Biomonitoring Organochlorine Pesticides in Didelphis virginiana from Yucatan, Mexico by GC-ECD.

The aim of the present work was to apply a validated methodology for the detection of organochlorine pesticides in Didelphis virginiana (Virginia opossum) serum samples collected in Yucatan, Mexico. Recent studies performed to investigate the presence of Organochlorines (OCLs) in water, human blood and milk, and animal tissues from Yucatan have shown that the OCLs concentrations are high and can be associated with potential human health risk. Since opossum is considered an important synanthropic species in Yucatan, 40 opossum serum samples were analyzed by gas chromatography with electron capture detector. The most common OCLs found in opossum sera were lindanes, chlordanes, drines, and endosulfan. Heptachlor, heptachlor epoxide, and lindanes were found at the highest concentrations, while dichlorodiphenyl trichloroethane and its metabolites were found at the lowest concentrations in the samples. The good linearity, precision, and accuracy obtained in the evaluated parameters in the extraction and chromatographic methods support its application for the monitoring of OCLs pesticides in populations of opossums and other wild species in Yucatan.

Level of endosulfan among women in Talwandi Sabo Block of Southern Punjab, India.

Endosulfan is one of the most prevalent organochlorine pesticides used in the agricultural sector in the developing countries including India. It affects the physiological functioning of different organ systems including nervous, immune, hepatic, and reproductive system. Realizing the safety and health concern, restrictions have been imposed at various levels, but the usage has still continued in the plantation crops. Owing to pesticide beneficiary of north India, the cotton belt commonly called the Malwa region of Punjab was evaluated for identifying the levels of Endosulfan in the blood samples of women working in agricultural fields. Gas chromatograph with electron capture detector was used for detecting the levels of endosulfan metabolites among twenty active female workers. The mean level of endosulfan recorded in the tested population was observed to be 2.22 ppb. It is difficult to draw a certain conclusion based on these findings because the subjects were less in number. However, detection of even very low concentrations of endosulfan residues signifies its continued accessibility to the women population. Encouragement of more such population-based research needs to be adopted to determine the body burden of such pesticides in humans. The effective implementation of the ban on Endosulfan could be checked by a combined retrospective and prospective study to infer a justifiable impact.

Plaguicidas e hipotiroidismo en agricultores en zonas de cultivo de plátano y café, en Quindío, Colombia / Pesticides and hypothyroidism in farmers of plantain and coffee growing areas in Quindio, Colombia

RESUMEN Objetivos Determinar relación entre hipotiroidismo y plaguicidas en sangre. Metodología Estudio de corte transversal, en agricultores y sus compañeros(as) permanentes en municipios productores de plátano y café. Se calculó muestra representativa. Se realizaron pruebas de función tiroidea, se utilizó un lector de ELISA Stat Fax 303/Plus, en una longitud de onda 450 nm. Se determinó la residualidad de plaguicidas organoclorados, se implementó un método de microextracción dispersiva en fase líquida (DLLME) asistida por sonicación, y se empleó cromatografía de gases con detector de micro captura de electrones (GC-µECD) para el análisis. Resultados Se incluyeron 819 participantes, 58,7% hombres y 41,3% mujeres; promedio de edad 48,1 años. Prevalencia de hipotiroidismo manifiesto 1,2% y de hipotiroidismo subclínico 6,7%, mayor prevalencia en personas mayores de 60 años (2,6% y 8,9% respectivamente). Se encontró asociación no causal de hipotiroidismo subclínico con plaguicidas organoclorados 4,4'-DDE (sig.0,006), Heptacloro (sig.0,04), y Endosulfán I (sig.0,02). Los anticuerpos antiperoxidasa (Anti TPO) ≥ 60 lU/ml se asociaron con h. subclínico, OR 2,6. Conclusiones La prevalencia de hipotiroidismo hallada es similar a lo referido en la literatura, es menor que en áreas urbanas; la prevalencia de hipotiroidismo subclínico es mayor y con riesgo de progresión a hipotiroidismo franco cuando se relaciona con Anti-TPO positivos, razón por la cual se requiere seguimiento en estos pacientes. Se asociaron a h. subclínico 3 plaguicidas organoclorados. Se recomienda tamizaje de TSH en personas de 40 y más años sobre todo si están expuestas a los agroquímicos mencionados.(AU)

