Visuospatial processing and fine motor function among 7-years old Guadeloupe children pre- and postnatally exposed to the organochlorine pesticide chlordecone.

BACKGROUND: Chlordecone is an organochlorine that was largely used as an insecticide to control a species of root borers, the Banana weevil (Cosmopolites sordidus), in the French West Indies, Guadeloupe and Martinique. Its molecules have been shown to be very persistent in the environment as pollution in soils leading to contamination of water sources and foodstuff will last for several decades. Our team previously reported associations between prenatal chlordecone exposure and poorer fine motor development at two points in time during infancy. OBJECTIVE: To document whether effects of prenatal exposure to chlordecone previously reported persists until middle-childhood, and whether deleterious effects are observed in domain of visual processing. Associations with postnatal exposure and sex-specific vulnerabilities were also investigated. METHODS: We examined 410 children from the TIMOUN mother-child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children's blood at age 7 years. Fine motor function was assessed using the Bruininks Oseretsky Test of Motor Proficiency Second Edition (BOT-2). The Computerized Adaptive Testing System (CATSYS) was used to evaluated postural hand tremor, while non-verbal visuospatial processing was measured using the Stanford Binet copying (S-B copying) test. We used adjusted multiple linear regressions to test the relationship between children's scores and both continuous and categorical blood chlordecone concentrations, adding child sex as a moderator in continuous models. RESULTS: Cord chlordecone concentrations are associated with a regular frequency pattern of subtle hand tremors in both hands, and not related to visual processing and fine motor precision. Chlordecone concentrations in blood sample collected at testing time are associated with poorer visual processing when copying geometric figures, but not significantly related to poorer fine movement precision in tasks requiring pencil, scissors and paper. No sex-specific vulnerability was reported in any of the outcomes. CONCLUSIONS: These results at school aged expand those previously reported in the same cohort during infancy at age 7- and 18 months, and corroborate the negative effects of chlordecone exposure on fine motor function in absence of intoxication. Our results support the need to continue public health efforts aimed at reducing exposure especially among women of child bearing age and young children.

Characterization and quantification of chlordecone elimination in ewes.

To reduce the exposure of the French West Indies population to the organochlorine insecticide chlordecone (Kepone; CLD), the contamination of currently consumed foodstuffs must be reduced. Depuration of contaminated animals before slaughter could be a strategy to obtain safe animal products. The aim of this study was to characterize and quantify CLD elimination in contaminated ewes during depuration process. Experiments A and B consisted in a single intravenous (i.v.) administration of CLD (n = 5) and CLDOH (chlordecol; n = 3) followed by a 84-d and 3-d depuration period respectively with collection of blood, faeces and urine samples. After CLD administration, CLD and conjugated-CLDOH (CLDOH-C) were quantified in serum and urine and CLD and CLDOH were quantified in faeces. Based on calculations of faecal, urinary and body clearances of CLD and CLDOH-C, faeces appeared as the major route of CLD excretion with 86 % of the CLD administered dose eliminated in faeces, either as CLD (51 %) or as CLDOH (35 %).

Endocrine disrupting-chemicals and biochemical recurrence of prostate cancer after prostatectomy: A cohort study in Guadeloupe (French West Indies).

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.

Toxicokinetics of chlordecone in goats: Implications for risk management in French West Indies.

The former use of chlordecone (CLD) in the French West Indies has resulted in long-term pollution of soils. CLD is known to be potentially transferred towards animal products of animals reared outdoors, mainly through accidental soil ingestion. Several studies indicate that soil bound CLD is bioavailable when administered to farm animals. Currently there is a need to quantify the level of CLD absorption and its toxicokinetic characteristics in the ruminant and particularly in the goat. These are considered as important farm species in the French West Indies. The objective of this study was to evaluate the absorption rate and the half-life of CLD in the non-lactating goat. The goats were administered either intravenously (i.v., n = 6) or orally (p.o., n = 6) one dose (1 mg kg-1 body weight) of CLD. Blood samples were collected at defined times up to 160 days post-dosing. CLD was analyzed in serum by high-resolution gas chromatography. A comparison of the area under the serum concentration-time curves (AUC) showed that the i.v. route is equivalent to the oral route. Thus, CLD is considered almost completely absorbed after p.o. administration, as shown by the mean absolute bioavailability. The comparison between the pharmacokinetic profiles of CLD following oral and intravenous dose showed a difference during the first 14 days and a similar kinetic after this period. The half-life of CLD in serum was close to 20 days. These results highlight a possible strategy of decontamination due to the short half-life of CLD, obtained in dry goats that did not excrete fat matter.

