Inflammatory and cardiometabolic risk on obesity: role of environmental xenoestrogens.

CONTEXT: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. OBJECTIVE: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND PARTICIPANTS: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m(2)) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. RESULTS: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. CONCLUSIONS: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women.

Maternal and cord blood levels of aldrin and dieldrin in Delhi population.

Aldrin and dieldrin, structurally similar organochlorine pesticides belong to cyclodiene family and were widely used for agriculture and public health program in India. Although the manufacturing, use and import of aldrin and dieldrin have been banned in India since 2003, these pesticides are still persistent in environment and may be associated with adverse neurological and reproductive effects. The aim of this study is to assess the recent exposure level of aldrin and dieldrin and their placental transfer to fetus in normal healthy full-term pregnant women belonging to north Indian population undergoing normal delivery at Obstetrics and Gynecology department of UCMS and GTB hospital, Delhi. Quantitative analysis of aldrin and dieldrin residues in maternal and cord blood samples were carried out by gas chromatography system equipped with electron capture detector. The results of our study clearly revealed that maternal and cord blood levels of aldrin and dieldrin of pregnant women are age and dietary habit dependent. The aldrin level in maternal blood and dieldrin level in cord blood are higher in women in the age group 25-30 years than in women in age group of 19-24 years. Similarly, aldrin level in maternal blood is significantly higher in women with non-vegetarian dietary habit than in women with vegetarian dietary habit. No significant association is found for maternal and cord blood level. The results of the present study clearly demonstrate prenatal uptake of aldrin and dieldrin and provide recent information on the subsequent transplacental transfer.

Empirical and parametric likelihood interval estimation for populations with many zero values: application for assessing environmental chemical concentrations and reproductive health.

BACKGROUND: Understanding the health effects associated with environmental chemicals is challenging when individuals have concentrations at or below the laboratory limits of detection as well as when the values may round to zero or are presented in the form of 0 to substitute for missing values, which may result in many zeros in the database. Comparison of mean concentrations between individuals with and without disease necessitates estimation procedures that allow for data with many zero values. The main aim of this article is to propose and examine parametric and distribution-free methods for comparing data sets containing many zero observations. An important application of this approach is related to assessing environmental chemical concentrations and reproductive health. METHODS: We extended the empirical likelihood technique for estimating confidence intervals (CIs) in data sets with many zeros. We examined the proposed empirical likelihood interval estimations via a broad Monte Carlo study that compares the proposed method with parametric techniques. Certain characteristics of Monte Carlo simulations were chosen to be close to parameters of the real data set. We applied the method to a cohort study comprising 84 women aged 18-40 years who had undergone laparoscopy between 1999 and 2000 in whom serum concentrations of 2 organochlorine pesticides--Aldrin and beta-Benzene hexachloride (ß-BHC) were measured using gas chromatography with electron capture. RESULTS: When applied to the cohort study, the method produced efficient 95% CIs, allowing for the comparison of mean serum Aldrin concentrations for women with and without endometriosis (0.000338, 0.003561) and (0.000803, 0.004211), respectively. Mean ß-BHC concentrations also could be compared (0.000493, 0.005869) and (0.000680, 0.003807) based on individuals with and without the disease, respectively. Differences in mean concentrations for Aldrin and ß-BHC could be estimated (-0.001563, 0.003025) and (-0.003522, 0.002890), respectively. CONCLUSIONS: We found the empirical likelihood method for estimating CIs robust when data sets contain many zeros. In so doing, mean concentrations of Aldrin or ß-BHC did not differ by endometriosis diagnosis.

Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up.