ABSTRACT Objectives To establish the correlation between hypothyroidism and blood pesticide levels. Materials and Methods Cross-sectional study in agricultural workers and their permanent partners in plantain and coffee producing municipalities as reference population. A representative sample was estimated and thyroid function tests were performed using ELISA Stat Fax 303/Plus reader, at a wavelength of 450 nm. Organochlorine pesticide residuality was determined, a dispersive liquid-liquid microextraction (DLLME) assisted by sonication was implemented, and a gas chromatography-micro-electron capture detector (GC-pECD) was used for the analysis. Results 819 participants, 58.7% men and 41.3% women were included; their average age was 48.1 years. Prevalence of symptomatic hypothyroidism (1.2%) and subclinical hypothyroidism (6.7%) was observed, with a higher prevalence in people older than 60 years (2.6% and 8.9%, respectively). Non-causal association was found between subclinical hypothyroidism and the organochlorine pesticides 4,4'-DDE (sig.0,006), Heptachlor (sig.0,04), and Endosulfan I (sig.0,02). Antiperoxidase (Anti TPO) antibodies ≥60 lU/ml were associated with subclinical hypothyroidism (OR 2.6). Conclusions The prevalence of hypothyroidism in the studied population is similar to that reported in the literature, and lower than in urban areas. In turn, the prevalence of subclinical hypothyroidism is higher and positive anti-TPO values are related to risk of progression to frank hypothyroidism, which is why follow-up is required in these patients. Three organochlorine pesticides were associated with subclinical hypothyroidism. TSH screening is recommended in people aged 40 and over, especially if they are exposed to the aforementioned agrochemicals.(AU)

Serum concentrations of organochlorine compounds and predictors of exposure in children living in agricultural communities from South-Eastern Spain.

BACKGROUND: Information on exposure levels to organochlorine compounds (OCs) in child population is limited, despite their greater vulnerability to the adverse health effects of these chemicals. OBJECTIVE: To determine serum concentrations of 10 OCs (including organochlorine pesticides and polychlorinated biphenyls -PCBs-) in children living in agricultural communities from Almería (South-Eastern Spain), and to identify the main predictors of exposure related to socio-economic characteristics, diet and lifestyle. METHODS: A cross-sectional study was conducted on 133 children aged 6-11 years selected from public schools of the study area. OCs compounds were determined in serum samples by GC/ECD. Anthropometric measures were obtained during sample collection. Information on sociodemographic characteristics, parental occupation, residential history, lifestyle and frequency of food consumption, among other relevant factors, was obtained by questionnaires administered to the mothers. RESULTS: Geometric means of serum concentrations (ng/ml) were 0.11 for ß-hexachloro-cyclohexane (ß-HCH), 0.09 for endosulfan, 0.20 for endosulfan-ether, 0.51 for hexachorobenzene (HCB), 0.08 for mirex, 0.06 for oxychlordane, 0.36 for p,p'-DDE, 0.20 for PCB 138, 0.36 for PCB 153, and 0.45 for PCB 180. Percentage of samples above the limit of detection (0.05 ppb) ranged from 32 (ß-HCH) to 100 (HCB). A high variability in OC levels depending on the compound was observed between our results and others found in similar studies carried out in children. Variables related to fish consumption were found to be the major dietary determinant of PCB 138, p,p´-DDE, endosulfan-α, ß-HCH, mirex and oxychlordane levels. CONCLUSIONS: Children participating in this study showed detectable levels of many OC, despite these compounds are no longer used. Their presence in children serum can be explained by their high lipophilicity and environmental persistence, leading to contamination of fatty food. In this line, fish consumption seemed to be the most relevant determinant of OC levels found in our study.

