Arsenic Exposure and Cognitive Performance in Mexican Schoolchildren

Abstract

Recent studies indicate that in several regions of the world, arsenic concentration in water is much higher than accepted levels (Smedley and Kinniburgh 2002). The concern with As contamination of drinking water is that consumption and use of this water in cooking can increase As exposure in humans (Del Razo et al. 2002). In Mexico, the amount of this contaminant in ground water varies from 10 to 5,000 μg/L (Del Razo et al. 1990). Del Razo et al. (1990; 1994) reported on the problem of As-contaminated groundwater in the Lagunera Region of northern Mexico, with > 50% of samples having As concentrations > 50 μg/L, which was the former level of reference set by the World Health Organization (International Programme on Chemical Safety 2001). The predominant type of As in 90% of the samples was pentavalent arsenic.

In 1977, the presence of As in potable water was reported in the city of Torreón, the main city in the Region Lagunera and the site of the most important metallurgic complex of Mexico. As concentration in Torreón’s water was up to 4–6 mg/L, far above the present 10-μg/L limit (Cebrian et al. 1994; Mandal and Suzuki 2002). Benin et al. (1999) evaluated heavy metal contamination of soil in three residential areas that surround the smelter and found that As levels had a median of 113 μg/g, and ranged from 78 to 287 μg/g. These levels exceeded the level at which the U.S. Environmental Protection Agency (EPA) designated cleanup goals for Superfund sites, 5–65 μg/g (U.S. EPA 1997).

Approximately 60–90% of the soluble inorganic arsenic (InAs) components are absorbed through the gastrointestinal tract (Hall 2002). In humans, InAs metabolism involves at least five metabolites that can exert toxic effects (Valenzuela et al. 2005). The measure of urinary As (UAs) excretion is a good biomarker for chronic exposure via drinking water [Agency for Toxic Substances and Disease Registry (ATSDR) 2000]. As concentration in urine, normally < 10 μg/L, can reach as high as 50 μg/L in adults and children living close to metal foundries (Carrizales et al. 2006; Polissar et al. 1990).

The negative consequences of As exposure in humans include respiratory, gastrointestinal, hematologic, hepatic, renal, dermic, neurologic, and immunologic effects (ASTDR 2000; Garcia-Vargas and Hernandez-Zavala 1996; International Programme on Chemical Safety 2001), many of which continue even after the contaminant source is controlled (Diaz-Barriga et al. 1997). As can also have detrimental effects on the central nervous system and cognitive development in children (International Programme on Chemical Safety 2001). Acute As exposure affects sensory nerves as well as the long axon neurons, which results in the clinical manifestation of numb extremities. Neurologic tests have shown nerve axonophathy and demyelination (Franzblau and Lilis 1989; Rodriguez et al. 2003; Yung 1984). As also affects the content of brain monoamines, and the concentrations of dopamine and serotonin in the hippocampus, hypothalamus, cerebral cortex, and the striatum (Itoh et al. 1990; Mejía et al. 1997; Rodríguez et al. 2003).

Few reports have suggested a detrimental effect of As exposure on cognitive development and function, including disturbed visual perception, problems with visuomotor integration, psychomotor speed, attention, speech, and memory. (Calderón et al. 2001; Rodriguez et al. 2003; Tsai et al. 2003). In this regard, the effects of As are similar to and could be confounded with the effects of other environmental contaminants such as lead. In fact, in many regions of the world, As exposure co-occurs with exposure to other contaminants such as lead (Carrizales et al. 2006; Diawara et al. 2006). Poorer performance on a range of cognitive tests has been reported in children with low to moderate lead exposure in Torreón (Kordas et al. 2004) and other settings (Canfield et al. 2003; De Burbure 2006; Lanphear et al. 2000).

In this study we identified demographic and nutritional factors that are associated with UAs concentration in school-age children. We also investigated the influence of As exposure on cognitive function in these children.

Methods

Results

Demographic and biochemical characteristics of subjects are shown in Table 1. The mean ± SD of UAs was 58.1 ± 33.2 μg/L; 52% of the children had UAs concentrations > 50 μg/L, and 10% had UAs concentrations > 100 μg/L. Mean PbB concentration was 11.5 ± 6.3 μg/dL, and 50.7% of children had PbB above 10 μg/dL. The percentages of children with Hb, ferritin, and zinc deficiency were 9.8, 11.7, and 27.7%, respectively.

The association of sociodemographic variables with UAs is shown in Table 2. A significant difference was found between boys and girls in all As compounds: UAs was 11.85 μg/L higher in boys than in girls (p < 0.01). UAs concentration was also associated with SES: UAs in the low SES group was significantly higher than in medium and high SES groups (p < 0.01). Children of parents who had a high school or college education excreted less UAs than children of those who had primary or no education (p < 0.01). Children’s age was also associated with UAs concentration; younger children (6 years of age) excreted more UAs and MMAs (p < 0.01) and more InAs and DMAs (p < 0.05) than older children (7–8 years of age). PbB correlated positively with UAs concentration (Pearson R = 0.158, p < 0.01) (Tables 2 & 3). Nutritional status indicators were not related to UAs concentrations (Table 3).

