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Since 1987, the World Health Organization (WHO) carried out global surveys on polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in human milk. This study presents a review of the three most recent surveys from 2000 to 2010, including DDT. The objective was to identify global quantitative differences and provide baseline information for 52 countries or provide time-trends for countries with previous data. Individual human milk samples were collected following a WHO-designed procedure and combined to form a national pooled sample. Here, we report global levels for PCDDs, PCDFs, PCBs and the sum of o,p'-DDT, p,p'-DDT, o,p'-DDE, p,p'-DDE, o,p'-DDD and p,p'-DDD (ΣDDTs). A concise risk-benefit evaluation related to human milk contamination with these persistent organic pollutants (POPs) was also done. Large global and regional differences were observed. Levels of PCDDs and PCDFs were highest in India and some European and African countries. PCB levels were highest in East and West Europe. The highest levels of ΣDDTs were found in less industrialized countries. A temporal downward trend for PCDDs, PCDFs and PCBs is indicated. A risk-benefit assessment indicates that human milk levels of PCDDs, PCDFs and PCBs are still significantly above those considered toxicologically safe, while ΣDDTs are below or around those considered safe. With respect to potential adverse health effects, a more dominant role of in utero exposure versus lactational exposure is indicated. If potential adverse effects are balanced against positive health aspects for (breastfed) infants, the advantages of breastfeeding far outweigh the possible disadvantages. Our observations provide a strong argument to plea for further global source-directed measures to reduce human exposure further to dioxin-like compounds.

Ionic liquids are a kind of environmentally friendly solvents which have drawn great attention in many fields. The potential of ionic liquid as dispersive liquidphase microextraction (DLPME) solvent for the enrichment of typical persistent organic pollutants, dichlorodiphenyltrichloroethane (DDT), and its metabolites including 1,1-dichloro-2,2-bis-(4'-chlorophenyl)ethane and 1,1-dichloro-2,2-bis-(4'-chlorophenyl)ethylene has been investigated. Parameters that may influence the extraction efficiency, such as the type and volume of ionic liquid, the type and volume of disperser solvent, extraction time, and sample pH, were investigated and optimized in detail. The experimental results showed the excellent linear relationship between peak area and the concentration of DDT and its metabolites over the range of 1-50 μg L⁻¹, and the precisions (RSDs) were 5.27-6.73% under the optimal conditions. The limits of detection could reach 0.33-0.63 μg L⁻¹. Satisfied results were achieved when the proposed method was applied to determine the target compounds in real-world water samples with spiked recoveries over the range 94.4-115.3%. All these facts indicated that ionic liquid DLPME coupled to HPLC was an environmentally friendly alternative for the rapid analysis of DDT and its metabolites at trace level in environmental water samples.

To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p'-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT-PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells. We tested auraptene on DDT-induced reactive oxygen species (ROS) formation in U937 macrophages and found that auraptene is a powerful agent antagonizing this action of DDT. To confirm the significance of these actions of zerumbone and auraptene at the cellular level, we assessed their influence on TCDD-induced apoptosis resistance in intact U937 macrophages and found that they are capable of reversing this action of TCDD. In conclusion, zerumbone and auraptene were identified to be the most effective agents in protecting U937 macrophages from developing these cell toxic effects of TCDD and DDT.

Fish and mollusk samples were collected from markets located in 12 cities in Liaoning province, China, during August and September 2007, and 22 organochlorine pesticides (OCPs) were detected. DDT, HCH, endosulfan, chlordane, and HCB were the dominating OCPs, with mean concentrations and ranges of, respectively, 15.41 and 0.57 to 177.56 ng/g, 0.84 and below detection limit (BDL) to 22.99 ng/g, 1.31 and BDL to 13.1 ng/g, 1.05 and BDL to 15.68 ng/g, and 0.63 and BDL to 9.21 ng/g in all fish and mollusk samples. The concentrations of other OCPs generally were low and were detectable in a minority of samples, reflecting the low levels of these OCPs in the study region. In general, OCP concentrations were obviously higher in fish than in mollusks, and higher in freshwater fish than in marine fish, which indicated, first, that freshwater fish are more easily influenced than seawater fish and mollusks by OCP residues in agricultural areas and, second, that there are different biota accumulation factors for OCPs between fish and mollusk. To learn the consumption of fish and mollusk, 256 questionnaires were sent to families in 12 cities of Liaoning province. Using the contamination data, average estimated daily intakes of OCPs via fish and mollusk consumption were calculated, which were used for exposure assessment. The public health risks caused by exposure to OCPs in the course of fish and mollusk consumption were compared to noncancer benchmarks and cancer benchmarks.

