Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis

Serum Dioxin Concentrations and Age at Menopause

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women’s Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were ≥ 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4–34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3–54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2–118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above

Serum Dioxin Concentrations and Quality of Ovarian Function in Women of Seveso

BACKGROUND: Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we initiated the Seveso Women’s Health Study to study reproductive health. OBJECTIVE: We related TCDD levels measured in sera collected near the time of explosion and ovarian function (ovarian cysts, ovarian follicles, ovulation rate, serum hormones) at follow-up. METHODS: We included 363 women who were 20–40 years of age and nonusers of oral contraceptives. We examined the relationship of 1976 serum TCDD levels with ultrasound-detected ovarian follicles among 96 women in the menstrual follicular phase and serum hormone levels (estradiol, progesterone) among 129 women in the menstrual luteal phase at follow-up. Ovulation was defined by serum progesterone levels > 3 ng/mL. RESULTS: The median serum TCDD level was 77.3 ppt, lipid-adjusted. Serum TCDD was not associated with number or size of ovarian follicles. Of women in the luteal phase, 87 (67%) ovulated. Serum log(10)TCDD was not associated with odds of ovulation [adjusted odds ratio = 0.99; 95% confidence interval (CI), 0.5 to 1.9]. Among those who had ovulated, serum log(10)TCDD was not associated with serum progesterone [adjusted beta (adj-β ) = −0.70; 95% CI, −2.4 to 1.0] or estradiol (adj-β = −1.81; 95% CI, −10.4 to 6.8). CONCLUSIONS: We found no clear evidence that 1976 TCDD exposure was associated with ovarian function 20 years later in women exposed to relatively high levels in Seveso, Italy

Pesticides in house dust from urban and farmworker households in California: an observational measurement study

<p>Abstract</p> <p>Background</p> <p>Studies report that residential use of pesticides in low-income homes is common because of poor housing conditions and pest infestations; however, exposure data on contemporary-use pesticides in low-income households is limited. We conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion.</p> <p>Methods</p> <p>In 2006, we collected up to two dust samples 5-8 days apart from each of 13 urban homes in Oakland, California and 15 farmworker homes in Salinas, California, an agricultural community (54 samples total). We measured 22 insecticides including organophosphates (chlorpyrifos, diazinon, diazinon-oxon, malathion, methidathion, methyl parathion, phorate, and tetrachlorvinphos) and pyrethroids (allethrin-two isomers, bifenthrin, cypermethrin-four isomers, deltamethrin, esfenvalerate, imiprothrin, permethrin-two isomers, prallethrin, and sumithrin), one phthalate herbicide (chlorthal-dimethyl), one dicarboximide fungicide (iprodione), and one pesticide synergist (piperonyl butoxide).</p> <p>Results</p> <p>More than half of the households reported applying pesticides indoors. Analytes frequently detected in both locations included chlorpyrifos, diazinon, permethrin, allethrin, cypermethrin, and piperonyl butoxide; no differences in concentrations or loadings were observed between locations for these analytes. Chlorthal-dimethyl was detected solely in farmworker homes, suggesting contamination due to regional agricultural use. Concentrations in samples collected 5-8 days apart in the same home were strongly correlated for the majority of the frequently detected analytes (Spearman ρ = 0.70-1.00, p < 0.01). Additionally, diazinon and chlorpyrifos concentrations in Salinas farmworker homes were 40-80% lower than concentrations reported in samples from Salinas farmworker homes studied between 2000-2002, suggesting a temporal reduction after their residential phase-out. Finally, estimated non-dietary pesticide intake for resident children did not exceed current U.S. Environmental Protection Agency's (U.S. EPA) recommended chronic reference doses (RfDs).</p> <p>Conclusion</p> <p>Low-income children are potentially exposed to a mixture of pesticides as a result of poorer housing quality. Historical or current pesticide use indoors is likely to contribute to ongoing exposures. Agricultural pesticide use may also contribute to additional exposures to some pesticides in rural areas. Although children's non-dietary intake did not exceed U.S. EPA RfDs for select pesticides, this does not ensure that children are free of any health risks as RfDs have their own limitations, and the children may be exposed indoors via other pathways. The frequent pesticide use reported and high detection of several home-use pesticides in house dust suggests that families would benefit from integrated pest management strategies to control pests and minimize current and future exposures.</p

