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While, dichlorodiphenyl-trichloroethane (DDT) water dispersible powder (WDP) 75% is considered as the high performance long lasting formulation for indoor residual spraying (IRS), no information is available regarding the comparative epidemiological effectiveness of the two DDT formulations when used for IRS in Indian conditions. The current study was undertaken to compare the effectiveness of IRS using DDT WDP 75% @ one g active ingredient (AI)/m 2 with that using DDT WDP 50% @ one g AI/m 2 in controlling Anopheles fluviatilis and An. culicifacies, the primary vectors of malaria in the selected endemic areas of Odisha State. Although, cone-bioassay mortality after 8 months of post spraying on DDT 75% sprayed surfaces as well as on sprayed but mud plastered surfaces was higher than DDT 50%, the six entomological parameters viz. resting density indoors and outdoors, trap density indoors, parous rate, human blood index and infection rate of An. fluviatilis and An. culicifacies did not show any statistically significant difference in reduction/ changes from pre- to post-spray period between the two DDT formulations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This work investigates the influence of drug absorption route (intestinal lymphatics vs. blood supply) on drug pharmacokinetics and tissue distribution. To achieve this aim, the pharmacokinetics and tissue distribution of model compounds [1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane, DDT; halofantrine] and lipids were assessed following intravenous delivery in lymph lipoproteins or plasma, and were found to differ significantly. For DDT, the clearance (CL) and volume of distribution (Vd ) were higher, whereas for halofantrine, CL and V(d) were lower, after entry in lymph versus plasma due, in particular, to differences in adipose tissue and liver uptake. In a recent study, halofantrine CL and V(d) were similar following entry in lymph or entry in plasma into the systemic circulation of animals predosed with lymph, whereas in the current study, predosing lymph did not influence DDT CL and V(d). For compounds such as DDT, changes to the route of absorption may thus directly impact on pharmacokinetics and tissue distribution, whereas for halofantrine factors that influence lymphatic transport may, by altering systemic lipoprotein concentrations, indirectly impact pharmacokinetics and tissue distribution. Ultimately, careful control of dosing conditions (formulation, prandial state), and thus the extent of lymphatic transport, may be important in assuring reproducible efficacy and toxicity for lymphatically transported drugs., (Copyright © 2013 Wiley Periodicals, Inc.)

This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl(4)) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl(4) are consistent with a requirement for hepatotoxicity in its carcinogenic action.

The aim of the present work was to investigate whether DDT and its metabolites are able to induce apoptosis of human peripheral blood mononuclear cells (PBMC) both in vitro and in vivo. Cells isolated from healthy individuals were incubated in the presence of increasing concentrations of p'p-DDT, p'p-DDE, or p'p-DDD (0-150 microg/mL) for different intervals. Apoptosis was then determined by flow cytometry (DNA cell content analysis) and fluorescence microscopy (Hoechst staining). A significant level of apoptosis was induced by DDT, DDD, and DDE at 80 microg/mL compared to controls, reaching a maximum effect at 100 microg/mL. We began to detect apoptosis at 12h, with a maximum effect at 24h of incubation. These results were confirmed using the TUNEL assay in cells treated with the three compounds tested as well as with o'p-DDT at 100 microg/mL and 24h of incubation. Our data demonstrate that DDT and its metabolites are able to induce apoptosis of human PBMC in vitro. Therefore, we performed a preliminary study in children exposed to this insecticide. When compared to a control population, the exposed children had higher levels of DDT, DDD, and DDE in blood and also had a higher frequency of apoptosis. In the exposed children, a weak positive association was found between the frequency of apoptosis and the exposure to DDT and DDE. Our results showed that more studies are needed in people exposed to DDT, as apoptosis may cause serious public health effects such as immunosuppression.

In this study, DDT-induced DNA damage on blood cells was analyzed both in vitro and in vivo. Peripheral blood mononuclear cells (PBMC) were isolated from healthy donors and incubated in the presence of three different concentrations (40, 80, and 100 microg/mL) of p,p'-DDT, p,p'-DDE, and p,p'-DDD at three different treatment times (24, 48, and 72 h). Then, DNA damage was assessed by the single-cell electrophoresis assay (comet assay) as well as by flow cytometry detection of hypodiploid cells (DNA content assay). All compounds induced significant DNA damage as shown by the comet assay. Accordingly, cells exposed to DDT, DDE, and DDD showed a significant increase in the percentage of hypodiploid cells compared with untreated PBMC. In agreement with the in vitro data, a significant correlation between blood levels of DDT, DDD, and DDE and DNA damage (comet assay) was found in women with different amounts of environmental exposure. This association remained significant after controlling for nutritional status, smoking habits, alcohol ingestion, and reported exposure to other pesticides. Although the precise biological importance remains to be explained, our results strongly suggest that DDT and its metabolites are able to induce DNA damage in PBMC both in vitro and in vivo.