Prenatal exposure to chlordecone, gestational weight gain, and birth weight in a Guadeloupean birth cohort.

BACKGROUND: Chlordecone is a persistent organochlorine insecticide with well-defined estrogenic properties. It was intensively used in the French West Indies until 1993 to control the banana root borer. Because of the long-term contamination of soils and water, the population is currently exposed to chlordecone through food consumption. Chlordecone has been found in the blood of pregnant women and in cord blood. It has been shown to be an endocrine-disrupting chemical and exposure during pregnancy may affect fetal growth. OBJECTIVES: The objective of our study was to examine the association between prenatal exposure to chlordecone and fetal growth based on the TIMOUN birth cohort conducted in Guadeloupe, with a focus on the potential modification of this relationship by maternal body mass index (BMI) and gestational weight gain (GWG). METHODS: Chlordecone was determined in cord plasma at birth in 593 babies. Birth weight was the indicator of fetal growth. Maternal pre-pregnancy BMI and GWG were determined. Adherence to GWG recommendations of the US Institute of Medicine based on maternal pre-pregnancy BMI was assessed. Birth weight was analyzed relative to cord blood chlordecone levels using linear and non-linear regression models. RESULTS: Overall chlordecone in cord blood was not associated with birth weight, but we found an interaction between chlordecone exposure with GWG and adherence to GWG recommendations. After stratification by GWG, we found a significant U-shaped association between birth weight and chlordecone exposure, within the upper quartiles of GWG or excessive GWG. CONCLUSION: Chlordecone exposure may affect fetal growth, particularly when excessive GWG is present.

Non-dioxin-like Polychlorinated Biphenyls (PCBs) and Chlordecone Release from Adipose Tissue to Blood in Response to Body Fat Mobilization in Ewe (Ovis aries).

Understanding how persistent organic pollutants (POPs) are released from adipose tissue (AT) to blood is a critical step in proposing rearing strategies hastening the removal of POPs from contaminated livestock. The current study aimed to determine in nonlactating ewes whether polychlorinated biphenyls (PCBs) and chlordecone are released from AT to blood along with lipids during body fat mobilization achieved through ß-agonist challenges or undernutrition. ß-Agonist challenges did not affect serum POP concentrations, whereas serum PCBs 138, 153, and 180 were readily increased in response to undernutrition. After 21 days of depuration in undernutrition, AT PCB 153 and 180 concentrations were increased concomitantly with a decrease in adipocyte volume, whereas AT chlordecone concentration was not different from that observed at the end of the well-fed contamination period. Thus, undernutrition may be of practical relevance for accelerating POP depuration unless it is combined with a strategy increasing their excretion pool.

Perinatal exposure to chlordecone and infant growth.

BACKGROUND: The intensive use of chlordecone (an organochlorine insecticide) in the French West Indies until 1993 resulted in a long-term soil and water contamination. Chlordecone has known hormonal properties and exposure through contaminated food during critical periods of development (gestation and early infancy) may affect growth. OBJECTIVES: We aimed to assess the impact of prenatal and postnatal exposure to chlordecone on the growth of children from the TIMOUN mother-child cohort. METHODS: Chlordecone was determined in cord plasma at birth (N=222) and in breast milk samples (at 3 months). Dietary chlordecone intake was estimated at 7 and 18 months, with food-frequency questionnaires and food-specific contamination data. Anthropometric measurements were taken at the 3-, 7- and 18-month visits and measurements reported in the infants' health records were noted. Structured Jenss-Bayley growth models were fitted to individual height and weight growth trajectories. The impact of exposure on growth curve parameters was estimated directly with adjusted mixed non-linear models. Weight, height and body mass index (BMI), and instantaneous height and weight growth velocities at specific ages were also analyzed relative to exposure. RESULTS: Chlordecone in cord blood was associated with a higher BMI in boys at 3 months, due to greater weight and lower height, and in girls at 8 and 18 months, mostly due to lower height. Postnatal exposure was associated with lower height, weight and BMI at 3, 8 and 18 months, particularly in girls. CONCLUSION: Chlordecone exposure may affect growth trajectories in children aged 0 to 18 months.

