Prenatal exposure to phthalates is associated with decreased anogenital distance and penile size in male newborns.

Reproductive effects from phthalate exposure have been documented mostly in animal studies. This study explored the association between prenatal exposure to phthalate metabolites, anogenital distance and penile measurements in male newborns in Toluca, State of Mexico. A total of 174 pregnant women provided urine samples for phthalate analysis during their last prenatal visit, and the 73 who gave birth to male infants were included in the study. The 73 male newborns were weighed and measured using standardized methods after delivery. After adjusting for creatinine and supine length at birth, significant inverse associations were observed between an index of prenatal exposure to total phthalate exposure and the distance from the anus to anterior base of the penis (ß = -0.191 mm per 1 µg/l, P = 0.037), penile width (ß = -0.0414, P = 0.050) and stretched length (ß = -0.2137, P = 0.034); prenatal exposure to mono-2-ethylhexyl phthalate exposure was associated with a reduction in the stretched length of the penis (ß = -0.2604, P = 0.050). Human exposure to phthalates is a public health concern, and the system most vulnerable to its potential effects seems to be the immature male reproductive tract.

Parental occupational exposure to organic solvents and anencephaly in Mexico.

OBJECTIVE: To assess the relationship between parental occupational exposure to organic solvents, and the risk of anencephaly in Mexico. METHODS: A case-control study was conducted based on the registers of the Epidemiological Surveillance System for Neural Tube Defects in Mexico; 151 cases of anencephaly of > or =20 weeks' gestation were included. A control, born alive and without any apparent congenital malformations at birth, was selected for each case in the same maternity service in which the case was born. Information on occupational exposures, lifestyle habits, reproductive history, use of medicines, supplementation with multivitamins and folic acid, was obtained by a general questionnaire; a food frequency questionnaire was also applied to obtain information of daily intake of folate and other B vitamins. Occupational exposure to organic solvents was based on job title as a proxy for exposure and analysed considering two critical periods around conception. RESULTS: In logistic regression analysis, the odds of having a child with anencephaly was higher if the mother or the father was occupationally exposed to organic solvents during the periconceptional period, or when both parents or at least one of them were occupationally exposed during this period with an adjusted odds ratio of 2.97 (95% CI 1.36 to 6.52). CONCLUSIONS: The results support the hypothesis that both maternal and paternal occupational exposure to organic solvents can increase the probability of having a child with anencephaly.

PON1Q192R genetic polymorphism modifies organophosphorous pesticide effects on semen quality and DNA integrity in agricultural workers from southern Mexico.

Pesticide exposure, including organophosphorous (OP) insecticides, has been associated with poor semen quality, and paraoxonase (PON1), an enzyme involved in OP deactivation, may have a role on their susceptibility, due to PON1 polymorphisms. Our objective was to evaluate the role of PON1Q192R polymorphism on the susceptibility to OP toxicity on semen quality and DNA integrity in agricultural workers. A cross-sectional study was conducted in farmers with Mayan ascendancy from southeastern Mexico chronically exposed to pesticides; mostly OP. Fifty four agricultural workers (18-55 years old) were included, who provided semen and blood samples. Semen quality was evaluated according to WHO, sperm DNA damage by in situ-nick translation (NT-positive cells), PON1Q192R polymorphism by real-time PCR and serum PON1 activity by using phenylacetate and paraoxon. Two OP exposure indexes were created: at the month of sampling and during 3 months before sampling, representing the exposure to spermatids-spermatozoa and to cells at one spermatogenic cycle, respectively. PON1 192R and 192Q allele frequencies were 0.54 and 0.46, respectively. Significant associations were found between OP exposure at the month of sampling and NT-positive cells and sperm viability in homozygote 192RR subjects, and dose-effect relationships were observed between OP exposure during 3 months before sampling and sperm quality parameters and NT-positive cells in homozygote 192RR farmers. This suggests that cells at all stages of spermatogenesis are target of OP, and that there exists an interaction between OP exposure and PON1Q192R polymorphism on these effects; farmers featuring the 192RR genotype were more susceptible to develop reproductive toxic effects by OP exposure.