There are concerns about possible combination effects of environmental chemicals with oestrogenic activity and their implications for human health. Such chemicals are present in complex mixtures in our environment. A number of studies searching for possible synergistic interactions between xenoestrogens have appeared in the literature. However, in these studies no account was taken of established concepts and methods for analysing combination effects. In the present review, we highlight conceptual issues which may be useful for a sound analysis of the effects of mixtures of xenoestrogens. We find that much published work suffers from an undue focus on measuring effects of mixtures at only one dose level. Assessments of combination effects are frequently complicated by a lack of information on dose-response relationships. Some studies which purportedly show absence of synergy have in fact overlooked synergisms.

Rats treated with increasing doses of pp'-DDT (60, 100 and 180 mg/kg body wt.) i.p., for 24 h, showed a dose-independent increase in liver cytochrome P450 levels, together with an increase in lipid peroxidation, measured as production of thiobarbituric acid reactants. This oxidant condition elicited in the liver by DDT was not accompanied by any change in the activity of NADPH-cytochrome c reductase or in the rate of superoxide anion generation by liver microsomal fraction. The activities of superoxide dismutase and glutathione peroxidase were found to be increased in the higher dose DDT-treated rats, without any change in those from catalase and glutathione reductase. The results presented showed an oxidant condition in the liver elicited by DDT treatment of rats, without any adequate hypothesis proposed to explain these data.

We have recently reported that DDT and the pyrethroid bioallethrin cause similar changes in the brain muscarinic cholinergic receptors (MAChR) and behavioural disturbances in the neonatal and adult mouse when given to neonatal mice during the peak of rapid brain growth. In the present study the interaction between neonatal and adult exposure to DDT and bioallethrin, respectively, is explored. Ten-day-old NMRI mice received a single low oral dose of DDT (0.5 mg/kg body wt). At adult age (5 months) the mice received bioallethrin 0.7 mg/kg body wt./day per os for 7 days. Mice used as controls received a 20% fat emulsion vehicle. The spontaneous behavioural tests revealed significant differences, both in mice treated neonatally with DDT and receiving bioallethrin as adults and in mice receiving the vehicle as neonates and bioallethrin as adults, compared with their corresponding controls. However, the behavioural changes developed in mutually opposite directions. Significant changes in MAChR, assayed in the P2 fraction of the cerebral cortex by using the muscarinic antagonist, quinuclidinyl benzilate ([3H]QNB) and agonist carbachol, was only observed in animals receiving DDT as neonates and bioallethrin as adults. The present study indicates an increased susceptibility in the cholinergic muscarinic receptors and a different behaviour reaction in animals already exposed to DDT (at a physiologically relevant dose), when again exposed to a similar neurotoxic agent as adults.

Either a single oral dose of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl) ethane (DDT), 150 mg/kg body weight or a long-term chronic dose of the pesticide, 10 mg/kg body weight daily for 100 days was administered to rhesus monkeys and the level of various lipid classes was studied in the brain. A significant decrease was observed in total lipid, unesterified cholesterol and phospholipid (PL) level. Individual PL fractions showed a generalized pattern of reduction, so also did the cholesterol (chol)/PL ratio. Sphingomyelin (SM) registered a significant increase, while no significant alteration was observed in the brain galactolipid and ganglioside level. Lipid lowering effect of DDT was more pronounced in the chronic group. Lipids associated with the myelin sheath were found to be more resistant to pesticide injury, while cholesterol and PL metabolism were more affected.

Four-week old broiler chickens were fed rations with varying levels of technical grade DDT for a 4-week period. DDT and metabolite concentrations were measured in adrenal, liver, and brain. Accumulations per gram of tissue were greatest in the adrenals, followed by those in the liver, then in the brain. All birds fed 2700 p.p.m. of DDT died with 12 days after beginning feeding, and moderate signs of toxicity, such as ataxia and trembling, appeared in those fed 900 p.p.m. Although both DDT metabolites, p,p'-DDE and p,p'-DDD, were found in the tissues, the higher levels of the former indicated that the aerobic conversion of DDE occurs more readily than the anaerobic conversion. Significant quantities of o,p'-DDT appear only in tissues of birds fed high levels of the technical grade DDT.