Inhibition of metabolic cooperation in Chinese hamster lung fibroblast cells (V79) in culture by various DDT-analogs

Anin vitro assay measuring inhibition of metabolic cooperation in Chinese hamster lung fibroblast cells (V79) was used to investigate the effects of DDT and five DDT analogs (dicofol, chlorobenzilate, bromopropylate, chloropropylate and fenarimol). These compounds were studied primarily because of the nongenotoxic but simultaneously carcinogenic properties of DDT and its analogs (chlorobenzilate and dicofol) and, secondly, to investigate how variations in the metabolic cooperation of hamster cells could be related to the chemical structure of the compounds. The results clearly demonstrate that all tested pesticides influenced the metabolic cooperation in a dose-dependent manner. The weak response of fenarimol suggests that sterical hindrance might influence the inhibition of metabolic cooperation.     

Bivalent bendamustine and melphalan derivatives as anticancer agents

The alkylating agents bendamustine and melphalan are currently used in the treatment of various tumoral diseases. In order to increase their antitumor potency and tumor selectivity both compounds were integrated in structure-activity relationship studies including new drug carrier systems. Here we describe the synthesis and the cytotoxicity of new bivalent bendamustine and melphalan derivatives. Two molecules each esterified with N-(2-hydroxyethyl)maleimide were connected by diamines with various chain lengths (n = 6, 7, 8, 12). It was supposed that these conjugates (5a-d, 10a-d, 11a-d) cause cytotoxic effects preferred as bivalent drug. Indeed the cytotoxicity of the new compounds increased compared to bendamustine and melphalan as determined in concentration-dependent in vitro assays using the human MCF-7 and MDA-MB-231 breast cancer cell lines.     

In vivo andIn vitro studies on synergism with anticholinesterase pesticides in the snailLymnaea acuminata

The synergistic effects of piperonyl butoxide (PB)², sulfoxide (SU), and dimethyl amino aniline (DAA) used in conjunction with two organophosphate pesticides (phorate and formothion) and two carbamate pesticides (mexacarbate and carbaryl) were examined in terms of the LC₅₀ and acetylcholinesterase (AChE) inhibition in the snailLymnaea acuminata. The three synergists reduced the LC₅₀ of phorate, formothion, mexacarbate, and carbaryl at exposure periods ranging from 24 to 144 hr. PB and SU had strong synergistic action; DAA had little effect; the highest synergistic ratio (70) was found with carbaryl and PB. The synergists enhanced thein vitro inhibition of cholinesterase caused by the pesticides; the synergistic effect onin vitro inhibition, however, was lower, compared to the change in the LC₅₀.     

Organochlorine Chemical Residues in Northern Cardinal (<Emphasis Type="Italic">Cardinalis cardinalis</Emphasis>) Eggs from Greater Washington,DC USA

Northern Cardinal eggs from six neighborhoods near Washington DC were analyzed for organochlorine pesticides and PCBs. All compounds were detected more frequently and at higher concentrations in more heavily urbanized neighborhoods. DDT (mostly as p,p?-DDE) was detected in all neighborhoods. p,p?-DDT was typically 0.5?16 ng/g (ww) in most suburban neighborhoods but was not detected (<?0.1 ng/g) in more rural areas; however, p,p?-DDT was 127?1130 ng/g in eggs from two suburban Maryland nests and comprised 65.7% of total p,p?-DDT isomers in the most contaminated sample, indicating recent exposure to un-weathered DDT. Total chlordane (sum of 5 compounds) was 2?70 ng/g; concentrations were greatest in older suburban neighborhoods. Total PCB (sum of detected congeners) was <?5?21 ng/g. Congener patterns were similar in all neighborhoods and resembled those typical of weathered mixtures. Results indicate that wildlife remains exposed to low concentrations of legacy contaminants in suburban neighborhoods and that cardinal eggs can be used to monitor localized contamination.     

Phorate and mexacarbate induced changes in enzymes of the snail,Lymnaea acuminata

The snailLymnaea acuminata, vector of the liver flukesFasciola hepatica andFasciola gigantica, was exposed to 40% and 80% LC₅₀ doses of the pesticides 12/24 mg/L phorate (O,O-diethylS-(ethylthio) methyl phosphorodithioate) and 2.5/5.0 mg/L of mexacarbate (4-dimethylamino)-3,5-dimethylphenyl methyl carbamate) for 24 or 48 hr. These pesticides, although considered to be antiacetylcholinesterase agents, inhibited alkaline phosphatase and enhanced the activity of acid phosphatase in hepatopancreas, mantle, intestine, and foot of the snail. Trypsin activity in the alimentary canal of the snail was also inhibited. Discontinuation of pesticide treatment resulted in partial recovery in mexacarbate-treated animals while in phorate-treated animals the effect of the pesticide was largely irreversible.     