Ultra-trace quantification method for chlordecone in human fluids and tissues.

Chlordecone is an organochlorine pesticide (OCP) considered as a Persistent Organic Pollutant (POP) as it persists in the environment, bio-accumulates through the food web, causes adverse effects to human health and the environment and transports across international boundaries far from its sources. The atypical physico-chemical properties of chlordecone make its inclusion in classical analytical approaches non applicable. The aim of our work was to include chlordecone in a multi organochlorine residue method preventing any degradation during the analytical process and thus allowing quantification at ppt (ngkg(-1) or ngL(-1)) levels for a wide range of OCPs in breast milk, human serum and adipose tissue. After GC-HRMS vs. MS/MS and EI vs. APCI comparisons, the major improvement in terms of sensitivity was found in decreasing the length and film thickness of the gas chromatography column. Thanks to a linear correlation between relative response and quantity of chlordecone injected, LC-(ESI-)-MS/MS was finally preferred. An acetonitrile based gradient optimized on a C30 coreshell HPLC column has led to reaching limits of quantification as low as 8ngL(-1), 25pgmL(-1) and 0.2ngg(-1) fat for breast milk, serum and adipose tissue, respectively, allowing multiresidue OCP quantification at concentration levels compatible with biomonitoring purposes and pre-requisites.

Perinatal exposure to chlordecone, thyroid hormone status and neurodevelopment in infants: the Timoun cohort study in Guadeloupe (French West Indies).

BACKGROUND: Perinatal exposure to endocrine-disrupting chemicals may affect thyroid hormones homeostasis and impair brain development. Chlordecone, an organochlorine insecticide widely used in the French West Indies has known estrogenic and progestin properties, but no data is available, human or animal, on its action on thyroid hormone system. OBJECTIVES: Our aim was to evaluate the impact of perinatal exposure to chlordecone on the thyroid hormone system of a sample of infants from the Timoun mother-child cohort in Guadeloupe and their further neurodevelopment. METHODS: Chlordecone was measured in cord blood and breast milk samples. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4) were determined in child blood at 3 months (n=111). Toddlers were further assessed at 18 months using an adapted version of the Ages and Stages Questionnaire (ASQ). RESULTS: Cord chlordecone was associated with an increase in TSH in boys, whereas postnatal exposure was associated with a decrease in FT3 overall, and in FT4 among girls. Higher TSH level at 3 months was positively associated with the ASQ score of fine motor development at 18 months among boys, but TSH did not modify the association between prenatal chlordecone exposure and poorer ASQ fine motor score. CONCLUSIONS: Perinatal exposure to chlordecone may affect TSH and thyroid hormone levels at 3 months, differently according to the sex of the infant. This disruption however did not appear to intervene in the pathway between prenatal chlordecone exposure and fine motor child development.

Kinetic study of chlordecone orally given to laying hens (Gallus domesticus).

