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Background: The prevalence of obesity is increasing in all countries, becoming a substantial public health concern worldwide. Increasing evidence has associated obesity with persistent pollutants such as the pesticide DDT and its metabolite p,p′-DDE. Objectives: Our objective was to systematically review the literature on the association between exposure to the pesticide DDT and its metabolites and obesity to develop hazard identification conclusions. Methods: We applied a systematic review-based strategy to identify and integrate evidence from epidemiological, in vivo, and in vitro studies. The evidence from prospective epidemiological studies was quantitatively synthesized by meta-analysis. We rated the body of evidence and integrated the streams of evidence to systematically develop hazard identification conclusions. Results: We identified seven epidemiological studies reporting prospective associations between exposure to p,p′-DDE and adiposity assessed by body mass index (BMI) z-score. The results from the meta-analysis revealed positive associations between exposure to p,p′-DDE and BMI z-score (β=0.13 BMI z-score (95% CI: 0.01, 0.25) per log increase of p,p′-DDE). Two studies constituted the primary in vivo evidence. Both studies reported positive associations between exposure to p,p′-DDT and increased adiposity in rodents. We identified 19 in vivo studies and 7 in vitro studies that supported the biological plausibility of the obesogenic effects of p,p′-DDT and p,p′-DDE. Conclusions: We classified p,p′-DDT and p,p′-DDE as “presumed” to be obesogenic for humans, based on a moderate level of primary human evidence, a moderate level of primary in vivo evidence, and a moderate level of supporting evidence from in vivo and in vitro studies. https://doi.org/10.1289/EHP527

In this study, the levels of DDT and its metabolite residues were determined in chewable parts of Catha edulis plants grown in the southern part of Ethiopia. The levels of p,p'-DDT and p,p'-DDE were found to be in the range of 10.8-19.7 and 3.5-18.6 μg/kg, respectively. These data revealed that the residue being detected is from recent applications. The estimated daily intake of total DDT from C. edulis consumption was calculated to be in the range between 0.0278 and 0.0747 μg/kg, which is significantly lower than the FAO/WHO guideline. However, this may not guarantee safety, as the application of DDT extends to vegetables as well. Even though the use of DDT was banned in Ethiopia for agriculture purposes, detectable levels are still being observed. The results of the study necessitate the need for awareness creation among the people in the community.

The long term use of many insecticides is continually threatened by the ability of insects to evolve resistance mechanisms that render the chemicals ineffective. Such resistance poses a serious threat to insect pest control both in the UK and worldwide. Resistance may result from either an increase in the ability of the insect to detoxify the insecticide or by changes in the target protein with which the insecticide interacts. DDT, the pyrethrins and the synthetic pyrethroids (the latter currently accounting for around 17% of the world insecticide market), act on the voltage-gated sodium channel proteins found in insect nerve cell membranes. The correct functioning of these channels is essential for normal transmission of nerve impulses and this process is disrupted by binding of the insecticides, leading to paralysis and eventual death. Some insect pest populations have evolved modifications of the sodium channel protein which prevent the binding of the insecticide and result in the insect developing resistance. Here we review some of the work (done at Rothamsted Research and elsewhere) that has led to the identification of specific residues on the sodium channel that may constitute the DDT and pyrethroid binding sites.

The Single Organism (SO) model was developed to investigate the influence of temporal dynamics of aquatic organism properties on their exposure to organic chemicals in water. SO was then integrated with an existing dynamic surface-water model (DynA), to form the coupled water-bioaccumulation model EcoDynA. In order to evaluate the model performance, the results produced by EcoDynA were compared to the p,p'-DDT concentrations measured in specimens of whitefish of different age and sex caught in Lake Maggiore after the discovery of a DDT spill. The comparison showed a good agreement. Other satisfying results were obtained comparing model results with p,p'-DDT concentration values measured in another species of whitefish which were available in the literature. A preliminary sensitivity analysis confirmed that accounting for dynamics of parameters such as organism lipid fraction and feeding rate is necessary to obtain accurate exposure predictions.

Over the past few decades significant progress has been made in research on DDT degradation in the environment. This review is an update of some of the recent studies on the degradation and biodegradation pathways of DDT and its metabolites, particularly in soils. The latest reports on human toxicity shows that DDT intake is still occurring even in countries that banned its use decades ago. Ageing, sequestration and formation of toxic metabolites during the degradation processes pose environmental challenges and result in difficulties in bioremediation of DDT contaminated soils. Degradation enhancement strategies such as the addition of chelators, low molecular organic acids, co-solvent washing and the use of sodium and seaweeds as ameliorant have been studied to accelerate degradation. This review describes and discusses the recent challenges and degradation enhancement strategies for DDT degradation by potentially cost effective procedures based on bioremediation. Refereed/Peer-reviewed

(1999). Biochemical and Molecular Basis of Pesticide Degradation by Microorganisms. Critical Reviews in Biotechnology: Vol. 19, No. 3, pp. 197-225.