Six species of freshwater fish collected from 10 fishponds in Shunde and Zhongshan, China, four species of marine fishes collected from different mariculture farms [four in Hong Kong (Tung Lung Chau, Ma Wan, Cheung Chau and Kat O) and two in mainland China (Daya Bay and Shenzhen)] together with feed (both trash fish and commercial pellets) and sediment were analyzed for DDTs. Total DDTs in freshwater fish flesh decreased in the order of: carnivores [1742 microg/kg lipid weight (l.w.)] > herbivores (165 microg/kg, l.w.) > omnivores (42.5 microg/kg, l.w.), with the highest concentration detected in mandarin fish (Siniperca chuatsi) (2641 microg/kg, l.w.). For marine fish, snubnose pompano (Trachinotus blochii) and orange-spotted grouper (Epinephelus coioides) collected in Ma Wan contained elevated levels of total DDTs (2590 and 2034 microg/kg l.w., respectively). Trash fish used in both freshwater and marine fish farms contained significantly higher levels (86.5-641 microg/kg l.w.) (p < 0.05) of DDTs than in commercial pellets, but correlations between DDT levels in fish feed and muscle were not significant. The elevated biota-sediment accumulating factor for tilapia (Tilapia mossambicus) (24.1) indicated that accumulation of DDTs from sediment to the fish was evident. It can be concluded that trash fish should not be used for fish culture in order to lower the level of residual DDTs in fish muscle.

Peregrine falcons were extirpated from the eastern United States by 1964 due to the effects of dichloro-diphenyl-trichlorethane (DDT) (Peakall and Kiff 1988). As a result of restoration efforts, peregrines have largely recovered in the region but remain a barometer of environmental contamination. In the course of monitoring nests, biologists in the mid-Atlantic states collected peregrine falcon eggs that failed to hatch. In the period 1993-1999, 93 eggs were collected from 66 nests in 31 locations in New Jersey, Pennsylvania, Delaware, Maryland, and Virginia. We analyzed eggs for organochlorine pesticides, PCBs, and metals, and calculated toxic equivalencies (TEQs) for dioxins and furans. Organochlorine contaminants were detected in eggs from all parts of the region. Although nest success in all parts of the region was good, the PCB TEQ in the Atlantic-New Jersey region was significantly related to nest success, and the regionwide PCB TEQ was nearly significant for nest success across the five-state area. dichloro-diphenyl-dichloroethylene (DDE), DDT, and total PCBs were negatively correlated with eggshell thickness, although eggshell thinning (10.4%) was not at a level associated with deleterious population effects. The five states represented in this study are productive for peregrine falcons and have contributed to the recovery of this species. However, the results suggest that Atlantic coastal peregrines might be subject to contaminant burdens that have the potential to decrease nest success and productivity.

Seasonal trends and tissue distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in gilthead sea bream (Sparus aurata) samples from the Western Mediterranean were investigated. Hexane extracts of white and red muscle, liver, and gills from wild and cultured specimens were purified by normal-phase high-performance liquid chromatography, and selected OCPs and PCBs were determined by gas chromatography coupled to mass spectrometry as indicators of contamination. The limits of detection for the analytical methodology allowed was 0.25 ng/g. Data obtained showed the presence of DDTs and PCBs in the different tissues, with the highest concentration of pollutants being in tissues of higher lipid content. Concentrations of organochlorine compounds in sea bream tissues strongly correlated with seasonal changes and the biological cycle of the species. In general, cultured fish had lower concentrations of contaminants and smaller season variability than wild fish. Trace levels of contaminants were found in fish muscle throughout the year, but always below the guidelines recommended for human consumption.