Maternal and paternal occupational exposure to agricultural work and the risk of anencephaly.

AIMS: To evaluate the association between parental occupational exposure to agricultural work and the risk of anencephaly in three Mexican states. METHODS: A paired case control study (1:1) was done based on records of the Epidemiological Surveillance System of Neural Tube Defects in Mexico; 151 cases of anencephaly of more than 20 weeks' gestation were selected between March 2000 and February 2001. Controls were selected from the same maternity services as those of the cases and were born alive without congenital malformations. Information was obtained from both parents by means of a general questionnaire, a food frequency questionnaire, and a specific questionnaire on occupational exposure to pesticides. Exposures were analysed with emphasis on the three months before and one month after the last menstruation periods (acute risk period (ARP)), as well as exposure prior to the above mentioned period (non-acute risk period (NARP)). RESULTS: The children of mothers who worked in agriculture in the ARP had a greater risk of anencephaly (OR = 4.57, 95% CI 1.05 to 19.96). The risk of fathers having a child with anencephaly was greater in those who applied pesticides irrespective of whether it was done in the ARP or the NARP (OR = 2.50, 95% CI 0.73 to 8.64; and OR = 2.03, 95% CI 0.58 to 7.08, respectively). CONCLUSIONS: These results support the hypothesis of the effect of maternal exposure to agricultural work on anencephaly and suggest that exposure of the father to pesticides in the periconceptional period or prior to this can also increase the risk of having an anencephalic child.

Organophosphorous pesticide exposure increases the frequency of sperm sex null aneuploidy.

It has been estimated that 4 of 1,000 live births and 35% of spontaneous abortions are aneuploid and that an important proportion of embryo and newborn aneuploidy is of paternal origin. Exposure to organophosphorous pesticides (OP) has been associated with sperm hyperploidy/polyploidy. Therefore, we aimed to assess the frequency of sperm aneuploidy (X, Y, and 18) and its relationship with urinary OP metabolites in agricultural workers. We performed multicolor fluorescence in situ hybridization on samples from nine men obtained before and during the pesticide spraying season to assess sperm aneuploidy. We measured urinary OP metabolite levels by gas-liquid chromatography. Aneuploidies were found in 0.67% of total sperm nuclei. The most frequent aneuploidy was the lack of a sexual chromosome or sex null (0.19%), followed by XY18 (0.15%) and XY18-18 (0.06%). OP metabolites detected at higher concentrations were dimethylthiophosphate, dimethyldithiophosphate, and diethylphosphate (DEP). There were no differences in average aneuploidy frequency or urinary metabolite levels between samples collected before and after exposure. However, Poisson regression analysis adjusted for age, alcohol intake, and sperm concentration showed significant associations between OP metabolite concentrations and increased frequency of sperm aneuploidies. The association was more evident between DEP and sex null, and the risk increased further during the spraying season. Thus, OP exposure could interfere with sperm chromosome segregation and increase the risk for genetic syndromes, such as Turner's. Further studies are required to assess the prevalence of spontaneous abortions, birth defects, and genetic syndromes in agricultural communities.

Assessing the health benefits of urban air pollution reductions associated with climate change mitigation (2000-2020): Santiago, São Paulo, México City, and New York City.

To investigate the potential local health benefits of adopting greenhouse gas (GHG) mitigation policies, we develop scenarios of GHG mitigation for México City, México; Santiago, Chile; São Paulo, Brazil; and New York, New York, USA using air pollution health impact factors appropriate to each city. We estimate that the adoption of readily available technologies to lessen fossil fuel emissions over the next two decades in these four cities alone will reduce particulate matter and ozone and avoid approximately 64,000 (95% confidence interval [CI] 18,000-116,000) premature deaths (including infant deaths), 65,000 (95% CI 22,000-108,000) chronic bronchitis cases, and 46 million (95% CI 35-58 million) person-days of work loss or other restricted activity. These findings illustrate that GHG mitigation can provide considerable local air pollution-related public health benefits to countries that choose to abate GHG emissions by reducing fossil fuel combustion.