Maternal exposure to DDT, DDE, and pyrethroid insecticides for malaria vector control and hypospadias in the VHEMBE birth cohort study, Limpopo, South Africa

Hypospadias is the ectopic opening of the urethra on the penis or scrotum. Exposure to estrogenic and/or anti-androgenic chemicals in utero may play an etiologic role. DDT and the pyrethroids cypermethrin and deltamethrin, are used to control malaria. DDT is estrogenic and its breakdown product DDE is anti-androgenic; cypermethrin and deltamethrin can also disrupt androgen pathways. We examined the relationship between maternal exposure to these insecticides during pregnancy and hypospadias among boys participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) in Limpopo Province, South Africa. We measured peripartum levels of p,p'-DDT and p,p'-DDE in maternal serum and urinary pyrethroid metabolites. We conducted urogenital examination on 359 one-year-old boys. A total of 291 (81.0 %) had phimosis, which prevented full urogenital examination, leaving a final sample of 68 boys for determination of the presence of hypospadias. Diagnosis was based on concordance of two independent physicians. We identified hypospadias in 23 of the 68 boys (34 %). Maternal urinary concentrations of cis-DCCA and trans-DCCA metabolites of cypermethrin and other pyrethroids, were associated with an increased risk for hypospadias, but the other metabolite 3-PBA was not (adjusted relative risk per 10-fold increase = 1.58, 95 % CI 1.07–2.34; 1.61, 95 % CI 1.09–2.36; and 1.48, 95 % CI 0.78–2.78, respectively). No associations were found between p,p'-DDT, p,p'-DDE, 3-PBA or cis-DBCA and hypospadias. We observed a high prevalence of hypospadias among boys without phymosis. Boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias. Our findings may have global implications given that pyrethroid insecticides are widely used for malaria control, in agriculture and for home use.http://www.elsevier.com/locate/scitotenvhj2023School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

PON1 and Neurodevelopment in Children from the CHAMACOS Study Exposed to Organophosphate Pesticides in Utero

BackgroundParaoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.ObjectiveWe determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.MethodsWe measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds' blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.ResultsChildren with the PON1(-108T) allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1(-108T) allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.ConclusionPON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure

Maternal Perception of Child Weight Among Mexicans in California and Mexico

The prevalence of childhood overweight is high in Mexican immigrant communities in the United States. Understanding mother’s perceptions of child weight in immigrants’ country of origin may help to understand this high prevalence. The goal of this study was to examine and compare mothers’ perception of weight in Mexico (MX) and in an immigrant community in California (CA). We assessed perceptions of child weight using a pictorial scale with 314 mothers of 5-year-old children in MX and 60 mothers of 5 year-old-children in CA. We compared maternal reports with children’s objectively measured weight. Using chi-square and Analysis of Variance, we investigated associations of maternal perception of and satisfaction with weight according to socio-demographic characteristics. Mothers were more likely to underestimate their children’s weight in CA than in MX. On average, CA mothers wanted their children to be smaller than they currently were and mothers in MX wanted their children to be bigger than they currently were. This differed by weight status in CA with mothers of normal weight and at-risk-for-overweight children wanting them to be bigger and mothers of overweight children wanting them to be smaller. In order for programs to be effective, mothers must be able to recognize their children as overweight and want to address it. Because underestimation of weight and a desire for a larger size is common in this population, programs to address overweight may be more effective if they focus on alternative benefits of weight control strategies, such as healthy child development

Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization

The dorsal striatum plays an important role in the development of drug addiction; however, a precise understanding of the roles of striatopallidal (indirect) and striatonigral (direct) pathway neurons in regulating behaviors remains elusive. Using a novel approach that relies on the viral-mediated expression of an engineered GPCR (hM4D), we demonstrated that activation of hM4D receptors with clozapine-N-oxide (CNO) potently reduced striatal neuron excitability. When hM4D receptors were selectively expressed in either direct or indirect pathway neurons in rats, CNO did not change acute locomotor responses to amphetamine but altered behavioral plasticity associated with repeated drug treatment. Specifically, transiently disrupting striatopallidal neuronal activity facilitated behavioral sensitization whereas decreasing excitability of striatonigral neurons impaired its persistence. These findings suggest that acute drug effects can be parsed from the behavioral adaptations associated with repeated drug exposure and highlight the utility of this approach for deconstructing neuronal pathway contributions to behaviors such as sensitization