Submarine canyons are regarded as a sink for pollutants. In order to determine if this theory applied to deep-sea species from an important fishing ground (the Blanes submarine canyon) located in the NW Mediterranean, we sampled the commercial fish Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus. Specimens were sampled inside and outside (in the open continental slope) the submarine canyon; both are regarded as potentially affected by exposure to different anthropogenic chemicals. Several pollution biomarkers in muscle (activity of cholinesterases) and liver/hepatopancreas (catalase, glutathione S-transferases, carboxylesterases, ethoxyresorufin O-deethylase in fish or mixed function oxygenase (MFO)-related reductases in crustacean, and lipid peroxidation levels) were measured. Chemical analysis of the persistent organic pollutants, namely polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) was also performed on the fish and crustacean muscle. Biomarker activities and levels were discussed in relation to pollutant exposure, habitat, and parameters including sex, size, and species. Biochemical responses and chemical analysis of PCBs evidenced interspecies differences as well as sex and size-related ones, mainly in A. antennatus. An indication of higher exposure to pollutants inside the canyon was observed, which was more clearly reflected in the fish than in the crustacean. However, further research is required to confirm this observation.

Persistent organochlorine pesticides (OCPs), such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) isomers, together with polychlorinated biphenyl (PCB) congeners (IUPAC Nos. 28, 52, 101, 138, 153, and 180) were determined in tail feathers from 35 birds belonging to 15 species, all originating from the southwest of Iran (Khuzestan, coast of the Persian Gulf) and kept in museum collections. The patterns of organochlorine contaminants (OCs) in birds varied depending on their migratory behavior. Resident birds contained higher median PCB concentrations (

Sacramento splittail (Pogonichthys macrolepidotus) is a species of special concern in California, due to multiple anthropogenic stressors. To better understand the potential impact of contaminant exposure, adult splittail were captured from the Sacramento-San Joaquin River Delta (California, USA) and analyzed for histopathology and contaminant exposure. Organochlorine contaminants (PCBs, DDTs, dieldrin, chlordanes, and PBDEs) and trace metals (Ag, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sn, V, and Zn) were detected in the tissues of all fish. In many samples, human health screening values were exceeded for PCBs (83 of 90 samples), DDTs (32 samples), and dieldrin (37 samples). In contrast, thresholds for fish effects were rarely exceeded. Histopathological analysis indicated the presence of macrophage aggregates in gonads, kidneys, and liver and a high incidence of liver abnormalities. In the liver, observed effects were often moderate to severe for glycogen depletion (55 of 95 fish), lipidosis (hepatocellular vacuolation; 51 fish), and cytoplasmic inclusion bodies (33 fish). Correlations between histopathology and tissue contaminant concentrations were weak and inconsistent. Significant correlations were observed between histopathology indicators and reductions in fish size, body condition, lipid content, and liver weight. These results suggest that splittail histopathology varies as a function of health and nutritional status, rather than exposure to legacy organic and metal pollutants.

Methoxychlor [1,1,1-trichloro-2,2-bis(p-methoxyphenyl)ethane], a substitute for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), is a compound of environmental concern because of potential long-term health risks related to its endocrine-disrupting and carcinogenic potency. In order to determine the metabolic fate of methoxychlor and DDT in the human intestinal gut, Eubacterium limosum (ATCC 8486), a strict anaerobe isolated from the human intestine that is capable of O-demethylation toward O-methylated isoflavones, was used as a model intestinal microbial organism. Under anaerobic incubation conditions, E. limosum completely transformed methoxychlor and DDT in 16 days. Based on gas chromatography-mass chromatography analyses, the metabolites produced from methoxychlor and DDT by E. limosum were confirmed to be 1,1-dichloro-2,2-bis(p-methoxyphenyl)ethane (methoxydichlor) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), respectively. This study suggests that E. limosum in the human intestinal gut might be a participant in the reductive dechlorination of methoxychlor to the more antiandrogenic active methoxydichlor.