OBJECTIVE: Dieldrin and aldrin, pesticides widely used until the 1970s, have been under suspicion of being carcinogenic. In this study, overall and cause-specific mortality was assessed in a cohort of 570 employees occupationally exposed to the pesticides dieldrin and aldrin to investigate the long-term health effects, in particular carcinogenic effects. METHODS: All of the employees worked in the production plants between January 1954 and January 1970 and were followed for cause-specific mortality until 30 April 2006. Based on dieldrin levels in blood samples taken from 343 workers during the exposure period, the total intake of dieldrin was estimated for each individual subjects in the cohort. The estimated total intake ranged from 11 to 7,755 mg of dieldrin, with an average of 737 mg. RESULTS: Two hundred and twenty-six workers had died before 30 April 2006 compared with an expected number of 327.3, giving a standardized mortality ratio (SMR) of 69.0 (95% confidence interval (CI): 60.3-78.7). Overall cancer mortality was also significantly lower than expected (SMR: 76.4, 95% CI: 60.8-94.9). Also, none of the specific cancer sites showed a significant excess mortality and no association between exposure level and cancer mortality was found. CONCLUSION: The results from this study support findings from other epidemiological and recent animal studies concluding that dieldrin and aldrin are not likely human carcinogens.

Serum levels of insulin-like growth factor-I in relation to organochlorine pesticides exposure.

CONTEXT: Insulin-like growth factor 1 (IGF-I) and organochlorine pesticides (OCs) have been involved in the pathogenesis of several diseases like cancer, diabetes and growth disorders. OBJECTIVE AND DESIGN: The potential relationship between the serum levels of various OCs and serum IGF-I was investigated in adults (176 men and 247 women) from a representative sample of the general population of the Canary Islands (Spain). RESULTS: After adjustment for potential confounders, which include body mass index, age, and IGF-binding protein-3 (IGFBP-3), IGF-I levels were significantly lower in the 247 women who showed detectable levels of p,p'-DDD (a DDT-metabolite) than in women who presented non-detectable levels of this pesticide (p=0.030), specially in 36-50 years old women. A similar negative relationship was also found between IGF-I and aldrin (a non-DDT-derivative) in women (p=0.049). In the group of 176 men, aldrin seemed to exert a similar negative effect on IGF-I (p=0.046) and this effect was clearly significant in the oldest group (51-65 years) (p=0.009). A non-linear dose-response curve was observed between Total Cyclodienes Body Burden (Total Cyclodienes; sum of aldrin, dieldrin and endrin) and IGF-I in men (p=0.024). These findings suggest that OCs could modulate the IGF-system in a way that is highly influenced by gender, age and by chemical or combination of chemicals implicated. Such circumstances may contribute to the development of a number of diseases related to IGF-I and should be taken into account in public health decisions.

Quantification of low levels of organochlorine pesticides using small volumes (

A solid phase extraction and gas chromatography with negative chemical ionization mass spectrometry in scan mode (GC-NCI-MS) method was developed to identify and quantify for the first time low levels of organochlorine pesticides (OCs) in plasma samples of less than 100 microl from wild birds. The method detection limits ranged from 0.012 to 0.102 pg/microl and the method reporting limit from 0.036 to 0.307 pg/microl for alpha, gamma, beta and delta-hexachlorocyclohexane (HCH), heptachlor, aldrin, heptachlor epoxide, endosulfan I, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), dieldrin, endrin, endosulfan-II, endrin-aldehyde and endosulfan-sulfate. Pesticide levels in small serum samples from individual Falco sparverius, Sturnella neglecta, Mimus polyglottos and Columbina passerina were quantified. Concentrations ranged from not detected (n/d) to 204.9 pg/microl for some OC pesticides. All levels in the food web in and around cultivated areas showed the presence of pesticides notwithstanding the small areas for agriculture existing in the desert of Baja California peninsula.

Brain regional gamma-aminobutyric acid (GABA) and locomotor activity: effect of long-term aldrin exposure.