Pesticide genotoxicity in cotton picking women in Pakistan evaluated using comet assay.

To control agricultural pests and meet the increasing food demands, pesticides use has been increased substantially over time. Although pesticides are relatively specific to their targets, they can affect non-target organisms and are hazardous for the population around the application areas particularly to the individuals engaged in different types of agricultural activities. This situation is worse in developing and under-developed countries where personal protective equipment is merely used and regulatory guidelines are hardly practiced. In the present study, DNA damage in women exposed to pesticides while picking cotton with bare hands was assessed using single cell gel electrophoresis assay or comet assay. The presence of pesticides in blood serum of exposed individuals was also analyzed using high-performance liquid chromatography. Blood samples were collected from 138 (69 exposed and 69 control) randomly selected females from a major cotton growing area (Bahawalpur District) of the Punjab province of Pakistan. DNA damage, as determined by the mean comet tail length, was significantly higher (p < 0.001) in the exposed group compared to the unexposed. A positive correlation of DNA damage with age and exposure time was also observed. Residues of three pesticides, cyhalothrin, endosulfan, and deltamethrin found significantly higher (p < 0.001) in the serum samples of the exposed group compared to the unexposed. It was observed that the groups with higher mean comet tail length also had a higher concentration of pesticides in their serum samples indicating a positive association of DNA damage and pesticide exposure. The present study suggests that exposure to pesticides leads to DNA damage.

Early postnatal exposure to endosulfan interferes with the normal development of the male rat mammary gland.

Our aim was to evaluate whether postnatal exposure to endosulfan (ENDO) modifies mammary gland (MG) development in pre- and post-pubertal male rats. From postnatal day 1 (PND1) to PND7, male rats were injected subcutaneously every 48h with either corn oil (vehicle) or 600µg ENDO/kg.bw. On PND21 and PND60, MG and blood samples were collected. Estradiol (E2) and testosterone (T) serum levels, MG histology, collagen fiber organization, proliferation index, and estrogen (ESR1) and androgen receptor (AR) expressions were evaluated. On PND21, E2 and T levels were similar between groups, whereas MG area, perimeter, number of terminal end buds and ESR1 expression were increased in ENDO-exposed rats. These changes were associated with alveolar development and increased organized collagen in the stroma. On PND60, a higher proliferation index in ENDO-exposed rats was correlated with a more developed lobuloalveolar structure. Hyperplastic alveoli and, hyperplastic ducts surrounded by a dense stroma were also observed in this group. T levels and ESR1 expression were similar between groups, whereas E2 levels and AR expression were decreased in ENDO-exposed rats. The exposure to ENDO in the first week of life interferes with the normal development of the MG and induces pre-malignant lesions in post-pubertal male rats.

Organochlorine Pesticides in Gonad, Brain, and Blood of Mice in Two Agricultural Areas of Sinaloa.

The adverse effect of pesticides on non-target wildlife and human health is a primary concern in the world, but in Mexico, we do not know which wildlife species are at the greatest risk. The aim of this study was to determine organochlorine pesticides in mice of two agricultural fields in Sinaloa, Culiacan and Guasave. Procedures of extraction, analysis, and quantification were followed according to the modified EPA 8081b method. In three mouse tissues (gonad, brain, and blood), γBHC and decachlorobiphenyl with a frequency higher than 50% and endosulfan sulfate with 43% were observed. The wildlife fauna living in agricultural areas are at great risk due to: (1) diversity of the chemicals used for pest control, like mice, and (2) variety of organochlorine pesticides in direct or indirect contact with non-target organisms, affecting the health of animals and humans (toxic effects and accumulation).

Organochlorine pesticide exposure in mothers and neural tube defects in offsprings.