Aim: To determine whether DDT uptake from chylomicrons (CM) into tissues is coincident with CM core lipid uptake., Method: CM were collected from mesenteric lymph duct cannulated, male Sprague-Dawley rats administered olive oil containing 3H-Cholesterol (converted to cholesterol ester (CE) during absorption through the intestine) and 14C-DDT by oral gavage. The CM were suspended in normal saline and 400 microL (containing 0.11 microCi/mL 14C-DDT and 0.15 microCi/mL 3H-CE) was administered via the jugular vein to the recipient rats. The blood was sampled periodically over 30 min from the carotid artery and at the end of the experiment the adrenal glands, brain, fat, heart, liver and spleen were collected. The concentration of 14C-DDT and 3H-CE in whole blood samples and tissue samples was then determined., Results: DDT was removed from the whole blood and, therefore, CM at a significantly faster rate than CE (alpha = 0.05). The tissue distribution of DDT was also different from that of CE, and DDT was particularly concentrated in the retriperitoneal fat and brain. For DDT, the values for VBdB and Cl were significantly higher compared with those determined for CE., Conclusion: DDT is absorbed predominantly via the intestinal lymphatic system in association with CM and accumulates in fatty tissues. This study furthers the understanding of the process of DDT uptake from CM into tissues and demonstrates that the uptake of DDT into tissues is faster than and independent of the uptake of CM core lipid (using CE as a marker). DDT was particularly concentrated in fatty tissues, accounting for its relatively high VBDB.

Organochlorine concentrations (OCs) and stable isotopes were investigated in the blubber of common dolphins (Delphinus delphis) and striped dolphins (Stenella coeruleoalba) from the southwestern Mediterranean. Samples were obtained from dolphins entangled in fishing nets during the 1992-1994 fishing season and from biopsies taken in 1992. Intrapopulation variations were studied, but because most of the dolphins were juveniles or calves (90%), no significant differences were found on the basis of reproductive condition or sex. Only mature male common dolphins showed significantly higher levels of most of the compounds studied than immature individuals did. There were quantitative and qualitative interspecific differences in organochlorine compounds profile. As compared to common dolphins, striped dolphins carried higher concentrations of organochlorine concentrations (OCs), their %DDE/tDDT and PCB/tDDT ratios were significantly higher, and recalcitrant PCB congeners were more abundant. Distribution and information on composition of stomach contents would in principle support a higher exposure to OCs in common dolphins as compared to striped dolphins, thus apparently contradicting the observed results. However, stable isotopes showed that striped dolphins exploit a higher trophic level, thus explaining observed differences. Interspecific dissimilarities in metabolic capacity to handle OCs may be an added factor. Although in the two species OC concentrations exceeded levels considered to be ineffective in marine mammals, pollution-induced effects on populations could not be properly assessed.

The exposure of red foxes to hexachlorobenzene (HCB), dichlorodiphenyltrichloroethan (DDT), DDT derivatives, and polychlorinated biphenyls (PCBs) in central Italy was determined by analyzing muscle and adipose tissue samples from 57 red foxes collected in 1992-1993 in three areas of Tuscany, each characterized by different levels of anthropization. Chemical analysis showed that HCB occurred in low concentrations, ranging from an average of 0.08 microg/g lipid basis in fat of foxes from Pisa, the least agricultural area, to 1.06 microg/g in muscle of those from Grosseto, the least industrialized area. DDTs were calculated as the sum of the op' and pp'DDT isomer concentrations and the DDT derivatives DDE and DDD. The lowest values of DDTs were found in foxes from Pisa, with mean values in muscle of 0.55 microg/g and 0.14 microg/g in fat. In the outskirts of Siena, the corresponding values were 1.16 microg/g and 0.49 microg/g. Higher values were found in the Grosseto area: 4.17 microg/g in muscle and 0.67 microg/g in fat. The most abundant DDT was pp'DDE in all areas, constituting more than half of total DDTs. Mean and standard deviations of PCB concentrations (calculated as the sum of the 31 identified and quantified congeners), were 20.2 microg/g in muscle and 7.2 microg/g in fat of red foxes from the Siena area. Values in the Pisa area were lower (7. 6 microg/g in muscle and 1.8 microg/g in fat), whereas the highest levels were found in the Grosseto area (38 microg/g in muscle and 7. 5 microg/g in fat). PCB fingerprints showed that hexa- and heptachlorobiphenyls were the most common congeners, although amounts differed between the three localities and the two tissues considered. As far as PCB composition is concerned, detailed observation revealed that although the three areas highly differed between each other, the most abundant congeners were the 22'344'5' (PCB 138) and 22'44'55' (PCB 153) hexachlorbiphenyls and 22'33'44'5 (PCB 170) and 22'344'55' (PCB 180) heptachlorobiphenyls; these accounted for over 60% of total PCB residues in muscle and fat. Concentrations of the remaining PCB congeners were all lower than 5% of total PCBs, with the exception of octachlorobiphenyl 22'33'44'55' (PCB 194) in fat tissue. Foxes may be suitable biological indicators to detect organochlorine contamination in the environment because of their catholic food habits. This information may be used to select specific bioindicators for assessing the relative level of pollutants in that area.