14C-p,p′-DDT was taken up from sea water by nonfeeding marine copepods held at 6 C for 8 wk. Calanus spp. reached an equilibrium DDT level of 50–100 ppm (dry weight) after 3–4 wk exposure in an initial water concentration of [Formula: see text]. No metabolites of p,p′-DDT could be detected during this period.

Groups of 5 or 10 Rainbow trout fry ( Salmo gairdnerii ) weighing around 1 g were injected im with 14 C-labeled 2,2,bis( p -chlorophenyl)-1,1,1-trichloroethane ( p,p′ -DDT); 2,2,bis( p -chlorophenyl)-1,1-dichloroethylene ( p,p′ -DDE); 2,2,bis-( p -chlorophenyl)-1,1-dichloroethane ( p,p′ -DDD); 2,2,bis( p -chlorophenyl)-1-chloroethane ( p,p′ -DDMS); 1,1-bis( p -chlorophenyl)ethylene ( p,p′ -DDNU); 2,2,bis( p -chlorophenyl)-1-chloroethylene ( p,p′ -DDMU); 2,2,-bis( p -chlorophenyl)ethanol ( p,p′ -DDOH); p -dichlorobenzophenone ( p,p′ -DBP); p -dichlorobenzhydrol ( p,p′ -DBH); or bis( p _chlorophenyl) acetic acid ( p,p′ -DDA). At intervals of 24 hr and 3 weeks after injection (except in the case of the p,p′ -[ 14 C]DDOH- and p,p′ -[ 14 C]DDA-injected groups, where only 24-hr samples were taken), the fish were killed, extracted individually, and analyzed for p,p′ -DDT metabolites. Their water was also analyzed 24 hr after injection. p,p′ -[ 14 C]DDT was converted to p,p′ -DDE and, to a lesser extent, p,p′ -DDD. p,p′ -[ 14 C]DDD was converted to a limited extent to p,p′ -DDMU, and p,p′ -[ 14 C]DDMS was similarly dehydrochlorinated to p,p′ -DDNU. p,p′ -[ 14 C]DBH and p,p′ -[ 14 C]DBP were interconverted to some extent, and p,p′ -[ 14 C]DDA was converted to p,p′ -DBP. p,p′ -[ 14 C]DDOH was apparently converted to p,p′ -DBP in one experiment, but a second exposure did not confirm this. None of the dehydrochlorination products ( p,p′ -[ 14 C]DDE, p,p′ -[ 14 C]DDMU, and p,p′ -[ 14 C]DDNU) was degraded and p,p′ -DDMU therefore appears to be one of the end products of DDT metabolism by trout.

DDT metabolism in Phlebotomus papatasi (Scopoli) was investigated and compared to that in DDT-resistant and susceptible strains of Culex quinquefasciatus Say and Anopheles gambiae Giles with the objective of establishing baselines for sandfly studies. P. papatasi produced eight metabolites of DDT, with DDE predominating, as in the two mosquito species. Both oxidases and glutathione transferases were found to be involved in DDT metabolism in insecticide-susceptible adults of P. papatasi. The activity level of glutathione transferases and the reduced and oxidized difference spectra of cytochrome P-450 were measured spectrophotometrically. The level of glutathione transferase activity in P. papatasi was lower than that in susceptible C. quinquefasciatus adults when expressed in terms of the activity per milligram of soluble protein but, in contrast, the cytochrome P-450 was slightly higher in both the reduced and oxidized states.

The column, thin-layer, gas-liquid and liquid chromatographic, the combined liquid and gas-liquid chromatographic-mass spectroscopic techniques, as well as the biological and toxicological aspects of DDT and its metabolites have been reviewed Primary focus was placed on their utility, ecological distribution, and toxicity, as well as diverse techniques for their separation from polychlorimated biphenyls and other chlorinated pesticides and subsequent analysis.