Lead exposure in children living in a smelter community in region Lagunera, Mexico.

Industrial growth has created the potential for environmental problems in Mexico, since attention to environmental controls and urban planning has lagged behind the pace of industrialization. The aim of this cross-sectional study was to assess lead exposure in children aged 6-9 yr attending 3 primary schools and living in the vicinity of the largest smelter complex in Mexico. One of the schools is located 650 m distant from a smelter complex that includes a lead smelter (close school); the second is located 1750 m away from the complex and at the side of a heavy traffic road (intermediate school) in Torreon, Coahuila. The third school is located in Comez Palacio, Durango, 8100 m away from the smelter complex and distant from heavy vehicular traffic or industrial areas (remote school). Lead was measured in air, soil, dust, and well water. Lead in blood (PbB) was determined in 394 children attending the above mentioned schools. Determinations were performed by atomic absorption spectrometry. Diet, socioeconomic status, hygienic habits, and other variables were assessed by questionnaire. Median (range) PbB values were 7.8 microg/dl (3.54-29.61) in the remote school, 21.8 microg/dl (8.37-52.08) in the intermediate school and 27.6 microg/dl (7.37-58.53) in children attending the close school. The percentage of children with PbB > 15 microg/dl was 6.80%, 84.9%, and 92.1% respectively. In this order, the geometric means (range) of Pb concentrations in air were 2.5 microg/m3 (1.1-7.5), 5.8 microg/m3 (4.3-8.5), and 6.1 microg/m3 (1.6-14.9). The Pb concentrations in dust from playgrounds areas in the intermediate and close school settings ranged from 1,457 to 4,162.5 mg/kg. Pb concentrations in drinking water were less than 5 microg/L. Soil and dust ingestion and inhalation appear to be the main routes of exposure. Our results indicate that environmental contamination has resulted in an increased body burden of Pb, suggesting that children living in the vicinity of the smelter complex are at high risk for adverse effects of lead.

Exposure to arsenic and lead and neuropsychological development in Mexican children.

This cross-sectional study examined the effects of chronic exposure to lead (Pb), arsenic (AS) and undernutrition on the neuropsychological development of children. Two populations chronically exposed to either high (41 children) or low (39 children) levels of As and Pb were analyzed using the Wechsler Intelligence Scale for Children, Revised Version, for México (WISC-RM). Geometric means of urinary arsenic (AsU) and lead in blood (PbB) were 62.9+/-0.03 (microgAs/g creatinine) and 8.9+/-0.03 (microg/dl) for the exposed group and 40.2+/-0.03 (microgAs/g creatinine) and 9.7+/-0.02 (microg/dl) for the reference group. The height for age index (HAI) was used as an indicator of chronic malnutrition and sociodemographic information was obtained with a questionnaire. Lead and arsenic were measured by atomic absorption spectrophotometry. Data on full, verbal, and performance intelligence quotients (IQ) scores, long-term memory, linguistic abstraction, attention span, and visuospatial organization were obtained through the WISC-RM. After controlling for significant potential confounders verbal IQ (P<0.01) decreased with increasing concentrations of AsU. The HAI correlated positively with full-scale and performance IQ (P<0.01). Higher levels of AsU were significantly related to poorer performance on WISC-RM factors examining long-term memory and linguistic abstraction, while lower scores in WISC-RM factors measuring attention were obtained at increasing values of PbB. Our results suggest that exposure to As and chronic malnutrition could have an influence on verbal abilities and long-term memory, while Pb exposure could affect the attention process even at low levels.

[Acute effects of air pollution on health: evidence from epidemiological studies]. / Los efectos agudos de la contaminación del aire en la salud de la población: evidencias de estudios epidemiológicos.