Wildlife contamination studies found high levels of DDT and associated metabolites in bird eggs from Canadian orchard sites during the early 1990s. The present study investigated local dietary uptake of DDT and geographic variability in tissue concentrations in the same orchards. A soil-earthworm-robin food chain was chosen for study, as early surveys showed that robins contained the highest levels of DDT of several avian species and because published research indicated that earthworms were a probable dietary exposure route. Organochlorine pesticides and PCBs were measured in soil, earthworm, robin egg, and robin nestling samples collected from fruit orchards and reference sites. High average DDE (soil: 5.2 mg/kg; earthworm: 52 mg/kg; robin egg: 484 mg/kg dry weight) and DDT (soil: 9.2 mg/kg; earthworm: 21 mg/kg; robin egg: 73 mg/kg dry weight) concentrations in Okanagan (British Columbia) samples confirmed that previously recorded contamination was common in the region. Concentrations detected in Simcoe, Ontario, orchards were not as high but were still significantly elevated relative to levels in soils and robins from reference areas. Significant positive linear regressions between soil and earthworm concentrations and consistent trends in food chain accumulation suggested that robins were acquiring DDT and metabolite (DDTr) burdens locally. Low concentrations of DDT and DDTr in robin eggs collected from nests in nearby nonorchard and post-DDT orchard habitats suggested that the local sources were in orchards. Persistence of DDT in orchard food chains is likely due to a combination of retarded degradation rates for DDT in soil and its extensive use historically. DDT concentrations in some robin eggs and earthworms were at levels comparable to those observed in field studies where mortality or reproductive effects occurred.

Twenty-eight tidal creeks along the South Carolina coast were sampled during the summer of 1995 to determine the levels of sediment contamination including organic chemicals (i.e., polycyclic aromatic hydrocarbons [PAHs], polychlorinated biphenyls [PCBs], and DDT and its metabolites) associated with different types and varying levels of watershed development (i.e., industrial/urban, suburban, forested, and salt marsh). Organic analysis utilized high-performance liquid chromatography (HPLC) with fluorescence detection and capillary gas chromatography-ion trap mass spectrometry (GC-ITMS) for PAHs, and gas chromatography with electron capture detection (GC-ECD) for pesticides and PCBs. Results indicated that creeks with industrial/urban watersheds had significantly higher concentrations of PAHs, PCBs, and DDT compared with creeks with suburban and forested (reference) watersheds. The suburban watershed class of creeks had concentrations of half the PAH analytes and the total PCBs which exceeded the concentrations found in the forested watershed class of creeks. The spatial distribution of organic contaminants was evaluated in four of these tidal creek-salt marsh systems representing urban/industrial, suburban, and forested watersheds, from the creek channel to the adjacent uplands. The distribution of organic contaminants within each representative creek was not concordant with the total organic carbon or the clay content of the sediment. The representative industrial/urban creek-marsh system, Diesel Creek, had the highest concentration of PAHs in the creek channel and the highest concentration of PCBs and DDT on the marsh surface, primarily in the upper portion of the system. The representative suburban creek-marsh system, Shem Creek, had elevated levels of both PAHs and PCBs throughout the entire system. This system also had one site with a total PAH concentration of 324,000 ppb and a total DDT concentration that was 20-100 times higher than the other sites. One of the representative forested creek-marsh systems, Rathall Creek, had low levels of the three organic contaminants except for one sampling site that had PAH concentrations a factor of 10 higher than the other sites. The other representative forested creek-marsh system, Long Creek, had low levels of PAHs and PCBs, but elevated levels of DDT were observed, particularly in the upper portion on the marsh surface. The results of this study suggest that (1) anthropogenic alteration of the land cover in the watersheds of tidal creek-salt marsh systems may increase the organic contaminant loadings in the sediment, and (2) tidal creek-salt marsh sediments, particularly in the creek channel, are repositories and potentially conduits of organic contaminants from the upland environment to the deeper estuarine areas.http://link.springer-ny. com/link/service/journals/00244/bibs/37n4p458.html