DDT orally given to rats is converted into DDD by reductive dechlorination in the liver within 30 min. 6 h after a single application of 10 mg DDT per rat a quantity of 60 mg DDD/kg was indicated in the liver. DDT is stored in the adrenal glands; in the other organs an equilibrium comes up obviously, even with further application. The quantitative ratios are reported. Information on the experimental details of DDT determination and--anticipatory to the following publications--on the analysis of the most relevant metabolites is given.

Eighty-four Single-Comb While Leghorn laying hens housed individually in laying cages were fed rations containing less than 0.1 p.p.m. of dieldrin, DDT, heptachlor and mirex individually or in combination for 7 days and in combination for 15 weeks. DDT residues in egg yolk reached 0.043 p.p.m. by 7 days when fed in combination with the other pesticides. None of the residues were above FDA action level at 7 days and all had declined to below trace levels by 8 weeks after termination of pesticide feeding. Residues in eggs from hens fed all four pesticides for 15 weeks increased steadily for the first few weeks and then reached a plateau or increased only slightly until pesticide feeding was terminated. By the end of the 5th week of pesticide feeding all pesticides except DDT had exceeded FDA action levels for pesticides in eggs. DDT residues reached a level of 0.139 p.p.m. by 8 weeks and did not increase thereafter. Traces of the pesticides were still present 24 weeks after termination of pesticide feeding. The pesticides tested did not affect fertility of hatchability of eggs collected during the 14th and 15th weeks of pesticide feeding. Total carcass fat of chicks hatched from these eggs had 0.024 p.p.m. dieldrin, .049 p.p.m. DDT, .001 p.p.m. heptachlor epoxide and, 0.47 mirex at 1 day of age.

No products of DDT metabolism were detected in surface seawater at temperatures of 4° to 32°C, at various salinities and in the presence or absence of O2. DDD was formed from DDT in surface waters supplemented with Cylindrospermum sp. cells, and both DDD and DDE were produced in surface water-sediment model ecosystems receiving organic amendments. Flooded sediments were especially active in converting DDT to DDD, and an unknown compound accumulated in these sediments. None of a series of compounds known to be generated microbiologically from DDT in vitro was observed in the model ecosystems.

(1982). The Effect of Nonabsorbable Lipids on the Intestinal Absorption of Lipophiles. Drug Metabolism Reviews: Vol. 13, No. 4, pp. 695-714.

Starlings fed 4.75 mg radioactive DDT per day for 5 days absorbed less than 25% of the insecticide. Concentrations remained high in the body and liver for 1 week after the feeding period, but decreased more quickly in the brain. After 10 days, less than 10% of the ingested DDT remained in the birds.

The amounts of organochlorine insecticides in the diet of the general population of Great Britain has been estimated by analyzing representative whole cooked meals. The methods of quantitation are briefly outlined and techniques suitable for qualitative confirmation of identity of these compounds are discussed. The estimated dietary intakes are compared with the food in other dietary surveys and, in the case of dieldrin, they are also compared with the amounts calculated from the concentrations of this compound in body fat and blood. The dietary intakes of dieldrin in 1965–1966 and 1967 were estimated to be 0.00030 and 0.00020 mg/kg/day, respectively, the difference being statistically significant. The maximum estimated intakes of total equivalent DDT were 0.0011 and 0.0014, respectively.

1. 1. Microsomes prepared from Triatoma infestans fifth-instar larvae metabolize DDT to a compound similar to Kelthane (metabolite No. 3), and to a derivative of apparently a phenolic nature (metabolite No. 2). 2. 2. The production of both metabolites requires either NADPH or NADH, but only the formation of metabolite No. 3 is nicotinamide—and magnesium— dependent. 3. 3. Optimum pH for the formation of metabolite No. 3 is 8·5, while it is 9·0 for metabolite No. 2. The K m values for each activity were also slightly different. 4. 4. The activity for each metabolite was increased by pretreatment with phenobarbital, but the induction kinetics was different in each case. 5. 5. These observations suggest that two rather than one microsomal enzyme are involved in DDT metabolism in T. infestans .

1. After administration of p, p'-DDT to pregnant rabbits DDT and its metabolites are found in high concn. in both the foetus and the organs of the maternal rabbit which regulate the foetal environment.2. p.p''-DDT does not rapidly leave the foetal tissue, as whole body levels at day 26 (17 days after DDT dosing) are higher than those in foetal plasma; foetal whole body levels are also higher than those found in placenta or maternal plasma, and half of those of maternal liver.3. p.p'-DDT treatment of pregnant rabbits at doses of 10 and 50 mg/kg caused an increased incidence of prematurity, an increase in the number of foetal resorptions and a decrease in foetal weight.4. These doses of DDT did not increase the incidence of chromosomal aberrations in the maternal or foetal tissue and exposure in vitro to levels as high as 100 μg/ml caused no abnormalities.