The former use of chlordecone (CLD) in the French West Indies has resulted in long-term pollution of soils. In this area, CLD may be transferred into eggs of hens reared outdoors, through soil ingestion. In order to assess this risk, a kinetic study involving the contamination of laying hens (22 weeks of age) with a diet containing 500 µg CLD kg(-1) during 42 d, followed by a depuration period of 35 d was carried out. Forty-four hens were sequentially slaughtered all over the experimental period and their liver, egg, abdominal fat and serum were collected. Two additional edible tissues, pectoral and leg muscles, were collected in hens slaughtered at the end of the contamination period. The depuration half-life of CLD in liver, egg, abdominal fat and serum was estimated at 5.0 ± 0.38 (mean ± SE), 5.5 ± 0.29, 5.3 ± 0.37 and 5.1 ± 0.66 d, respectively. CLD concentration at the end of the contamination period reached 1640 ± 274, 460 ± 41, 331 ± 23, and 213 ± 8.5 µg kg(-1) fresh matter (FM), respectively. The corresponding concentrations in pectoral and leg muscles were 119 ± 8.4, 127 ± 11 µg kg(-1) FM, respectively. The steady state carry over rate of CLD in eggs reached 43 ± 7.6%. This experiment demonstrates the preferential accumulation of CLD in liver, its significant transfer to eggs and its quite short half-life. It is concluded that raising hens on even mildly contaminated areas would lead to products exceeding the regulatory maximum residue limit of 20 µg CLD kg(-1).

Hypertensive disorders of pregnancy and gestational diabetes mellitus among French Caribbean women chronically exposed to chlordecone.

Few studies have explored the consequences of environmental exposure to organochlorine pesticides for gestational hypertension (GH), preeclampsia (PE) and gestational diabetes mellitus (GDM). Chlordecone is a persistent organochlorine pesticide that was used intensively, and almost exclusively, in the French West Indies until 1993. We investigated the impact of prenatal exposure to chlordecone on the occurrence of GDM, GH and PE by studying 779 pregnant women enrolled in a prospective mother-child cohort (Timoun Study) in Guadeloupe between 2004 and 2007. Chlordecone exposure was determined by assaying maternal plasma and information about pregnancy complications was obtained from midwives, pediatricians and hospital medical records after delivery. The risks of GH (n=65), PE (n=31) and GDM (n=71) were estimated by multiple logistic regression including potential confounders. Levels of chlordecone plasma concentration in the third (OR=0.2; 95% confidence interval (CI): 0.1, 0.5) and fourth quartiles (OR=0.3; 95% CI: 0.2, 0.7) were associated with a statistically significant decrease in the risk of GH. A log10 increase in chlordecone concentration was significantly associated with lower risk of GH (OR=0.4; 95% CI: 0.2, 0.6). No significant associations were observed between the chlordecone exposure and the risk of PE or GDM. This study suggests an inverse association between chlordecone exposure during pregnancy and GH. Further studies are required to determine the underlying mechanism, or the potential unknown confounding factors, resulting in this association.

Relative bioavailability of soil-bound chlordecone in growing lambs.

The pollution of soil with the pesticide chlordecone (CLD) is a problem for the use of agricultural surfaces even years after its use has been forbidden. Therefore, the exposure of free-ranged animals such as ruminants needs to be investigated in order to assess the risk of contamination of the food chain. Indeed, measured concentrations could be integrated in a lowered extent if the soil binding would reduce the bioavailability of the pesticide. This bioavailability of soil-bound CLD in a heavily polluted andosol has been investigated relatively of CLD given via spiked oil. Twenty-four weaned lambs were exposed to graded doses of 2, 4 or 6 µg CLD/kg body weight during 15 days via the contaminated soil in comparison to spiked oil. The concentration of this pesticide has been determined in two target tissues: blood serum and kidney fat. The relative bioavailability (RBA) corresponds to the slope ratio between the test matrix-contaminated soil- in comparison to the reference matrix oil. The RBA of the soil-bound CLD was not found to significantly differ from the reference matrix oil in lambs meaning that the pesticide ingested by grazing ruminants would not be sequestered by soil binding. Therefore, CLD from soil gets bioavailable within the intestinal level and exposure to contaminated soil has to be integrated in risk assessments.

Chlordecone exposure, length of gestation, and risk of preterm birth.

