Neurological Impacts

Maria-Jose Lopez-Espinosa, Esther Vizcaino, Mario Murcia, Sabrina Llop, Mercedes Espada, Vicente Seco, Alfredo Marco, Marisa Rebagliato, Joan O. Grimalt and Ferran Ballester. Association between thyroid hormone levels and 4,4'-DDE concentrations in pregnant women (Valencia, Spain). Environmental Research Volume 109 Issue 4, May 2009

Panna Summary: New evidence published in the May 2009 suggests that women’s exposure to DDE in early pregnancy is linked with changes in thyroid hormone levels, which in turn affects fetal brain development. DDE is a breakdown product of the persistent pesticide DDT. In May 2009, the UN and World Health Organization announced their commitment to reduce DDT use by 30% by 2014, and to eliminate it within the 2020s. The Global Environment Facility committed $40 million to 10 projects in 40 countries for sustainable, safe malaria solutions that end reliance on DDT.

Abstract: Introduction: Several epidemiological studies have reported that some organochlorine compounds (OCs), such as polychlorobiphenyls (PCBs) and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4′-DDE), may alter thyroid function. Objective: The aim of the present study was to investigate the association of maternal serum OC concentrations of 4,4′-DDE and the sum of seven PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) with thyroid hormone (TH) status. Methods: We measured OC concentrations in 157 maternal serum samples at 12 weeks of pregnancy in a cohort from Valencia (Spain). Thyroid-stimulating hormone (TSH), total triiodothyronine (TT₃), and free thyroxine (FT₄) were measured as biomarkers of thyroid function in the same samples. Linear and logistic regression analyses were performed between OCs and TH levels, and variables were log transformed. Results: Mothers with higher levels of 4,4′-DDE had higher odds of having TSH levels >2.5 mIU/L (OR=2.53; 95% CI=1.36; 4.73; p=0.004), and we found a significant negative association between serum 4,4′-DDE concentrations and FT₄ levels (β=−0.03; 95% CI=−0.05; 0.00; p=0.050) after adjustment for covariates and total lipids. No association was found between sum of PCBs and TH levels. Conclusion: Serum concentrations of 4,4′-DDE were associated with increased TSH and reduced FT₄ but not TT₃ levels. Our results suggest that some environmental chemicals may interfere with the thyroid system of pregnant women. The major role that maternal THs may play in fetal neurodevelopment makes these findings especially relevant.

Eskenazi B, Marks AR, Bradman A, Fenster L, Johnson C, Barr DB,Jewell NP. In Utero Exposure to Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and Neurodevelopment among Young Mexican American Children. Pediatrics 2006 118: 233-24.

PANNA Summary: This study examines the amounts of DDT and DDE inmother’s serum after delivery, and looks for associations between theselevels and the infants’ development using a standard development scale.The results show a relationship between lower psychomotor development scores and increased DDT in the mothers’ serum. The population studied was Mexican American farm-workers and their children in California.

Abstract: Objective: We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexicanfarm-workers’ children in California.

Methods: Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p_-DDT, o,p_-DDT, andp,p_-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months.

Results: We found a _2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p_-DDT levels at 6 and 12 months (but not 24 months) and p,p_-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p-DDT and o,p-DDTat 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure,breastfeeding was usually associated positively with Bayley scalescores.

Conclusions:Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weighits benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment. 

Ribas-Fito N, Torrent M, Carrizo D, Munoz-Ortiz L, Julvez, J,Grimalt, JO, Sunyer, J. In Utero Exposure to Background Concentrations of DDT and Cognitive Functioning among Preschoolers. American Journal of Epidemiology 2006 164(10): 955-962

PANNA Summary: Exposure to DDT occurs both in utero and because of its lipophilicity, via breastfeeding. While animal studies have indicated effects on brain growth due to DDT exposure, neurodevelopment in humanis less documented. A study in 2005 reported higher concentrations ofDDE in newborns in Menorca, Spain, than in the Ribera d’Ebre cohort. This study is a follow up to the previous 2005 study to assess the association of cord serum levels of DDE and DDT with neurodevelopment at age 4 years. The results indicated that prenatal exposure to low level, concentrations of DDT and DDE at birth is associated with a decrease in verbal, memory, and quantitative and perceptual performance skills among preschoolers. Hence, the author suggests that even though DDT is considered to be useful in malarial control, the evidence of its adverse effects on health requires for appropriate research on its benefits versus its risks.