The overall unadjusted cognitive scores stratified by UAs concentration levels are shown in Table 4. Children in the group with high UAs concentration presented lower scores in 7 of 11 cognitive tests than children with low UAs concentration.

Table 5 shows the covariate-adjusted relationship between UAs concentration and cognitive performance. The analysis is also presented separately by sex and by UAs below and above 50 μg/L. Overall, a significant inverse association was found between UAs and the Visual–Spatial Abilities with Figure Design, the PPVT, the WISC-RM Digit Span subscale, and the Visual Search and Letter Sequencing Tests (p < 0.05). In the analysis stratified by UAs concentration, UAs was significantly associated with the PPVT, the WISC-RM Digit Span Subscale, the Sternberg Memory Test, and the Visual Memory Span at UAs levels ≤50 μg/L. In children with UAs > 50 μg/L, the Visual–Spatial Abilities with Figure Design, the Stimulus Discrimination, and Letter Sequencing Tests were significant at p < 0.05. For boys, the Visual–Spatial Abilities with Figure Design and the PPVT, Visual Search, and Letter Sequencing Tests had an inverse association with UAs (p < 0.05). And for girls, there was a significant negative association of UAs only with the WISC-RM Digit Span Subscale (p < 0.05). The significant associations of each metabolite with the cognitive function tests are also shown in Table 5 (type of arsenic in parentheses). In general, organic forms of As in urine affected more cognitive tests than did the inorganic forms.

Discussion

We found an association of UAs with several cognition tests such as Visual–Spatial Abilities with Figure Design, the PPVT, the WISC-RM Digit Span subscale, and the Visual Search and Letter Sequencing Tests. These associations were independent from sociodemographic variables, nutritional status, and PbB. When analysis was stratified by UAs, some tests were associated with UAs at concentrations < 50 μg/L. However, some tests were not associated with the high UAs group even though the association was significant in the low UAs group and in the total sample; this might be attributed to the power reduction and increased variability in the high UAs group compared with the variability in the low UAs group. Cognitive tests that showed association with UAs represent complex cognitive processes such as memory, problem solving, and attention. Previous studies had shown an adverse relationship between As exposure and IQ (Calderon et al. 1999) and neurobehavioral performance (Rodriguez et al. 2003). Results from our study confirm earlier findings by Calderón et al. (2001) and Tsai et al. (2003) relating As exposure to memory alterations. These associations occurring even in children without elevated As concentrations could be caused by several possible mechanisms. As crosses the blood–brain barrier and has a wide range of effects on the white matter in the brain (Osterberg and Kernohan 1934). Evidence also shows that arsenite inhibits the synthesis and liberation of acetylcholine in brain slices (Kobayashi et al. 1987), and increases the monoamine activity in rat nervous system (Mejía et al. 1997; Tripathi et al. 1997). The increase in one monoamine, 5-hydroxyindole-3 acetic acid, is potentially neurotoxic (Jones et al. 2005; Mejía et al. 1997). Whatever the mechanism, the present investigation shows that exposure to As is associated with deficits in cognitive performance among school-age children, even at low exposure levels, affecting complex cognitive processes such as memory and problem solving, which could potentially interfere with performance at school.

We found different associations between UAs and cognitive tests in boys and girls. Several cognitive tests were negatively associated with UAs only in boys, and the Digit Span subscale, an evaluation of memory, was significantly associated with UAs only in girls. InAs seemed to affect only boys in the Letter Sequencing Test. According to ANOVA to detect differences in cognitive performance between boys and girls (data not shown), differences in associations of cognitive tests with UAs between boys and girls did not seem to be related with differences in sex. Although it has also been reported by others (Chen et al. 2003; Kristiansen et al. 1997; Vahter et al. 2007), it is unclear why boys would excrete more UAs, which thereby affects their cognitive performance.

SES had an inverse association with UAs in our study. Ahmad et al. (2001) also found an inverse association between arsenicosis and SES and education level, probably due to the lack of access to As-free water. In other studies, As was also related to nutritional status of participants. Sikder et al. (2005) found that most of the arsenicosis patients in their study also suffered from malnutrition. Minamoto et al. (2005) reported that children living in households with As-contaminated tube well water had lower height for their age than children living in noncontaminated households. Similarly, Islam et al. (2004) found higher rates of underweight in individuals with arsenicosis than in controls, and concluded that poor nutritional status increased the complications of arsenicosis. In our study we did not find an association between UAs excretion and height, weight, and iron and other minerals’ concentration in serum. The lack of association was probably owing to the fact that our subjects were generally well nourished. Only 2% were stunted and 10% were anemic; and the rate of children with high concentration of UAs was the same among anemic and nonanemic children.

In conclusion, our study of a population of children living in an area contaminated with both As and lead showed that As contamination affected children’s cognitive function independent of any effect of lead, even in children with UAs below the safe declared concentration limit of 50 μg/L (ATSDR 2000).

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