Effects of maternal diet and environmental exposure to organochlorine pesticides on newborn weight in Southern Spain.

An appropriate eating pattern is essential during childbearing years and pregnancy to ensure a healthy pregnancy and newborn. Our group developed a Mediterranean Diet Score for Pregnancy (MDS-P) based on the MD and the specific need of pregnant women for Fe, Ca, and folic acid. Humans are daily exposed to endocrine disruptors, which may alter body weight and hormone system regulation. This study analyzed the relationship of maternal diet and in utero exposure to organochlorine pesticides (OCPs) with newborn weight in mothers and newborns from Southern Spain. Higher MDS-P score, folic acid supplementation, and greater in utero exposure to endosulfan-diol and endosulfan-1 were related to higher newborn weight. MDS-P score was not associated with maternal weight gain during pregnancy (above or below 12 Kg). Residues from one or more OCPs were detected in 96.5% of umbilical cord serum samples from 320 newborns. The most frequent residues were endosulfans (96.5%). The presence of endosulfan-diol, endosulfan-I, p-p´DDT, folic acid supplementation, and a higher MDS-P (>8) were predictive factors for newborn overweight (>3500 g). Conversely, smoking during pregnancy, shorter gestation time (32-36 vs. 37-39 weeks), and lesser maternal weight gain during pregnancy predicted lower newborn weight (<2500 g). These results indicate prenatal exposure to OCPs in Southern Spain and its possible impact on the weight of healthy full-term newborns. Further studies are warranted to interpret the consequences of this exposure and identify preventive measures. Adherence to the MD and folic acid supplementation during pregnancy emerged as predictive factors for overweight in newborns.

Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide.

Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP and Cl-HEPP) with two seizure models, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was examined via the rotarod test. With in silico methods, binding was probed on possible protein targets-GABAA receptors and the sodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6, 87.1, and 62.0 mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5 mg/kg. The HEPP-induced neurotoxic effect, which occurred at twice the ED50 against MES (p < 0.05), did not occur with F-HEPP or Cl-HEPP. Docking studies revealed that all tested ligands bound to GABAA receptors on a site near to the benzodiazepine binding site. However, on the sodium channel open pore Nav1.2, R-HEPP had interactions similar to those reported for phenytoin, while its enantiomer and the ligands F-HEPP and Cl-HEPP reached a site that could disrupt the passage of sodium. Our results show that, as anticonvulsant agents, parahalogen substituted compounds have an advantageous pharmacotoxicological profile compared to their precursor.

Occupational exposure to chlorinated and petroleum solvents and mycosis fungoides.

OBJECTIVE: To evaluate the potential association between occupational exposure to chlorinated and petroleum solvents and mycosis fungoides (MF). METHODS: A questionnaire on lifetime job history was administered to 100 patients diagnosed with MF and 2846 controls. Odds ratios (ORs) were calculated as the measure of the association between exposure to each specific solvent and MF. RESULTS: In the total sample and in men, cases and controls did not differ in relation to exposure to any of the solvents studied. In women, an association with MF was seen for the highest level of estimated exposure to perchloroethylene (OR = 11.38; 95% confidence interval: 1.04 to 124.85) and for exposure less than the median to kerosene/fuel/gasoil (OR = 8.53; 95% confidence interval: 1.11 to 65.62). CONCLUSIONS: These results do not provide conclusive evidence that exposure to solvents may increase risk of MF because they were not found in men.

Maternal occupational exposure to organic solvents during early pregnancy and risks of neural tube defects and orofacial clefts.

OBJECTIVES: Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs). METHODS: Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking. RESULTS: The prevalence of exposure to any solvent among mothers of NTD cases (n = 511), OFC cases (n = 1163) and controls (n = 2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR = 1.96, CI 1.34 to 2.87), especially spina bifida (OR = 2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data. CONCLUSIONS: The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.

Organochlorine compounds, iodine intake, and thyroid hormone levels during pregnancy.

The effect of organochlorine compounds (OCs) on thyroid function, as well as the potential confounding effect of iodine intake, was studied in a large sample of pregnant women from two population-based cohort studies in Sabadell (n = 520) and Gipuzkoa (n = 570), Spain. Thyroid hormones (free T4 and total T3), thyrotropin, and polychlorinated biphenyls (PCB congeners 118, 138, 153, and 180), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), dichlorodiphenyl dichloroethylene (p'p'-DDE) and dichlorodiphenyl richloroethane (p'p-DDT) were measured in serum samples collected at first trimester of pregnancy. Urinary iodine concentration (UIC) was measured and iodine intake from diet, iodized salt, and supplements were estimated from a food frequency questionnaire. Levels of HCB and PCBs congeners 180, 153, and 138 were related to lowe rtotal T3 levels (adjusted coefficient (SE): -4.0(1.1), -6.1(1.6), -5.5(1.6), and 3.8(1.4), respectively) and higher free T4 levels (adjusted coefficient (SE): 0.013(0.05), 0.017(0.007), 0.016(0.007), and 0.007(0.006), respectively). These associations were homogeneous in both cohorts, especially for PCBs and total T3 (p-value forthe interaction between cohorts >0.8). Iodine intake and UIC did not affect the association between OCs and thyroid hormones. Our results indicate that exposure to OCs during pregnancy can alter TH levels.

Photocontact dermatitis and chloracne: two major occupational and environmental skin diseases induced by different actions of halogenated chemicals.