Persistent organic pollutants have not been conclusively associated with length of gestation or with preterm birth. Chlordecone is an organochlorine pesticide that has been extensively used to control the banana root borer population in the French West Indies. Data from the Timoun Mother-Child Cohort Study conducted in Guadeloupe between 2004 and 2007 were used to examine the associations of chlordecone concentrations in maternal plasma with the length of gestation and the rate preterm birth in 818 pregnant women. Data were analyzed using multivariate linear regression for length of gestation and a Cox model for preterm birth. The median plasma chlordecone concentration was 0.39 µg/L (interquartile range, 0.18-0.83). No correlation was observed with plasma concentrations of p,p'-dichlorodiphenyl dichloroethene (ρ = 0.017) or polychlorinated biphenyl 153 (ρ = -0.016), the other main organochlorine compounds detected. A 1-log10 increase in chlordecone concentration was associated with a decreased length of gestation (-0.27 weeks; 95% confidence interval: -0.50, -0.03) and an increased risk of preterm birth (60%; 95% confidence interval: 10, 130). These associations may result from the estrogen-like and progestin-like properties of chlordecone. These results are of public health relevance because of the prolonged persistence of chlordecone in the environment and the high background rate of preterm births in this population.

Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants.

Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control. Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food. Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development. This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth-cohort of Guadeloupean children. In a prospective longitudinal study conducted in Guadeloupe (Timoun mother-child cohort study), exposure to chlordecone was measured at birth from an umbilical cord blood sample (n=141) and from a breast milk sample collected at 3 months postpartum (n=75). Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire. Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores. When analyses were conducted separately for boys and girls, this effect was only observed among boys. These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development.

Chlordecone exposure and risk of prostate cancer.

PURPOSE: Determining whether environmental estrogens are associated with the risk of prostate cancer may have important implications for our general understanding of this disease. The estrogenic insecticide chlordecone was used extensively in the French West Indies, contaminating the population for more than 30 years. We analyzed the relationship between exposure to chlordecone and the risk of prostate cancer. PATIENTS AND METHODS: We investigated 623 men with prostate cancer and 671 controls. Exposure was analyzed according to case-control status, using either current plasma concentration or a cumulative exposure index based on years of exposure. We genotyped two single-nucleotide polymorphisms (rs3829125 and rs17134592) in the gene encoding chlordecone reductase. RESULTS: We found a significant increase in the risk of prostate cancer with increasing plasma chlordecone concentration (odds ratio [OR], 1.77; 95% CI, 1.21 to 2.58 for the highest tertile of values above the limit of detection [LD]; P trend = .002) and for cumulative exposure index (OR, 1.73; 95% CI, 1.04 to 2.88 for the highest quartile; P trend = .004). Stronger associations were observed among those with a positive family history of prostate cancer and among those who had lived in a Western country. The rs3829125 and rs17134592 allele variants were in complete linkage disequilibrium and were found at low frequency (0.04). Among subjects with plasma chlordecone concentrations above the LD, carriers of the allele variants had a higher risk of prostate cancer (OR, 5.23; 95% CI, 0.82 to 33.32). CONCLUSION: These findings support the hypothesis that exposure to environmental estrogens increases the risk of prostate cancer.

Pesticide exposure of pregnant women in Guadeloupe: ability of a food frequency questionnaire to estimate blood concentration of chlordecone.

CONTEXT: Chlordecone, an environmentally persistent organochlorine insecticide used intensively in banana culture in the French West Indies until 1993, has permanently polluted soils and contaminated foodstuffs. Consumption of contaminated food is the main source of exposure nowadays. We sought to identify main contributors to blood chlordecone concentration (BCC) and to validate an exposure indicator based on food intakes. MATERIAL AND METHODS: We used a food frequency questionnaire (FFQ) completed by a sample of 194 pregnant women to estimate their dietary exposure to chlordecone and compared it to blood levels. In a first approach, chlordecone daily intake was estimated as the product of daily eaten quantity of 214 foodstuffs, multiplied by their chlordecone content, and summed over all items. We then predicted individual blood chlordecone concentration with empirical weight regression models based on frequency of food consumption, and without contamination data. RESULTS: Among the 191 subjects who had BCC determination, 146 (76%) had detectable values and mean BCC was 0.86 ng/mL (range < LOD-13.2). Mean per capita dietary intake of chlordecone was estimated at 3.3 microg/day (range: 0.1-22.2). Blood chlordecone levels were significantly correlated with food exposure predicted from the empirical weight models (r=0.47, p<0.0001) and, to a lesser extent, with chlordecone intake estimated from food consumption and food contamination data (r=0.20, p=0.007). Main contributors to chlordecone exposure included seafood, root vegetables, and Cucurbitaceous. CONCLUSION: These results show that the Timoun FFQ provides valid estimates of chlordecone exposure. Estimates from empirical weight models correlated better with blood levels of chlordecone than did estimates from the dietary intake assessment.