T. Randall Wrenn, Joan R. Weyant, George F. Fries and Joel BitmanEwesInfluence of Dietary o,p¢-DDT on Reproduction and Lactation ofJ ANIM SCI€1971, 33:1288-1292.http://jas.fass.org/content/33/6/1288services, is located on the World Wide Web at: The online version of this article, along with updated information and

Adults of the lady beetle Coleomegilla maculata De Geer, were topically treated with 40 μg of DDT. DDT and DDE were extracted with acetonitrile, partitioned with n-hexane, and determined by gas-liquid chromatography using an electron capture detector. DDT was metabolized to DDE. DDE [1,1-dichloro-2,2-bis ( P -chlorophenyl) ethylene] probably was the only metabolite of DDT, since most of the applied dose was accounted for as DDT and DDE. In addition to metabolizing DDT to DDE, these beetles resist DDT poisoning by excreting DDT and DDE in the feces and eggs as much as 5 μg of DDT-DDE were present in an average egg mass and as much as 1.1 μg of DDTDDE were excreted in the feces per day. For 3-4 days after DDT treatment, feces contained greater amount of DDT than DDE; after 5 days the quantity of DDE exceeded that of DDT in both feces and eggs. When lady beetles were topically treated with 40 μg of DDT, the dead insects contained about 1.5 to 2 times as much DDT as the surviving individuals. A large part of this difference was probably caused by the metabolism of DDT to DDE, since during the first 5 days after treatment with DDT, the surviving beetles contained more DDE than the dead individuals. Resistance of C. maeulata to DDT is due at least in part to its ability to metabolize DDT to DDE and to excrete these 2 compounds in feces and eggs.

It has been demonstrated by Sternburg et al , (1950) and Perry and Hoskins (1950) that certain strains of DDT-resistant house flies have an abnormal facility to degrade DDT to its non-toxic metabolite DDE (1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene). The difference between susceptible and resistant strains is so great in this respect that it would seem to be a major factor in the explanation of the nature of DDT-resistance. It seemed that further studies on the metabolism of DDT by the two strains of flies might lead to a clarification of the significance of DDT-degradation in relation to the acquisition of DDT-resistance and at the same time contribute much needed information on the mode of action of DDT. The previous work indicated the need for information concerning the site or sites at which DDT is degraded in resistant flies. It also seemed desirable to extend the studies on DDT metabolism to stages other than the adult.

(1972). Interactions of Halogenated Pesticides and Microorganisms: A Review. CRC Critical Reviews in Microbiology: Vol. 2, No. 1, pp. 1-33.

1. (1) Nymph and male T. infestans specimens differ in their rate of absorption, excretion and metabolism of C14-DDT. Nymphs absorb DDT to a lesser extent than males. Furthermore, DDT is excreted at a faster rate in nymphs than males. After 96 hours of intoxication, 27.5% of the absorbed DDT is converted to a mixture of five metabolites in nymphs, while only 4.7% of the absorbed DDT is accounted for by DDT-metabolites in males after the same time of intoxication. 2. (2) DDT is metabolized into five metabolites in both nymph and male adult T. infestans. DDE is the major DDT-metabolite produced by nymphs, while in males, metabolite No. 5 is the most important one, DDE being found only in negligible amounts. Metabolite 3 has the same Chromatographic identity as Kelthane, a DDT metabolite found in Drosophila and Blattella germanica. 3. (3) It is postulated that the production of the more polar metabolites involves oxidative processes independent of the mechanism of formation of DDE. A tentative sequence is given for the formation of DDT metabolites in T. infestans and the availability of TPNH is suggested as a common link for both the oxidation and the dehydrochlorination processes. 4. (4) It is considered that the differences regarding DDT penetration, excretion, and metabolism shown by nymphs as compared to males, may account at least partly for the higher tolerance to DDT exhibited by nymph T. infestans.

Human subjects ingested daily 5- to 20-mg doses of technical DDT, p,p′-DDE, or p,p′-DDD for 81 to 183 days. Serum and adipose concentrations of DDT and DDT metabolites in response to these dosings have indicated that the initial dechlorination of DDT is of critical importance to its metabolic fate. Conversion to the saturated p,p′-DDD makes possible further degradation to the readily excreted p,p′-DDA. Dehydrochlorination, on the other hand, yields p,p′-DDE, a stable metabolite that is avidly retained in adipose storage. In two subjects ingesting technical DDT, conversion to DDE has been extremely limited, while conversion to DDD has been regularly demonstrable during and after dosing. Tissue stores of p,p′-DDE in general population probably originate mainly from preformed dietary p,p′-DDE in the diet, rather than from p,p′-DDT.