Development and immunological evaluation of HLA-specific chronic myeloid leukemia polyepitope vaccine in Chinese population

Background

BCR/ABL and Wilms’ tumor 1 (WT1) are an ideal tumor associated antigens which can be used to develop a potential chronic myeloid leukemia (CML) dentritic cell (DC) vaccine. Here, we constructed a novel polyepitope vaccine which used recombinant lentiviral vector carrying BCR/ABL and WT1 genes, and determined the immunological effects of this vaccine in vitro.

Methods

The DC vaccine was constructed using lentiviral vector transduced DCs. T lymphocytes were stimulated with DC vaccine and then co-cultured in vitro with peripheral blood mononuclear cells (PBMCs) from CML or ALL patients, respectively. The cytotoxicity of proliferous cytotoxic T lymphocytes (CTLs) was determined by the LDH assay. The IFN-γ production of CTLs was detected using ELISPOT assay.

Results

We constructed an lentiviral vector encoding 50 different epitopes from BCR/ABL and WT1 antigens, and transferred it into DCs to prepare the DC vaccine successfully. The in vivo stimulation of CTLs with this DC vaccine were proved to show strong cytotoxicity and produce high level of IFN-γ.

Conclusions

The novel recombinant lentiviral polyepitope DC vaccine is a promising candidate for clinical trials and may be an effective approach for CML immunotherapy.     

Acute toxicity of dechlorinated ddt,chlordane and lindane to bluegill (Lepomis macrochirus) andDaphnia magna

Conclusions The acute toxicity of DDT and chlordane formulations was considerably reduced by nickel boridecatalyzed dechlorination. However, the reduction in toxicity was not sufficient to warrant the use of this method for the ultimate disposal of these pesticides. The dechlorination of lindane by this method appears to have potential as a chemical disposal procedure.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.This paper describes research that was completed by the senior author as partial fulfillment of the requirements for the M.A. degree, Hood College, Frederick, MD.     

Perfluorinated Compounds,Polychlorinated Biphenyls,and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas,Texas, USA

Objectives

The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362].

Methods

In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American.

Results

Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels.

Conclusion

Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.     

Organic Contaminants in the Marine Environment of Manila Bay,Philippines

Organochlorine pesticides (OCs) and polychlorobiphenyls (PCBs) were determined in sediments and oysters’ soft tissues (Cassostrea gigas) collected in selected sites of Manila Bay. Overall, the concentration levels were very low. In sediments, PCBs were the compounds present in higher concentrations, with Σ13PCB congeners averaging 0.69 ± 0.46 ng/g (dry weight), followed by ΣDDT averaging 0.53 ± 0.28 ng/g and Σchlordane with 0.26 ± 0.28 ng/g. Concentrations measured in oysters averaged 20 ± 17 ng/g (dry weight) for Σ13PCB and were higher than ΣDDT, with 9.5 ± 2.4 ng/g, and Σchlordane, with 3.8 ± 3.1 ng/g. No dissolved residues of polar compounds, such as herbicides, and organophosphorous and organochlorine pesticides were found in the bay water. In general, results showed that concentrations of organochlorine pesticide residues, such as DDT, hexachlorocyclohexane, chlordane, lindane, endosulfan, and heptachlor in sediments and oysters were low in comparison with other coastal areas in Asia, although PCB concentrations in oysters were relatively high in some zones of Manila Bay and indicative of loose control of industrial chemical waste discharges into the bay. Nevertheless, current concentrations of persistent organochlorine contaminants in sediments were under threshold effect levels (TELs) and chronic toxic effects are, thus, unlikely to generate impairment of marine biota in Manila Bay.     