OBJECTIVE: To summarize the evidence of acute health effects from exposure to particulate matter and ozone. MATERIAL AND METHODS: A meta-analysis was performed using random effect models, to summarize the health effects of pollution, published in major international and Mexican journals up to June 2000. RESULTS: Results were given as percent increase in ten units of PM10 (microgram/m3) and ozone (ppb). PM10 was found to have an effect on mortality (0.96%), hospital admissions (1.39%), emergency room visits (3.11%), respiratory symptoms (7.72%), pulmonary forced vital capacity (1.42%), and restricted activity days (7.74%). Ozone effects were equally significant. CONCLUSIONS: These findings show the great impact that air pollutants may have on the health of populations living in large metropolis.

Predictors of death from pulmonary tuberculosis: the case of Veracruz, Mexico.

OBJECTIVES: To identify factors (particularly social, economic and cultural), associated with the risk of death from pulmonary tuberculosis in Mexico. METHODS: A case-control study of patients receiving medical attention from the official health services of Veracruz, Mexico. Cases were deaths from pulmonary tuberculosis in 1993. Controls were survivors randomly selected from the State Tuberculosis Case Registry. Next of kin provided information for both cases and controls. RESULTS: Multivariate analysis of 161 cases and 161 controls showed an increased risk of dying for those patients who withdrew from treatment (odds ratio [OR] = 3.52), who were refused medical attention during some period of time in any health center (OR = 4.45), and who had a concomitant disease at the time of diagnosis (OR = 2.62). A linear trend with age was observed (OR = 1.02 per year), as well as a lower risk for those patients who were compliant with treatment and optimistic about surviving the disease (OR = 0.17). The risk of death was not associated with the presence of a health care unit in the town, time spent to get to the health center, or the residence of a patient in an urban area. CONCLUSIONS: These findings indicate that deaths due to tuberculosis in this area are not related to the geographical distribution of health services but to delays in treatment after the onset of disease and to the low adherence of patients to the treatment regimen.

Blood lead levels measured prospectively and risk of spontaneous abortion.

Studies of low to moderate level lead exposures have reported mixed findings regarding the risk of spontaneous abortion, despite lead's abortifacient properties at very high doses. To evaluate the risk of spontaneous abortion from low or moderate lead exposures, a nested case-control study was conducted within a cohort of pregnant women in Mexico City, 1994-1996. During their first trimester, 668 women enrolled, were interviewed, and contributed blood specimens. Pregnancies were followed by home visits or telephone calls. Spontaneous abortions before week 21 (n = 35) were matched with pregnancies that survived beyond week 20 (n = 60) on maternal age, hospital, date of enrollment, and gestational age at enrollment. Mean blood lead levels were 12.03 microg/dL for cases and 10.09 microg/dL for controls (p = 0.02). Odds ratios for spontaneous abortion comparing 5-9, 10-14, and > or =15 microg/dL with the referent category of <5 microg/dL of blood lead were 2.3, 5.4, and 12.2, respectively, demonstrating a significant trend (p = 0.03). After multivariate adjustment, the odds ratio for spontaneous abortion was 1.8 (95% confidence interval = 1.1, 3.1) for every 5 microg/dL increase in blood lead. Low to moderate lead exposures may increase the risk for spontaneous abortion at exposures comparable to US general population levels during the 1970s and to many populations worldwide today; these are far lower than exposures encountered in some occupations.

Air pollution and infant mortality in Mexico City.

Historic air pollution episodes of the 1950s led to acute increases in infant mortality, and some recent epidemiologic studies suggest that infant or child mortality may still result from air pollution at current levels. To investigate the evidence for such an association, we conducted a time-series study of infant mortality in the southwestern part of Mexico City in the years 1993 to 1995 using mortality data from death registrations and air pollution measurements from a monitoring station we operated. Excess infant mortality was associated with the level of fine particles in the days before death, with the strongest association observed for the average concentration of fine particles during the period 3 to 5 days previously: a 10-microg m(-3) increase in the mean level of fine particles during these 3 days was associated with a 6.9% excess of infant deaths (95% confidence interval 2.5-11.3%). Infant mortality was also associated with the levels of nitrogen dioxide and ozone 3 to 5 days before death, but not as consistently as with particles.