Aldrin-induced stimulation of locomotor activity (LA) under nontolerant conditions was restored to control value after 20 or more consecutive days of aldrin administration. In contrast to the inhibition of GABAergic activity with aldrin under short-term conditions as observed in our previous study, the measurement of steady-state level of GABA, the activities of its metabolizing enzymes, turnover and the specific binding of GABA to its receptor in different regions of the brain of rats treated with aldrin (2 or 5 mg/kg/day, po) under long-term (for 30 consecutive days) conditions showed no change in the GABAergic activity in any regions of the rat brain. Moreover, the studies of the interaction between neurotransmitters (using agonist(s) and antagonist(s) of the respective neurotransmitter receptors) showed that long-term administration of aldrin restored the LA to control value by upregulation of central GABAergic activity through the interaction with dopaminergic and cholinergic systems. Thus, this result suggests that long-term aldrin exposure upregulated the central GABAergic activity inhibition under short-term aldrin treatment which may be a cause of restoration of LA stimulated by the short-term aldrin administration to its control value.

Cancer mortality in workers exposed to dieldrin and aldrin: an update.

This study was conducted to investigate the possible long-term health effects, in particular carcinogenic effects, of occupational exposure to the organochlorine insecticides dieldrin and aldrin. We updated an earlier cohort mortality study of 570 employees involved in the production of these insecticides. All of the employees had worked in the production plants between 1 January 1954 and 1 January 1970 and were followed for cause-specific mortality until 1 January 2001. Based on dieldrin levels in blood samples taken during the exposure period, available for 343 workers, individual estimates of the total intake of dieldrin were estimated for all individual subjects in the cohort. The estimated total intake ranged from 11 to 7755 mg of dieldrin, with an average of 737 mg. One hundred and seventy-one workers had died before 1 January 2001, compared with an expected number of 226.6, giving a standardized mortality ratio (SMR) of 75.6 [95% confidence interval (CI): 64.6-87.7]. This deficit in total mortality was mainly attributable to a deficit in cardiovascular disease mortality, but cancer mortality was also lower than expected. The observed number of deaths from rectal cancer was significantly higher than expected (SMR = 300.0; 95% CI: 109.5-649.3), but was most pronounced in the low-intake subgroup and appears to be unrelated to exposure to dieldrin and aldrin. This study reinforces the earlier findings that occupational exposure of workers to significant amounts of dieldrin and aldrin has not led to a higher cancer mortality than would be found in an unexposed population.

[DDT and related pesticides in maternal milk and other tissues of healthy women at term pregnancy]. / DDT y plaguicidas relacionados presentes en la leche materna y otros tejidos de mujeres sanas con embarazos de término.

Ten healthy patients with term pregnancy resolved by abdominal via. During the surgical procedure samples of umbilical chord serum and maternal adipose tissue, were taken. In all the samples, together with the maternal milk collected the day 10 of puerperium, the concentrations of the following organochlorine pesticides, were measured up: (PCC); beta-BHC; gamma-BHC; heptachloride; aldrin; dieldrin, DDE, DDD, DDT and methoxychloride. The identification and quantification of pesticides was done by the comparison with standards certified by NIST (National Institute of Standard Technology). The general characteristics of the participants were: primigestas of 24.1 years aged, married and of a low socioeconomical level. As to the neonates, of 39 weeks of gestational age, female sex; 3,311 g of corporal weight and size of 51.1 cm. In all the analyzed samples at least one of the organochlorine pesticides was present. The results of correlation analysis between DDT concentration, present in the maternal serum with those identified in the adipose tissue and serum from the umbilical chord were highly significant: a = 0.97 and 0.87, respectively. In the maternal milk the highest concentrations of total DDT, were found, average of 2053 ng/g lipidic base, which is 2.8 times more of daily accepted intake. Likewise, DDT concentration in maternal serum kept exponential relation, growing with age (a = 0.99).

Chronic motor neuron disease possibly related to intoxication with organochlorine insecticides.