A Pseudomonas sp. rapidly metabolized several nonchlorinated analogues of DDT, with the exception of 2,2-diphenylethanol, as the sole carbon source. Several of the mono-p-chloro-substituted diphenyl analogues were also metabolized as the sole carbon source by the bacterium. The resulting chlorinated aromatic acid metabolites were not further metabolized. The isolate was unable to metabolize p,p'-dichlorodiphenyl analogues as the sole carbon source.

The metabolic fate of DDT1 is of interest not only because of widespread concern for environmental pollution but also because it affords an opportunity to study the complex metabolic reactions carried out in different organisms and various other ecosystems. Although DDT has been used for more than three decades, much of the knowledge of its metabolism in different systems is incomplete, misleading, or fraught with inconsistencies. Only with the advent of gas-liquid (GLC) and thin-layer chromatography (TLC) and mass spectrometry (MS) coupled with more extensive use of radiolabeled compounds has real progress been made.

1. DDT metabolism in a North American species of planarian leads to the formation of metabolites more toxic than the parent compound. 2. The increased toxicity of DDT metabolites is similar to acute toxicity data reported previously in a European species. 3. It is suggested that planarians lack a direct mechanism for DDT detoxification, since two North American and one European species are known to metabolize DDT initially to DDE and DDD.

For a proper assessment of actual risks, it is essential that the interactions between different modes of administration of a toxicant be understood and that the probable impingement of the environmental substances upon the various portals of entry be known. To best understand this last requirement we must know how the toxicants in question are distributed in and are transported through the environment to finally impact on man. In this review, we have attempted to evaluate but a small number of mutagens and potential mutagens ( e.g. , DDT and its metabolites, polychlorinated biphenyls, chlorinated dioxins, polycyclic aromatic hydrocarbons and haloethers) in terms of their occurrence, use patterns, distributions and impact in the environment. In many cases, the information is fragmentary. For example, patterns of region and local variation of the toxicants have been only superficially investigated and the detailed pathways of residues within the trophic networks are poorly understood. The physiological and ecological effects of the toxicants at sub-lethal levels are also to a large extent unknown. We must have more information as to (1) the production (nature of reactants, amounts, reactivity, disposal, etc.), import and export data for specific potential environmental toxicants, (2) the nature and routes of their global transport, and (3) the concentration, longevity, biochemical and toxicological activity of their residues (including specific chemical nature) that occur in their various biosphere compartments including air, water, soil, and biota.

An investigation was undertaken on the accumulation of DDT and its metabolites in the rat. Rats received 14.5 mg DDT/kg b.w. every day for 52 days. Growth, food intake, body composition, and the activities of various enzymes were little affected. However, the level of total lipids fell 30% and the weight of the liver rose 20% due to cellular hypertrophy induced by the DDT. The quantity of DDT and its metabolites found in the carcass was 24 mg/rat i.e. three times that found in rats dead after a single dose of 200 mg/kg. Liver and brain contained 130 micrograms/rat and 10 micrograms/rat, respectively i.e. five times lower than those found in the rats which died from an acute dose of DDT. In the carcass, p,p' DDT accumulates more than p,p' DDE or p,p' DDD; the latter is preponderant in the liver.

Publisher Summary This chapter discusses the pharmacological basis of DDT and related chlorinated hydrocarbon insecticides toxicity in mammals. In mammals, the administration of acute large doses of DDT and related chlorinated hydrocarbon insecticides produces a variety of toxic effects and invariably leads to death. Methoxychlor, that appears to be replacing DDT in certain countries, exhibits toxicity that is about 30 times less than that seen with DDT. The major routes of DDT metabolism in mammals are (1) oxidation to DDA, (2) dehydrochlorination to DDE, and (3) reductive dechlorination to DDD. In vertebrates, the major metabolite of DDT in feces and urine is DDA. Of DDT-derived, ether-soluble material in the rat bile, DDT constitutes about 3%, DDE 1%, and free DDA 25-35%; the remaining consists of complexes of DDA or a closely related material. DDE is the principal storage form of ingested DDT in man. However, while men stores about 60% of DDT-derived material in the form of DDE, rats store only about 22-29% of DDE, and monkeys convert little or no DDT to DDE.