Abstract: p,p'-DDT (bis[p-chlorophenyl]-1,1,1-trichloroethane) is a persistent organochlorine compound that has been used worldwide as an insecticide. The authors evaluated the association of cord serum levels of DDT and its metabolite, 2, 2-bis (p-chlorophenyl)-1,1-dichloroethylene (DDE), with neurodevelopment at age 4 years. Two birth cohorts in Ribera d'Ebre and Menorca (Spain) were recruited between 1997 and 1999 (n=475). Infants were assessed at age 4 years by using the McCarthy Scales of Children's Abilities. Organochlorine compounds were measured in cord serum. Children's diet and parental sociodemographic information was obtained through questionnaire.Results showed that DDT cord serum concentration at birth was inversely associated with verbal, memory, quantitative, and perceptual-performance skills at age 4 years. Children whose DDT concentrations in cord serum were >0.20 ng/ml had mean decreases of 7.86 (standard error, 3.21) points in the verbal scale and 10.86(standard error, 4.33) points in the memory scale when compared with children whose concentrations were <0.05 ng/ml. These associations were stronger among girls. Prenatal exposure to background, low-level concentrations of DDT was associated with a decrease in preschoolers' cognitive skills. These results should be considered when evaluating the risk and benefits of spraying DDT during antimalaria and other disease-vector campaigns. (Dr. Nu´ ria Ribas-Fito´, Respiratory and Environmental Health Research Unit, IMIM, C. Doctor Aiguader 80, 08003 Barcelona, Catalonia, Spain (e-mail: nribas@imim.es)

Sinha C, Seth K, Islam F, Chaturvedi RK, Shukla S, Mathur N,Srivastava N, Agrawal AK. Behavioral and neurochemical effects inducedby pyrethroid-based mosquito repellent exposure in rat off springs during prenatal and early postnatal period. Neurotoxicol Teratol. 20064: 472-81.

PANNA Summary: Studies have shown that newborn babies, pregnant and lactating mothers are more prone to toxics when exposed to pyrethroids used as mosquito repellants since they stay for longer durations insidethe house. This pilot study found that prenatal, postnatal and perinatal exposure to pyrethroid-based Mosquito repellants could alter blood brain barrier permeability. Developing Central Nervous System hasbeen considered to be vulnerable to oxidative damage brain region as compared to other brain regions. The rat pups exposed to mosquito repellants clearly indicated significant involvement of the hippocampus. Overall, the study claims to stress on the effect of pyerethroid based repellants on the neurochemical and behavioral effects and implies that pregnant women and infants may be greatlyoffset by the benefits of the protection of repellants if the result on rats are indicative of their effects.

Abstract: Synthetic pyrethroids, besides their use in agriculture,are prevalently used in our houses as mosquito repellent (MR) in the form of aerosol, mats, coils and liquid vaporizers. Inhalation of fumes of the MR/liquid vaporizers may get entry into the brain by breaching the developing blood-brain barrier, hence deleterious to developing nervous system and can lead to long-term functional deficits. In the present study the consequence of MR exposure has further been investigated at various stages of development, evaluating free radical mediated effect pertinent to neurobehavioral and neurochemical functioning. Rat pups were exposed to pyrethroid-based MR (allethrin3.6% w/v, 8 h/day through inhalation) during prenatal (GD1-20),postnatal (PND1-30) and perinatal (GD1-PND30) period of development and assessments were made on PND31. We observed significant oxidative stress, where an increase in lipid peroxidation and a decrease in antioxidants, glutathione, superoxide dismutase and catalase in various brain areas (cerebellum, corpus striatum, frontal cortex andhippocampus) were evident at all the exposure schedules. The hippocampus was the most affected region and further exhibited altered cholinergic functioning in the form of significant decrease in cholinergic (muscarinic) receptor binding (prenatal 32%, postnatal 35%,perinatal 38%) and inhibition in acetylcholinesterase activity (prenatal 20%, postnatal 31% and perinatal 33%). The neurochemical changes were found to accompany decrease in learning and memory performance in exposed rats, the function governed by hippocampus. The result suggests that pyrethroid-based MR inhalation during early developmental period may have adverse effect on developing nervous system causing cholinergic dysfunction leading to learning and memory deficit. (Developmental Toxicology Division, Industrial ToxicologyResearch Centre, Post Box-80, M.G. Marg Lucknow 226001, India. E-mailaddress: aka33@rediffmail.com (A.K. Agrawal)