PIP: Air pollution episodes in London during the 1950s led to acute increases in infant mortality. Some recent epidemiologic study results suggest that infant and/or child mortality may still result from air pollution at current levels. Findings are presented from an investigation of the evidence for such an association in the southwestern part of Mexico City during 1993-95, using mortality data from death registrations and air pollution measurements from a monitoring station. There were 2798 infant deaths during the study period, or 3 per average day. Excess infant mortality was associated with the level of fine particles during the days before death, with the strongest association observed for the average concentration of fine particles during the 3-5 preceding days. A 10 mcg/cu. m increase in the mean level of fine particles during those 3-5 days was associated with a 6.9% excess of infant deaths. Infant mortality was also associated with the levels of nitrogen dioxide and ozone 3-5 days before death, but not as consistently as with particles.

[Difficulties of the methods for studying environmental exposure and neural tube defects]. / Dificultades en los métodos de estudio de exposiciones ambientales y defectos del tubo neural.

OBJECTIVE: To discuss the attitudes in the assessment of environmental exposures as risk factors associated with neural tube defects, and to present the main risk factors studied to date. RESULTS: Environmental exposures have been suggested to have a roll in the genesis of birth defects. However, studies conducted in human populations have found difficulties in the design and conduction to show such an association for neural tube defects (anencephaly, espina bifida and encephalocele) because of problems raised from: a) the frequency measures used to compare time trends and communities, b) the classification of heterogeneous malformations, c) the inclusion of maternal, paternal and fetal factors as an integrated process and, d) the assessment of environmental exposures. CONCLUSIONS: Hypothetically both maternal and paternal environmental exposures can produce damage before and after conception by direct action on the embryo and the fetus-placenta complex. Therefore, in the assessment of environmental exposures we need to take into account: a) both paternal and maternal exposures; b) the critical exposure period, three months before conception for paternal exposures and one month around the conceptional period for maternal exposures; c) quantitatively evaluate environmental exposures when possible, avoiding a dichotomous classification; d) the use of biological markers of exposure is highly recommended as well as markers of genetic susceptibility.

Mortality and ambient fine particles in southwest Mexico City, 1993-1995.

++Epidemiologic studies have focused attention on the health effects of fine particulate air pollutants <2.5 microm in diameter (PM2.5). To further characterize the potential effects of fine particles, we investigated the relationship of air pollution to mortality in Mexico City during 1993-1995. The concentration of PM2.5 was measured on a 24-hr integrated basis; concentrations of NO2 and ozone were measured hourly and reduced to 24-hr means. Daily mortality was determined from death registration records, and Poisson regression was used to model daily death counts as a function of air pollutant levels on the same and previous days, while controlling for temperature and periodic cycles. Without taking other air pollutants into account, a 10 microg/m3 increase in the level of PM2.5 was associated with a 1.4% increase in total mortality, both on the current day and 4 days after exposure [95% confidence interval (CI), 0.2-2.5]. An equivalent increase in PM2.5 was also associated with somewhat larger excesses of deaths among people over 65 years of age and from cardiovascular and respiratory causes, which occurred after a lag of 4 days. The mean concentration of ozone over a 2-day period was associated with a 1.8% increase in mortality from cardiovascular diseases. NO2 was not consistently related to mortality. Fine particles had an independent effect on mortality when modeled simultaneously with other pollutants, and the association of ozone with cardiovascular mortality was strengthened after adjusting for NO2 and PM2.5. These results support previous findings that urban air pollution at current levels leads to excess mortality and suggest that fine particles may play a causal role in producing that excess.

Particulate air pollution and daily mortality: can results be generalized to Latin American countries?