We report on two patients with a history of chronic exposure to organochlorine insecticides who developed clinical and electromyographic signs and symptoms of chronic motor neuron disease. Measurements of aldrin, lindane and heptachlor confirmed the intoxication. We emphasize the importance of searching for toxic and environmental factors in cases of motor neuron disease especially in Third World countries, where workers usually wear no adequate protective equipment.

Aldrin and dieldrin residues in human fat, milk and blood serum collected from Delhi.

1. Aldrin and dieldrin residues were monitored in the fat, breast milk and blood serum from female residents of Delhi. 2. The average aldrin and dieldrin contents were 0.048 and 0.099 ppb in adipose tissue, 0.003 and 0.060 ppb in breast milk and 0.004 and 0.002 ppb in blood serum, respectively. 3. The older donors contained higher levels of aldrin and dieldrin in their adipose tissue. 4. Primagravidae contained more of these chemicals in their breast milk. 5. A positive correlation was observed between the aldrin concentration in adipose tissue and breast milk, and that in adipose tissue and blood serum. Similarly, a significant correlation was found between dieldrin in adipose tissue and blood serum. 6. The levels of aldrin and dieldrin were low in samples from residents of Delhi when compared to those in developed countries.

Evaluation of prenatal aldrin intoxication in rats.

The aim of the present study was to evaluate the impact of prenatal exposure to low doses of aldrin on physical and behavioral developments of rats (1-21 days old). To detect the possible persistent adversities produced by this exposure, the animals were also tested when adults (90 days old). Plasma determinations of both aldrin and its metabolite dieldrin and histopathological evaluations of brain slices were also performed in adult animals. Pregnant female rats were subcutaneously (s.c.) treated with aldrin (1.0 mg/kg) or with its vehicle (0.9% NaCl solution plus Tween-80) from day 1 of pregnancy until delivery. Results show that prenatal aldrin administration was able to decrease the median effective time (TE50) for incisor teeth eruption and to increase the TE50 for testes descent; other parameters indicative of physical development were not modified. Aldrin and dieldrin were not found in plasma of the adult rats; no differences were observed between control and experimental rats in the cellular and structural organization of the cerebral cortex neurones. Prenatal aldrin administration produced no impairment of adult animal's behavior in an avoidance learning test; nevertheless, the locomotor frequency of the experimental rats was higher than that of controls at 21 and 90 days old. When adults, these experimental rats had their performance in a hole-board apparatus (total number and duration of head-dips) also higher than that of the control ones. It was concluded that prenatal aldrin exposure induced not only developmental changes in the rat pups but also persistent behavioral alterations in adulthood, when the pesticide was not present in these animals.

Human aldrin poisoning

Sixteen patients acutely poisoned with aldrin were examined to evaluate a possible correlation between serum aldrin and diedrin levels and clinical complaints. The patients were classified as having mild (N = 8), moderate (N = 5) or severe (N = 3) poisoning according to clinical symptoms. Concentrations of less than 20 µg/l were usually associated with mild poisoning, which involved complaints such as nausea, vomiting and epigastric pain, whereas concentrations of 100 to 200 µg/l were considered to represent moderate intoxication and were associated with nausea, vomiting, epigastric pain, headache, dizziness, and convulsions. Sever or fatal cases were associated with levels above 700 µg/l. Taken together,these results suggest that serum aldrin diedrin levels can be used as indicators of clinical prognosis after acute poisoning with these insecticides and that convulsions could suddenly occur even in the absence of prodronal signs or symptoms

Human aldrin poisoning.

Sixteen patients acutely poisoned with aldrin were examined to evaluate a possible correlation between serum aldrin and dieldrin levels and clinical complaints. The patients were classified as having mild (N = 8), moderate (N = 5) or severe (N = 3) poisoning according to clinical symptoms. Concentrations of less than 20 micrograms/l were usually associated with mild poisoning, which involved complaints such as nausea, vomiting and epigastric pain, whereas concentrations of 100 to 200 micrograms/l were considered to represent moderate intoxication and were associated with nausea, vomiting, epigastric pain, headache, dizziness, and convulsions. Severe or fatal cases were associated with levels above 700 micrograms/l. Taken together, these results suggest that serum aldrin and dieldrin levels can be used as indicators of clinical prognosis after acute poisoning with these insecticides and that convulsions could suddenly occur even in the absence of prodromal signs or symptoms.