Dietary polychlorinated biphenyls (PCBs), DDT and related compounds, in well controlled experiments, produced no detrimental effects upon egg shell quality in Single Comb White Leghorm chickens or in Japanese quail. PCBs caused some decrease in egg production and a drastic reduction in hatchability in chickens, but not in Japanese quail. Inorganic mercury as HgSO4 or HgCl2, at dietary levels up to 200 p.p.m. of Hg, had only small effects, if any, upon egg production, hatchability, shell quality, morbidity and mortality. However, methyl mercury chloride at levels which provided 10 or 20 mg. of Hg per kg. of diet caused severe effects upon egg weight, egg production, fertility, hatchability, egg shell strength, morbidity and mortality. The results of these experiments demonstrate that the decrease in egg shell quality which has occurred in eggs of White Leghorn hens over the past three decades is not due to contamination of commercial feeds with DDT or its derivatives, or with PCBs. The extent to which environmental contamination with methyl mercury is responsible for decreased egg shell strength in commercial laying hens, and possible synergistic relationships between methyl mercury, DDT, DDE and PCBs in reducing egg production, hatchability and shell strength, remain to be determined.

Technical grade DDT was fed to Pennsylvania white-tail deer in five experiments lasting 100 days at several dose levels to determine the chronic and acute effects on the deer as well as the nature and distribution of DDT metabolites in selected tissues and organs, feces, and urine. The dosage of three experiments was constant at levels of 10-10 4 μg/g DDT in the feed. The dosage of the two remaining experiments was attenuated, beginning at levels of 50, 175, or 350 μg/g and ending at 1 μg/g. Total DDT concentrations found in feces and urine were an order of magnitude below feeding concentrations. Highest concentrations found from constant diets were in bone marrow, fat, and liver tissues; lower amounts in kidney, brain, and muscle; and lowest amounts in blood. For attenuated diets, concentrations found in these tissues were negligible. TDE was the major metabolite found in tissues and organs, ranging from 91-31% ( =56%) of the total DDT type residues in liver, kidney, fat, blood, muscle, brain, and bone marrow. TDE in feces was 65% of the total residue. DDA was the major metabolite in urine, comprising 87% of the total residue .

Oral doses of DDT (5, 10, 20 mg/day) DDE, DDD, and DDA (5 mg/day) administered to human volunteers are, in part, excreted as DDA in the following order: DDA>DDD>DDT. Ingestion of DDE failed to produce any increase of DDA excretion. Increased urinary DDA excretion is detectible within 24 hours of DDT, DDD, or DDA ingestion. DDA excretion returns to predose levels within two to three days of dose termination for DDA but continues significantly above predose levels for over four months following termination of DDD or DDT doses.

Before and immediately after a 10-day period of partial starvation and again after 40 additional days' recovery, DDT and its metabolites were measured in the fat of rats fed traces of the insecticide and in the fat, plasma, brain, liver, kidney, urine, and feces of rats fed the compound at a rate of 200 ppm. Mobilization of body fat during starvation resulted in an increased concentration of DDT-derived material in that tissue and a corresponding increase in the other tissues. An augmented excretion of metabolites occurred during starvation in spite of decreased intake of DDT. The increased excretion was inadequate to prevent the increase in concentration of DDT-derived material in the body although it tended to do so. When sufficiently great, the augmented concentration of DDT in the brain associated with starvation was correlated with the occurrence of signs of poisoning. Storage and excretion tended to return to prestarvation levels during recovery, but some lack of parallelism was observed between the concentration of DDT-derived materials in brain, liver, and kidney as compared with fat and plasma.

The influence of diethylstilbestrol (DES) and testosterone propionate (TP) on the storage of DDT and its metabolite, DDE, was studied in normal and in gonadectomized rats. As expected, TP dosage increased the growth of female rats while DES administration inhibited the growth of males. Both hormones inhibited gonadal growth. Rats that received either DDT or hormone showed an increased liver weight/body weight ratio as compared to control animals. This effect was more marked in males than in females. DES increased DDT and DDE storage in fat in the male while TP decreased these values in the female. Similar effects of hormone dosage were noted on the ratio of DDE to total DDT-derived material stored in fat.

THE main cause of resistance to DDT in insects is an increased rate of detoxication, although other mechanisms (such as higher lipid content, or lower nerve sheath permeability) have been suggested1. Products of DDT-metabolism in insects are DDE, kelthan, and water soluble conjugates1, while yeast2 and rat liver3 metabolize DDT to TDE.