Among occupational and environmental disorders, contact or photocontact dermatitis and an acneiform eruption are two major skin disorders. Photocontact dermatitis was historically caused by various halogenated salicylanilides, while the acne is induced by halogenated aromatic hydrocarbons and thus called chloracne. Therefore, it should be noted that halogenated chemical compounds are important causative agents in the occupational and environmental medicine. In photocontact dermatitis, photoconjugation of epidermal cells with a photohaptenic halogenated chemical is the initial step. Langerhans cells serve as antigen-presenting cells and T cells sensitized by photoantigen-bearing Langerhans cells induce this photosensitivity. On the other hand, in chloracne, halogeneted hydrocarbons render keratinocytes of the outer root sheath and sebaceous duct hyperplastic. The dilated infundibulum of most hair follicles is then filled with comedone that consist of many accumulated layers of keratinized cells and sebum. Therefore, halogenated chemicals exhibit different actions, i.e. the induction of an immunologic consequence and the modulation of keratinocyte biology. These two conditions also provide good experimental models for investigating dermatology.

Exploring environmental causes of altered ras effects: fragmentation plus integration?

Mutations in ras genes are the most common abnormality of oncogenes in human cancer and a major example of activation by point mutation. Experimental and epidemiological studies support the notion that Ki-ras activation and expression may be chemically related. We discuss the potential role of several environmental compounds in the induction or promotion of ras mutations in humans, with a focus on exocrine pancreatic cancer, the human tumor with the highest prevalence at diagnosis of Ki-ras mutations. Organochlorine compounds, organic solvents, and coffee compounds may play an indirect role in causing Ki-ras mutations, rather than as direct inducers of the mutations. Although for some organochlorine compounds the induction of point mutations in ras oncogenes cannot be excluded, it seems more likely that the effects of these compounds are mediated through nongenomic or indirectly genotoxic mechanisms of action. Organic solvents also may act via enzymatic induction of ras mutagens or by providing a proliferation advantage to ras-mutated cell clones. In exocrine pancreatic cancer, caffeine, other coffee compounds, or other factors with which coffee drinking is associated could modulate Ki-ras activation by interfering with DNA repair, cell-cycle checkpoints, and apoptosis. Asbestos, cigarette smoking, and some dietary factors also may be involved in the initiation or the promotion of Ki-ras mutations in lung and colon cancers. Further development of the mechanistic scenarios proposed here could contribute to a meaningful integration of biological, clinical, and environmental knowledge on the causes of altered ras effects.

The Inuit diet. Fatty acids and antioxidants, their role in ischemic heart disease, and exposure to organochlorines and heavy metals. An international study.

Traditional food is culturally, economically and nutritionally important for the Greenlandic Inuit people. In the 1970s the preventive effect of marine fat on cardiovascular disease, thrombosis and atherosclerosis was described. The low incidence of ischemic heart disease among Greenlanders has been related to the high intake of marine food. Since 1990 routine autopsies have taken place in two towns in Greenland, Nuuk and Ilulissat. The autopsies represent 26% of the total number of deaths in these two towns. Samples have been collected from 104 autopsies. International cooperative studies have analysed specimens in relation to ischemic heart disease as a benefit related to diet, as well as the level of heavy metals and organochlorine in organs as a risk related to diet. High amounts of mono-unsaturated and Omega-3 poly-unsaturated fatty acid were found in adipose tissue. Liver analyses of selenium have confirmed the expected high intake among Greenlanders. Reduced atherosclerotic lesions were found in the coronary arteries. Blood pressure levels calculated from renovascholopathia of hypertension indicate prevailing levels similar to those in industrialized countries. Some factors in Greenland may be protecting the coronary arteries, thereby of setting the expected effect of hypertension. The level of methyl mercury in organs is generally high. PCB concentrations found in organs of Greenlanders are higher than among other populations. Health and risk effects of the traditional foods need further investigation.

Occupational exposure to hydrocarbons and chronic pancreatitis: a case-referent study.

OBJECTIVES: To investigate the hypothesis that hydrocarbon exposure is a risk factor for chronic pancreatitis. METHODS: 102 cases of chronic pancreatitis and 204 age and sex matched referents were interviewed about their occupational histories, alcohol and cigarette consumption, and diet. Exposure to hydrocarbons was inferred from interview responses by four assessors who were blind to disease state, and these data were then summarised by a cumulative hydrocarbon exposure (CHE) score. RESULTS: After adjustment for alcohol, cigarettes, dietary antioxidants, and social class, odds ratios for low CHE scores were 1.20 (90% CI: 0.62-2.35) and 2.67 (90% CI: 1.22-5.87) for high scores. A test for trend with level of exposure among only those who had exposure scores > 0 gave p = 0.09. Analysis by type of hydrocarbon was limited to four exposures for each of which there were at least 20 exposed patients. The adjusted OR for paint solvents (any level) was 0.96 (90% CI: 0.48-1.93); for diesel exhaust fumes OR = 2.66 (90% CI: 1.05-6.73); for petrochemicals OR = 1.82 (90% CI: 0.80-4.11); and for chlorinated solvents OR = 1.49 (90% CI: 0.58-3.81). CONCLUSIONS: These results support the original hypothesis. Further studies are needed to confirm or refute the findings here and to clarify the types of hydrocarbon involved.