 2-12.
Discussion
Previous Reports From a review of experimental arsenical cancer studies, it can be concluded that arsenic along "has given only doubtful results" (9). The difficulties were caused by "the occurrence of spontaneous tumors in the animals, by the high toxicity of arsenic, which leads to an early death of the animals, and by the fact that arsenic has a very long latency period for the production of malignancy, usually surpassing that of the average life of the animals" (7). "The clinical and epidemiological studies have added evidence of causality for arsenic in skin lesions and neoplasms, but the effects of this carcinogen have not been readily detected in experimental animals until today (I0). Despite these earlier statements, there exist two interesting observations on the effects of selenium and arsenic on the genesis of spontaneous mammary tumors in inbred C3H mice by Schrauzer et al. (11, 12). The first (11) refers to the inhibition of the spontaneous tumors by arsenic, and more particularly by selenium, but arsenic caused a "significant enhancement of the growth rate of spontaneous or transplanted mammary tumors."
44
BESUSCHIO ET AL.
-~-I~I
I--I r-i
0
Z
~5
0
0
~J
,--1 o