Concentrations of trace elements [corrected] and organochlorines in Mutton bird (Puffinus griseus)

The Sooty Shearwater (Puffinus griseus, commonly known as Mutton bird) is a migratory wild seabird, annually harvested for food by certain native groups in New Zealand and Australia and in many parts of the world. The concentrations of 22 elements and several organochlorine pesticides [2,2-bis(chlorophenyl)-1,1,1-trichloroethane (DDT), its derivatives dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyldichloroethane (DDD), aldrin, chlordane, dicofol, lindane, and methoxychlor] in Mutton bird were determined over two consecutive years to evaluate its safety for human consumption. Twenty bird carcasses were purchased in each of 2007 and 2008 from a local source. No significant year effect (P>0.05) was found in the following nine trace elements: Al, As, Cd, Co, Cr, Cu, Ni, Pb and Se. The concentrations of Hg, Li and Na were higher (P<0.05) in 2008 samples compared to 2007. The toxic trace elements (mg/kg wet weight) in all the samples were below the maximum residual level (MRL). The concentration of Fe, Ca and Se in Mutton bird was higher than that in domestic land animal meats reported in literature. The residual organochlorine concentrations were all below the recommended MRL. Thus Mutton bird meat is high in essential nutrient elements and of low toxicological risk. Due to active use of agrochemical in New Zealand, a monitoring program for contaminants in Mutton birds is recommended.     

Organochlorine Pesticides Residues in Human Breast Milk from the Middle Governorates in Jordan in 2013/2014

One hundred samples of mother breast milk were gathered from six middle governorates and districts in Jordan in 2013/2014 to monitor Organochlorine pesticides pollutants. The results showed clearly that banned organochlorine pesticides are still detected in the monitored samples in low concentration despite banning of these persistent pollutants in Jordan since 36 years ago. However, the results indicated that 1% of the contaminated samples contained β-HCH, 5% γ-HCH, 3% p,p′-DDD, 2% heptachlor, 45% p,p′-DDE and 3% p,p′-DDT. In addition, these monitored samples had no residues of aldrin, dieldrin, α-endosulfan, β-endosulfan, HCB, o,p′-DD, o,p′-DDT and o,p′-DDE. In conclusion, there was a decline in the residues of Organochlorine pesticides, particularly DDT group members.     

Residential Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Childhood Leukemia

Background

Incidence of childhood leukemia in industrialized countries rose significantly during 1975–2004, and the reasons for the increase are not understood.

Objectives

We used carpet dust as an exposure indicator to examine the risk of childhood leukemia in relation to residential exposure to persistent organochlorine chemicals: six polychlorinated biphenyl (PCB) congeners and the pesticides α- and γ-chlordane, p,p′-DDT (dichlorodiphenyltrichloroethane), p,p′-DDE (dichlorodiphenyldichloroethylene), methoxychlor, and pentachlorophenol.

Methods

We conducted a population-based case–control study in 35 counties in northern and central California in 2001–2006. The study included 184 acute lymphocytic leukemia (ALL) cases 0–7 years of age and 212 birth certificate controls matched to cases by birth date, sex, race, and Hispanic ethnicity. We collected carpet dust samples from the room where the child spent the most time before diagnosis (similar date for controls) using a specialized vacuum.

Results

Detection of any PCB congener in the dust conferred a 2-fold increased risk of ALL [odds ratio (OR) = 1.97; 95% confidence interval (CI), 1.22–3.17]. Compared with those in the lowest quartile of total PCBs, the highest quartile was associated with about a 3-fold risk (OR = 2.78; 95% CI, 1.41–5.48), and the positive trend was significant (p = 0.017). Significant positive trends in ALL risk were apparent with increasing concentrations of PCB congeners 118, 138, and 153. We observed no significant positive associations for chlordane, DDT, DDE, methoxychlor, or pentachlorophenol. The associations with PCBs were stronger among non-Hispanic whites than among Hispanics despite similar distributions of PCB levels among controls in each racial/ethnic group.

Conclusions

Our findings suggest that PCBs, which are considered probable human carcinogens and cause perturbations of the immune system, may represent a previously unrecognized risk factor for childhood leukemia.     

Historical Trends and Chiral Signatures of Organochlorine Pesticides in Sediments of Qiandao Lake,China

This study investigated the enantiomeric and depth profiles of organochlorine pesticides (OCPs) accumulated in the sediments of Qiandao Lake, China. OCP concentrations in sediments have increased gradually since the early 1960s, when extensive OCPs application in China began. Concentrations reached maximum levels after 1992, this timing corresponds with the emerging of the “new” usage of hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethane (DDTs). In addition, the degradation of chiral OCPs were enantioselective, resulting in enriched (?)-enantiomers for α-HCH and o, p’-DDD. However, both preferential depletions of (?) enantiomers and (+) enantiomers were observed for o, p’-DDT. This outcome was indicated by enantiomer fractions (EF) values either greater or less than 0.5.     

Cytotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin on primary cultures of adult rat hepatocytes

Primary cultures of adult rat hepatocytes were used to study the cytotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were treated with a single oral dose of 5, 10 or 25Μg/kg of TCDD. At 2, 6, 10, 20, 30 days post-treatment, hepatocytes were isolated by a collagenase perfusion technique and maintained 48 hr as monolayers in serum-free medium in collagen-coated culture dishes. Uptake of ouabain was depressed in hepatocyte cultures isolated from all three doses of TCDD-treated rats. The effect was detected two days after TCDD-treatment and continued up to 30 days. The magnitude of the depression was directly related to the dose of TCDD. Hepatocyte cultures from TCDD-treated rats also showed depression in hormonally induced uptake ofα-aminoisobutyric acid (AIB) and tyrosine aminotransferase (TAT) activity at 10 and 25Μg/kg but not at 5Μg/kg. These cytotoxic effects of TCDD could be demonstrated only when TCDD was given to rats prior to isolation of hepatocytes; no toxic effects were observed when TCDD was added directly to the hepatocyte cultures. Pretreatment of rats with 1,3,6,8-tetrachlorodibenzo-p-dioxin had no effect on ouabain uptake, AIB transport, or TAT activities.     

A comparison of organochlorine pesticide residues in maternal adipose tissue,maternal blood,cord blood,and human milk from mother/infant pairs

A total of 41 samples of maternal blood, milk, subcutaneous fat and umbilical cord blood were collected from mothers giving birth by Caesarean operation at Kenyatta National Hospital in Nairobi in 1986. The samples were analyzed for organochlorine contaminants. The main contaminants found in all the samples were p,p-DDT (100%), p,p-DDE (100%), o,p-DDT (59%), dieldrin (27%), transnonachlor (15%), -HCH (12%) and lindane (2%) of all the samples analyzed. Polychlorobiphenyl (PCB) residues were not detected in any of the samples.The mean levels (mg/kg fat) of sum of DDT were 5.9 in subcutaneous fat, 4.8 in mothers milk, 2.7 in maternal serum and 1.9 in umbilical cord serum. There was a significant correlation between the levels of sum DDT in subcutaneous fat and milk fat (r=0.963), subcutaneous fat and maternal serum fat (r=0.843), and maternal serum fat and maternal milk fat (r=0.868), indicating the coherence of DDT in the body.Hexachlorocyclohexane (-HCH) was found in subcutaneous fat and milk fat with the mean levels of 0.03 and 0.26 mg/kg fat, respectively. Dieldrin detected in mothers milk and subcutaneous fat could not be quantified.     

Rotenone, paraquat, and Parkinson's disease

Background

Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.

Objectives

Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.

Methods

We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case.

Results

In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7).

Conclusions

PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.     

Agricultural use of DDT and risk of non-Hodgkin's lymphoma: pooled analysis of three case-control studies in the United States

OBJECTIVES: The objective of this pooled analysis was to examine whether exposure to DDT was associated with the risk of non-Hodgkin's lymphoma among male farmers. METHODS: Data from three case-control studies from four midwestern states in the United States (Nebraska, Iowa, Minnesota, Kansas) were pooled to carry out analyses of 993 cases and 2918 controls. Information on use of agricultural pesticides and other risk factors was based on interviews. Non-farmers (people who had never lived or worked on a farm) were used as a reference category. RESULTS: There were 161 cases and 340 controls who reported use of DDT on animals or crops, or on both, yielding an odds ratio (OR) of 1.2 (95% confidence intervals (95% CI) 1.0 to 1.6). Farmers who had used DDT for > or = 15 years had an OR of 1.5 (95% CI 1.0 to 2.3). Adjustment for respondent status and use of other pesticides resulted in slightly reduced ORs. Analyses by the number of days of use a year was limited to the Nebraska data. The most notable increase was found among farmers who used DDT for > or = 5 days a year (OR 2.6, 95% CI 1.1 to 5.9); however, additional adjustment for use of organophosphates, phenoxyacetic acids, and the individual pesticides lindane, malathion, and atrazine reduced the ORs to 1.0, 0.9, 1.1, 1.6, and 1.9 respectively. CONCLUSIONS: No strong consistent evidence was found for an association between exposure to DDT and risk of non-Hodgkin's lymphoma. It seems that the excess risk initially found may be explained by use of other pesticides.