We explored the association between maternal exposure to organochlorine pesticides and neural tube defects (NTDs) in the offspring. Blood was collected from 35 mothers and their offsprings with NTDs (case group) and from 35 mothers-neonate dyads without congenital anomalies (control group). The median blood levels of DDE, t-HCH and endosulphan in mothers in the case group and of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), total hexachlorocyclohexane (t-HCH) and endosulfan in the neonates with NTDs were significantly higher. Neonates with NTDs had 3.6 times more chances of having blood levels of endosulfan above the median level of the control group. Mothers delivering offsprings with NTDs had 11.3 times greater chances of having DDE levels above the median concentration in the control group. We recommend a restrained use of organochlorine pesticides like DDT, DDE, and endosulfan, while monitoring the expectant mothers closely for birth defects like NTDs.

Prenatal exposure to organochlorine pesticides and infant birth weight in China.

In utero exposure to organochlorine pesticides (OCPs) is thought to be potentially harmful to fetal development. We aimed to investigate the associations of maternal and cord serum OCPs levels with infant birth weight in China. In this study, we measured serum levels of 18 OCPs in 81 mother-infant pairs, including DDT, hexachlorocyclohexanes (BHC), hexachlorobenzene (HCB), heptachlors, chlordanes, endosulfan-I, and mirex using a high-resolution-gas-chromatography with high-resolution-mass-spectrometry method. We found that p,p'-DDE and ß-BHC had the highest detection rate in both maternal and cord blood serum (97.2% and 96.7%, respectively), followed by HCB (93.0%, 51.7%), p,p'-DDT (88.7%, 36.7%), and p,p'-DDD (83.1%, 60.0%). Among all OCPs, the concentration of p,p'-DDE was the highest (mothers geometric mean (GM): 203.54ngg(-1), newborns GM: 116.14ngg(-1)), followed by HCB (70.62ngg(-1), 65.16ngg(-1)), and ß-BHC (67.67ngg(-1), 33.39ngg(-1)). Multiple linear regression analyses showed that each 1ngg(-1) increment of cord serum p,p'-DDE, total DDT, and ß-BHC was associated with a 0.10g, 0.10g, and 0.92g decrease in infant birth weight, respectively, and as the cord serum concentrations of p,p'-DDT, p,p'-DDD, HCB and mirex increased, the infant birth weight was also decreased, although the associations were not statistically significant due to the relatively small sample size. These results suggest that p,p'-DDE, ß-BHC, and HCB were the predominant OCPs in the serum of Chinese pregnant women and cord blood of their newborns. Prenatal exposure to DDT, ß-BHC, HCB, and mirex were associated with a decrease in birth weight, but these results need validation in larger sample-sized studies.

Association of CYP1A1, CYP1B1 and CYP17 gene polymorphisms and organochlorine pesticides with benign prostatic hyperplasia.

It is well established that steroidal hormones (testosterone and estrogen) increase benign prostatic hyperplasia (BPH) risk. Cytochrome P450 (CYP) enzymes especially CYP1A1, CYP1B1 and CYP17 metabolize these hormones. Apart from that, several endocrine disrupting organochlorine pesticides (OCPs) are reported to mimic the activity of these steroidal hormones. Therefore, functional polymorphisms in these genes and exposure to such pesticides may increase BPH risk further. Our study included 100 newly diagnosed BPH subjects and 100 age-matched healthy male controls. CYP1A1, CYP1B1 and CYP17 polymorphisms were studied using PCR-RFLP and allele-specific PCR method. OCP levels in blood were analyzed by gas chromatography (GC). Levels of p,p'-DDE and endosulfan α were found to be significantly higher amongst BPH subjects as compared to controls (p-values=0.001 and 0.03 respectively) and CYP17 polymorphism was observed to be significantly associated with BPH subjects as compared to controls (p-values=0.03), indicating that these factors may be important risk factors for BPH. However, further studies are required before unequivocal conclusion.

Regional variation in pesticide concentrations in plasma of delivering women residing in rural Indian Ocean coastal regions of South Africa.