Quantitative determination of endocrine- disrupting polychlorinated biphenyls and organochlorinated pesticides in human serum using gas chromatography with electron-capture detection and tandem mass spectrometry.

A sensitive, selective and reliable procedure was developed and validated to determine organochlorinated compounds, which have endocrine-disrupting effects, in human serum. Target compounds were selected between polychlorinated biphenyls and organochlorinated pesticides. Sample workup consisted of (1) extraction of serum with organic solvents, (2) clean-up of the organic extract using acid treatment with H(2)SO(4), (3) elution of the cleaned-up extract through a liquid column chromatographic system and (4) analysis of the fraction eluted by gas chromatography with electron capture detection (ECD) and tandem mass spectrometry (MS/MS) detection. Performance characteristics, such as linearity, sensitivity, precision, accuracy and recovery, of both chromatographic methods were studied. The proposed analytical methodology was applied to determine the target compounds in serum samples from women living in agricultural areas of Almería (Spain). The results show the advantage of MS/MS over ECD in the analysis of real human serum samples where matrix interferences can be confused with target pesticides.

Influence of dietary calcium on chlordecone-induced biochemical changes in serum of rat.

Male, Sprague-Dawley rats were treated with different (1, 10, 50, and 100 ppm) concentrations of chlordecone (Cd) in calcium-sufficient (Ca-S) or calcium-deficient (Ca-D) diet for 15 days. No significant changes in serum total proteins were observed. However, serum nonprotein nitrogen compounds (urea, uric acid, and creatinine) and glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, creatine kinase, and alkaline phosphatase were significantly increased at 50 and 100 ppm of Cd. Chlordecone induced more increase in these serum components of rats fed with Ca-D as compared to Ca-S diet. Increased serum nonprotein nitrogen compounds and enzymes indicate Cd-altered glomerular and hepatic functions.

A characterization of chlordecone pretreatment-altered pharmacokinetics in mice.

Lipophilic chlorinated hydrocarbons pose a potential health hazard to humans and animals and the toxicity of a number of these compounds has been well documented. Despite the low environmental concentrations of most of these chemicals, much of the research conducted to date has used maximally tolerated doses. Our research, conducted with low, apparently nontoxic, doses of the insecticide chlordecone (CD), showed that the administration of CD (5 mg/kg ip) to mice (C57BL/6N and DBA/2N strains) caused a time-dependent alteration in the pattern of distribution of a subsequently administered dose of [14C]CD. Livers of CD-pretreated animals contained less label than did those from controls and CD pretreatment increased amounts of label in kidney, lung, fat, and muscle. Changes did not appear to be due to an altered rate of metaboLism and analysis of total CD in tissues (unlabeled plus [14C]CD) indicated that these responses were not due to a simple redistribution phenomenon. We have termed this preexposure effect a pretreatment disposition response (PDR) and feel it may reflect an important cellular response to lipophilic compounds. CD-induced PDR is dose related, exhibits a threshold, and is saturable at a given level of induction. In addition, PDR exhibits some specificity, inasmuch as pretreating mice with CD (5 mg/kg) does not alter the distribution of subsequently administered [14C]dieldrin. The characteristics of threshold, saturability, and specificity are consistent with the premise that CD-induced PDR is a protein-mediated phenomenon.

Neurological manifestations in humans exposed to chlordecone: follow-up results.

Twenty-three workers chronically exposed to chlordecone developed overt neurologic manifestations. These included postural and intention tremor, gait difficulty and opsoclonus. Blood levels of chlordecone ranged from 2.0 to 33.0 ppm. The manifestations slowly cleared in all but one worker.