[Acute poisoning by aldrin: relationship between serum levels and toxic effects in humans]. / Intoxicação aguda por aldrin: relação dos níveis séricos com efeitos tóxicos no homem.

In the attempt to correlate clinical findings with serum levels of aldrin, sixteen patients were followed-up after acute intoxication by this agent. Eight of them, males and females, aged from 1 to 37 years, presented no or light symptoms (some discomfort and nausea). The serum of one of these patients was found to contain 16.6 ppb of aldrin and that of another, 1.41 ppb of dieldrin. A group of five patients, aged from two to 30 years, showed symptoms of moderate severity, reporting nausea, vomiting, drowsiness, dyspnea, sweating, mild jerking, rise in blood pressure and convulsions. Of these cases, two were accidental and three were attempted suicides, the majority achieving complete recovery within 24 hours. Serum levels of aldrin were between 6.98 ppb and 26.3 ppb and of dieldrin between 82.00 and 314.18 ppb. We found three severe cases, aged from 21 to 35 years, two attempted suicides and one occupational case. Two of these patients died and one of them presented hypothermia, coma, absence of reflexes and generalized convulsions, and another presented abdominal pain, paleness, sweating, cold extremities, dyspnea, hyperthermia and generalized convulsions. In the first one that died the serum levels were: of aldrin 30.00 ppb and of dieldrin 720 ppb. In the other levels of 747.3 ppb of aldrin and 1,314.00 ppb of dieldrin were found. The third had less serious symptoms and presented serum levels of aldrin of 31.05 ppb and of dieldrin 147.11 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

Intoxicaçäo aguda por aldrin: relaçäo dos níveis séricos com efeitos tóxicos no homem / Acute intoxication by aldrin: relationship between serum levels and toxic effects in men

Para correlacionar o quadro clínico com níveis séricos de aldrin e dieldrin, foram acompanhados 16 pacientes com intoxicaçäo aguda por formulaçäo de aldrin. Oito deles, de ambos os sexos, com idade de 1 a 37 anos, apresentaram apenas sintomas leves como náusea e desconforto, e alguns permaneceram assintomáticos. No soro de um deles foi encontrado 16,6 ppb de aldrin e em outro 1,41 ppb de dielsonolência, dispnéia, sudorese, abalos musculares, elevaçäo da tensäo arterial e episódios isolados de convulsäo, a maioria com restabelecimento do estado de saúde em 24 h. A idade deste grupo variou de 2 a 30 anos e os níveis séricos de aldrin se situaram entre 6,98 ppb e 26,3 ppb, enquanto o dieldrin variou entre 82,00 ppb e 314,18 ppb. Os três outros pacientes desenvolveram um quadro grave de intoxicaçäo correspondendo a duas tentativas de suicídio e um de origem ocupacional, com idades de 21 a 35 anos; dois deles foram a óbito, um apresentando dor abdominal, arreflexia, sudorese, dispnéia, hipertemia, leucocitose no início do internamento que evoluiu para leucopenia severa, convulsöes generalizadas, coma, insuficiência renal aguda, edema agudo de pulmäo e morte no sétimo dia de decorrida a intoxicaçäo; outro apresentou níveis séricos de aldrin de 30,00 ppb e 720 ppb de dieldrin; e outro, com intoxicaçäo mais severa, com êxito letal no terceiro dia de internaçäo, apresentou níveis séricos de 747,3 ppb de aldrin e 1.314,00 ppb de um teor de aldrin sérico de 31,05 ppb e 147,11 ppb de dieldrin...