Exposure to pesticides places pregnant women and the developing foetus at the highest risk. The objective of this study is to obtain an exposure assessment by investigating levels of pesticides in blood plasma of delivering women. We report on the concentrations of α, ß, γ HCH, endosulfan, HCB and the pyrethroids: cis-permethrin, cyfluthrin, cypermethrin and deltamethrin found in the maternal blood plasma of delivering women (n = 241) in three coastal sites of KwaZulu Natal. γ-HCH and endosulfan 1 and 2 were the most dominant pesticides in all three sites. Significantly, higher levels of γ-HCH and endosulfan were found in site 3 (vicinity of Empangeni) compared to the other two sites (p < 0.05). The GM levels for γ-HCH, endosulfan 1 and 2 were 956, 141 and 21 ng g(-1) lipids in site 3, respectively. The pyrethroid pesticides, HCB, α-HCH and ß-HCH were detected in less than 31% of the samples in all sites. γ-HCH correlated positively and strongly to both endosulfan 1 and 2 (r > 0.47), indicating a common source of exposure. The high levels of γ-HCH and endosulfan in maternal plasma samples in site 3 indicate the current and on-going exposure, which is of great concern for reproductive health and prenatal exposure.

A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides.

OBJECTIVES: Organochlorine pesticides (OCPs) and oxidative stress are reported to be associated with adverse reproductive outcomes. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous toxins including OCPs. OCPs are endocrine disrupter and prenatal exposure to them may be associated with fetal growth restriction (FGR). The objectives of the present study were (i) to determine the frequencies of polymorphic alleles of GSTM1 and GSTT1 genes in women with idiopathic FGR, (ii) to analyze the maternal and cord blood levels of the OCPs, and (iii) to identify the gene environment interaction that increases the risk of FGR. STUDY DESIGN: Maternal and cord blood samples of 50 FGR cases (birth weight <10 percentile for gestational age as per Lubchenco's growth chart) and equal number of normal pregnancies who were occupationally non exposed to OCPs and excluding all the known high risk factors such as anemia, hypertension, antiphospholipid antibody syndrome, medical disease, dietary habit, living style, parity, and BMI. The collected samples at the time of delivery/after delivery were analyzed for OCPs levels by gas chromatography and polymorphic analysis for GSTM1/GSTT1 gene using multiplex PCR. RESULTS: Significantly higher levels of α,ß,γ-HCH and p,p'-DDT were found in maternal blood and significantly higher levels of ß and γ-HCH and p,p'-DDT were found in cord blood of FGR cases as compared to controls. The genotypic distribution of GSTM1/GSTT1 was almost similar in both the groups, but the frequency of GSTM1-/GSTT1- (null) genotype was significantly higher in FGR cases as compared to controls (p<0.05, OR=6.42). When interaction between GSTM1/GSTT1 genes polymorphism-OCPs levels and birth weight (gene-environment interaction) was ascertained, a significant association was seen between ß-HCH and GSTM1- genotype with reduction in birth weight of 213g. CONCLUSION: Higher levels of OCPs in pregnant women may be considered as an important aetiological factor in 'idiopathic' FGR. GST polymorphism can influence the relationship between prenatal exposure to pesticides and FGR. The present study provides evidence that polymorphism in xenobiotic metabolising genes may modify the effect of environmental health hazards and increase the risk of FGR.

Effects of pesticides used in agriculture on the development of precocious puberty.

The present study aims to evaluate the effects of pesticides on premature breast development. Forty-five girls (group 1) with premature breast development living in the Menderes region, where greenhouse cultivation is the main income, 16 girls (group 2) living in Izmir city with early puberty, and 33 girls (group 3) who had no signs of puberty were included in the study. Endosulphan 1, endosulphan 2, endosulphan sulphate, methoxychlor, vinclozolin, 4,4-dichlorodiphenyldichlorethylene (DDE), 4,-dichlorodiphenyltrichloroethane (DDT), and 2,4-DDT were evaluated in the serum and adipose tissues of the groups by using a gas chromatography-mass spectrometry method. With the exception of 4,4'-DDE, the pesticides studied were undetectable in the serum and adipose tissue samples. The levels of basal luteinizing hormone (LH), stimulated LH, follicle-stimulating hormone, and the long axis of the uterus and both ovaries were significantly different in the girls who had premature thelarche and detectable 4,4'-DDE levels compared to the girls who had premature thelarche and undetectable 4,4'-DDE levels in serum and adipose tissues. The presence and levels of pesticides in serum and adipose tissues were not related to precocious puberty (PP). The mechanisms that lead to PP may also result in obesity, and obesity may be the underlying cause for PP in this group.