 

     

Sixty-Year Sedimentary Record of DDTs, HCHs, CHLs and Endosulfan from Emerging Development Gulfs: A Case Study in the Beibu Gulf, South China Sea

The temporal distribution of organochlorine pesticides (OCPs) was examined in the ²¹⁰Pb dated sediment core from the Beibu Gulf, South China Sea. The total OCPs concentrations were in the range of 0.93–26.6 ng g^?1 dry weight. Dichlorodiphenyltrichloroethanes (DDTs) (0.17–24.8 ng g^?1), Hexachlorocyclohexanes (HCHs) (0.04–0.51 ng g^?1), Chlordane related compounds (CHLs) (0.22–1.72 ng g^?1) and endosulfan (n.d.–0.91 ng g^?1) were the predominant compounds. Similar to most Chinese coastal areas, the levels of DDTs in the Beibu Gulf became elevated since the early 1990s, especially since 2000 despite the ban in 1983 in China. This suggests that the concentrations of DDTs were controlled by several processes, such as land reclamation and soil runoff. The isomer ratios of (p,p′-DDE + p,p′-DDD)/p,p′-DDT, p,p′-DDT/DDTs along with construction land expansion indicated that economic activities, land reclamation, soil runoff and the use of DDT-containing antifouling paints might be responsible for the input of DDT. The ratios of α-HCH/γ-HCH (and γ-HCH/HCHs) and trans-chlordane/cis-chlordane (TC/CC) indicated fresh inputs of lindane and chlordane, respectively. In addition, CC was found to be degraded faster than TC under anaerobic conditions in sediments from the Beibu Gulf.     

Structure-Activity–Dependent Regulation of Cell Communication by Perfluorinated Fatty Acids using in Vivo and in Vitro Model Systems

Background

Perfluoroalkanoates, [e.g., perfluorooctanoate (PFOA)], are known peroxisome proliferators that induce hepatomegaly and hepatocarcinogenesis in rodents, and are classic non-genotoxic carcinogens that inhibit in vitro gap-junctional intercellular communication (GJIC). This inhibition of GJIC is known to be a function of perfluorinated carbon lengths ranging from 7 to 10.

Objectives

The aim of this study was to determine if the inhibition of GJIC by PFOA but not perfluoropentanoate (PFPeA) observed in F344 rat liver cells in vitro also occurs in F344 rats in vivo and to determine mechanisms of PFOA dysregulation of GJIC using in vitro assay systems.

Methods

We used an incision load/dye transfer technique to assess GJIC in livers of rats exposed to PFOA and PFPeA. We used in vitro assays with inhibitors of cell signaling enzymes and antioxidants known to regulate GJIC to identify which enzymes regulated PFOA-induced inhibition of GJIC.

Results

PFOA inhibited GJIC and induced hepatomegaly in rat livers, whereas PFPeA had no effect on either end point. Serum biochemistry of liver enzymes indicated no cytotoxic response to these compounds. In vitro analysis of mitogen-activated protein kinase (MAPK) indicated that PFOA, but not PFPeA, can activate the extracellular receptor kinase (ERK). Inhibition of GJIC, in vitro, by PFOA depended on the activation of both ERK and phosphatidylcholine-specific phospholipase C (PC-PLC) in the dysregulation of GJIC in an oxidative-dependent mechanism.

Conclusions

The in vitro analysis of GJIC, an epigenetic marker of tumor promoters, can also predict the in vivo activity of PFOA, which dysregulated GJIC via ERK and PC-PLC.     

Effects of phenobarbital, chlordane, and oxytetracycline on DDT excretion in rats

The effects of phenobarbital, chlordane, and oxytetracycline on DDT biliary excretion in rats were evaluated. The relationship between the increase of biliary flow induced by these drugs and the elimination of DDT was also evaluated. Phenobarbital (2.5 mg/ml) was fed to rats in their drinking water and chlordane (200 mg/kg) was added to the diet over a period of 3 days; oxytetracycline (200 mg/kg/day) was fed to rats orally for 8 days. After these treatments [14C]DDT was administered orally to anesthetized rats and then the bile was collected through cannulation of the bile duct. The data obtained show that phenobarbital and chlordane decrease zoxazolamine paralysis time and increase liver weight and biliary flow. Both drugs increase biliary excretion of [14C]DDT and decrease [14C]DDT levels in plasma; oxytetracycline increases zoxazolamine flow significantly. Oxytetracycline does not change biliary excretion of [14C]DDT but decreases the blood levels of the insecticide; and pretreatment of animals with phenobarbital, chlordane, and oxytetracycline does not significantly change [14C]DDT concentration in bile. These data demonstrate that the increased biliary excretion of DDT depends on the rate of bile elimination.