OBJECTIVE: Recently, a series of reports, based on ecological analyses of routinely collected data, have shown positive associations between measures of particle concentration and daily mortality counts in various cities of the US and Europe. MATERIAL AND METHODS: We reviewed the process of generalization of these results to Latin American countries addressing possible differences in air pollution mixtures, exposure profiles, and population susceptibility. RESULTS: A limitation to the process of generalization is the lack of a well-established biological mechanism by which particles may act on daily mortality. Also, sources and levels of ambient air pollution as well as population characteristics and habits vary widely between Northern communities of Europe and the US, and Latin American countries, which impairs the process of generalization. However, results of studies conducted in Latin American countries suggest a similar effect to that observed in Northern countries of Europe and the US. CONCLUSIONS: Despite uncertainty about the mechanism, there is sufficient evidence that particles are harmful for health. Control measures of particle emission are urgently needed in Latin American countries. Given the potential of misclassification of exposure, the dose-response relationship observed in Northern Europe and the US may not be adequate for Latin American populations. There is a need for a new generation of epidemiological studies including a specific assessment of exposure to fine particles and of events surrounding death.

Ozone, suspended particulates, and daily mortality in Mexico City.

To investigate acute, irreversible effects of exposure to ozone and other air pollutants, the authors examined daily death counts in relation to air pollution levels in Mexico City during 1990-1992. When considered singly in Poisson regression models accounting for periodic effects, the rate ratio for total mortality associated with a 100-ppb increment in 1-hour maximum ozone concentration was 1.024 (95% confidence interval (CI) 1.011-1.039). Measures of average ozone concentration were somewhat more strongly related to mortality. The rate ratio was 1.024 (95% CI 0.984-1.062) per 100 ppb for sulfur dioxide and 1.050 (95% CI 1.030-1.067) per 100 micrograms/m3 for total suspended particulates. However, when all three pollutants were considered simultaneously, only total suspended particulates remained associated with mortality, indicating excess mortality of 6% per 100 micrograms/m3 (rate ratio = 1.058, 95% CI 1.033-1.083), consistent with observations in other cities in the United States and Europe. The authors found no independent effect of ozone, but it is difficult to attribute observed effects to a single pollutant in light of the complexity and variability of the mixture to which people are exposed. Nevertheless, particulate matter may be a useful indicator of the risk associated with ambient air pollution.

Exposure assessment for workers applying DDT to control malaria in Veracruz, Mexico.

DDT has systematically been used in sanitation campaigns against malaria in Mexico. To assess chronic occupational exposure, we studied a group of workers dedicated to spraying houses to control malaria vectors in the state of Veracruz. Exposure was directly estimated for a subgroup of 40 workers by measuring DDT metabolites in adipose tissue samples and indirectly estimated for 331 workers by using a questionnaire to determine their occupational history. Participants ranged in age from 20 to 70 years, and 80% of the workers had been employed in the sanitation campaign for at least 20 years. The mean concentrations of extractable lipids found in adipose tissue samples were as follows: total DDT, 104.48 micrograms/g; p,p'-DDE, 60.98 micrograms/g; p,p'-DDT, 31.0 micrograms/g; o,p'-DDT, 2.10 micrograms/g; and p,p'-DDD, 0.95 microgram/g. The DDT metabolite p,p'-DDE was selected as the indicator of chronic exposure. An index of chronic occupational exposure was constructed according to worker position and based on the historical duration and intensity of DDT application. A linear model including this index, the use of protective gear, and recent weight loss explained 55% of the variation of p,p'-DDE concentrations in adipose tissue. By this model, the predicted values of p,p'-DDE concentration in adipose tissue for the 331 workers are between 9.56 micrograms/g and 298.4 micrograms/g of fat, with a geometric mean of 67.41 micrograms/g. These high levels of DDT in adipose tissue call for exposure prevention programs and the promotion of more secure application measures and hygiene. We also discuss the use of indirect measures of DDT exposure in epidemiological studies of health effects.