Organochlorine pesticide exposure among agricultural workers in Colombian regions with illegal crops: an exploration in a hidden and dangerous world.

A previous study suggested that banned organochlorine pesticides were being used to protect illegal crops from pests. The study herein explored the exposure of individuals living in a region with such crops. Samples from 99 individuals were collected during 2005 and 2006 and organochlorine pesticides were quantified using chromatography in serum samples. We detected heptachlor (72.73%), 4,4-DDE (19.19%), aldrin (15.15%), γ-chlordane (12.12%), dieldrin (11.11%), α-chlordane (10,10%), α-endosulfan (8.08%), endosulfan (6.06%), ß-endosulfan (5.05%), oxychlordane (3.03%), 4,4-DDT (3.03%), and 2,4-DDT (2.02%). Heptachlor had a skewed and negative distribution (median: 8.69 ng/l and maximum: 43.8 ng/l). A two-dimensional biplot suggested that mixtures present were endosulfan/4,4-DDT, aldrin/γ-chlordane, and oxychlordane/ß-endosulfan/dieldrin. We did not identify variables associated with exposure levels. These data suggest that banned organochlorine pesticides are used. This is an example of research in a war context, where the problems related with pesticides are complex, and their implications go beyond a toxicological or epidemiological viewpoint.

Pesticide exposure and blood endosulfan levels after first season spray amongst farm workers in the Western Cape, South Africa.

The study investigated serum endosulfan changes resulting from occupational exposure to the pesticide on farms. Eight applicators and 17 non-applicators were tested (serum endosulfan, anthropometry, short exposure questionnaire) before and after the first day of seasonal spraying. Task-based job exposure matrix (JEM) estimates were calculated. Mean baseline serum endosulfan (530 +/- 0.05 microg/L) was high. Increases in post-spraying endosulfan levels (IPSE) were higher in applicators (mean = 60 +/- 90 microg/L) than in non-applicators (mean = 3.5 x 10(- 6)+/- 90.0 microg/L) adjusting for age (beta = 54.0, p = 0.162, R(2) = 0.22). There was a weak positive relationship between IPSE and JEM estimates. IPSE occurred in applicators and non-applicators and were higher in applicators. The validity of the JEM weightings and characterization of other routes of pesticide exposure require further investigation.

Endosulfan and other organochlorine pesticide residues in maternal and cord blood in North Indian population.

Humans are exposed to various environmental chemicals such as organochlorine pesticide residues, heavy metals, polychlorinatedbiphenyls (PCBs) etc. There is paucity of data regarding the present blood levels of organochlorine residues in North Indian population with reference to reproductive health. The present study was designed to analyze the levels of organochlorine pesticide residues in maternal and cord blood samples of normal healthy women with full term pregnancy to gain insight into the current status of pesticide burden in newborns. Hexachlorocyclohexane (HCH) contributed maximum towards the total organochlorine residues present in maternal and cord blood followed by endosulfan, pp' DDE and pp' DDT being the least. This is also the first report indicating endosulfan levels in this population. Our data indicates a transfer rate of 60-70% of these pesticides from mothers to newborns and this high rate of transfer of pesticides is of great concern as it may adversely affect the growth and development of newborn.

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.

A physiologically based pharmacokinetic model for endosulfan in the male Sprague-Dawley rats.

Endosulfan, an organochlorine (OC) insecticide belonging to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. To date, no physiologically based pharmacokinetic (PBPK) model has been located for endosulfan in animal species and humans. The estimation by a mathematical model is essential since information on humans can scarcely be obtained experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of (14)C-Endosulfan to male Sprague-Dawley rats. The model was parameterized by using reference physiological parameter values and partition coefficients that were determined in the experiment and optimized by manual adjustment until the best visual fit of the simulations with the experimental data were observed. The model was verified by simulating the disposition of (14)C-Endosulfan in vivo after single and multiple oral dosages and comparing simulated results with experimental results. The model was further verified by using experimental data retrieved from the literature. The present model could reasonably predict target tissue dosimetries in rats. Simulation with three-time repeated administration of (14)C-Endosulfan and experimental data retrieved from the literature by the constructed model fitted fairly well with the experimental results; thus suggesting that the newly developed PBPK model was developed. Sensitivity analyses were used to determine those input parameters with the greatest influence on endosulfan tissue concentrations.

Endosulfan and its metabolites in fertile women, placenta, cord blood, and human milk.

Although industrialized nations have restricted or banned many organochlorine pesticides, some of these chemicals (e.g., endosulfans) are still used, on the assumption that they pose little threat to the environment, wildlife, or human health. According to available information, Spain is the main consumer of endosulfans within the European Union, accounting for almost half of the total consumption. Reports on human exposure in Southern Spain to persistent bioacumulable organochlorine pesticides have indicated considerable exposure to endosulfans. The present study investigated the presence of endosulfan I, endosulfan II, and endosulfan metabolites in fatty and non-fatty tissues and fluids from women of reproductive age and children in Southern Spain. The highest concentration of commercial endosulfan I and endosulfan II was found in adipose tissue, with a mean value (I+II) of 17.72 ng/g lipid, followed by human milk, with a mean value (I+II) of 11.38 ng/mL milk. These findings support the lipophilicity of these chemicals and their elimination by milk secretion. The concentration in the placenta homogenate was similar to that in the blood from the umbilical cord (7.74 and 6.11 ng/mL, respectively) and reflected their lower fat content. Endosulfan diol and endosulfan sulfate were more frequently found in placenta homogenate, with a mean concentration of 12.56 and 3.57 ng/mL, respectively, and in blood from umbilical cord, at 13.23 and 2.82 ng/mL, respectively. Therefore, women of reproductive age in Southern Spain appear to be currently exposed to endosulfans. Because these chemicals can be mobilized during pregnancy and lactation, further research is warranted to investigate the health consequence in children resulting from exposure to chemicals suspected of immunotoxic, neurotoxic, or endocrine-disrupting effects.

Analysis of endosulfan and its metabolites in rat plasma and selected tissue samples by gas chromatography-mass spectrometry.

A method has been developed for the determination of trace levels of alpha-endosulfan, beta-endosulfan, endosulfan sulfate, and endosulfan diol in rat plasma and tissue samples. Endosulfan and its metabolites in the plasma samples were extracted with solid-phase extraction Chromabond-end-capped C18 cartridges and analyzed by a Shimadzu QP-5050A gas chromatograph-mass spectrometer (GCMS) with quadrupole detector in selected-ion-monitoring mode. The analysis of endosulfan and its metabolites in liver and kidney samples involved solvent extraction, Florisil solid-phase-extraction cleanup, and quantitation by GCMS. Recovery experiments for the plasma and tissue samples were conducted over concentration ranges of 10-100 ng mL(-1) and 100-1000 ng mL(-1), respectively. The method was applied to the analysis of trace levels of endosulfan and its metabolites in plasma and tissue samples collected from an animal study. Trace levels of alpha-endosulfan and beta-endosulfan in the ranges of undetectable to 3.11 microg g(-1) and undetectable to 1.19 microg g(-1), respectively, were detected in the kidney samples, whereas trace levels of endosulfan sulfate in the range of 0.02-0.22 microg g(-1) were detected in the liver samples of rats. Neither endosulfan nor its metabolites was detected in any of the plasma samples.