Previous studies demonstrated that Alcaligenes eutrophus A5 transforms 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) to 4-chlorobenzoate via a meta-ring fission product. The initial reactions could be catalyzed by either monooxygenase or dioxygenase enzymes. In the present study, a transient intermediate that accumulated during the transformation of DDT by the biphenyl-grown cells was identified as 1,1,1-trichloro-2-(4-chlorophenyl-2,3-dihydro-4,6-cyclohexadiene)-2-(4'- chlorophenyl)ethane (DDT-2,3-dihydrodiol) on the basis of mass spectral analysis after n-butylboronic acid derivatization. The dihydrodiol undergoes a characteristic acid-catalyzed dehydration to produce phenols. 1H-NMR indicated a cis-relative stereochemistry. The results indicate that the biphenyl dioxygenase from A. eutrophus A5 catalyzes the dihydroxylation of DDT at the unsubstituted carbons on the aromatic ring to produce DDT-2,3-dihydrodiol.

The body load of tDDT (p,p'DDT + o,p'DDT + p,p'DDE + p,p'TDE) and polychlorinated biphenyls (sum of congeners) was estimated for 169 fin whales to study age and sex-related variation and to calculate the quantity of these compounds transferred to offspring through reproduction. Blubber was the body compartment containing the greatest quantities of organochlorines, but its relative contribution to total load was lower than in other cetaceans because in fin whales muscle and bone are also significant lipid reserve sites. In male fin whales, organochlorine body loads increased with age but tended to reach a plateau in fully grown individuals. In adult females, loads decreased with age because of transfer to offspring cancelling the rise in loads associated with body growth; as a consequence, the amount of organochlorines transferred during a reproductive cycle also declined with age. This transfer is lower than that found for other cetaceans because fin whales have a shorter lactation period. According to the calculations, the first offspring of a female fin whale receives about 1 g of PCB and about 1.5 g of tDDT. These amounts will progressively decrease in subsequent reproductive cycles to reach a minimum of 0.2 g PCB and 0.3 g tDDT in an old female. Therefore, the first calf delivered is the one most likely to be affected by pollutants.

The biomagnification of polychlorinated biphenyls (PCB), toxaphene, and the DDT family of metabolites was investigated in the epibenthic Mysis relicta (mysid), the benthic Pontoporeia hoyi (amphipod), plankton, particulate flux, surficial sediments, and Myoxocephalus thompsoni (deepwater sculpin) in southeastern Lake Michigan. DDE was the most strongly biomagnified compound, increasing 28.7 times in average concentration from plankton to fish. PCB increased 12.9 times in average concentration from plankton to fish while toxaphene increased by an average factor of 4.7. Particle flux was comprised of lower chlorinated PCB homologues (average chlorine number = 3.8) than the biota (4.5-5.0) and sediments (4.6), possibly reflecting strong influences from atmospheric deposition and/or zooplankton egestion. The percent of higher chlorinated PCB homologues (5 and 6 chlorine atoms per PCB molecule) increased from 54-56% of the total PCB in plankton and M. relicta, to 61% in P. hoyi, to 74% in sculpins. Amphipods contained greater concentrations than mysids of PCB, DDT residues, and toxaphene, possibly reflecting differences in habitat (benthic vs epibenthic) and diet (detritus vs plankton). Based on estimates of average areal biomass and contaminant concentration, offshore Lake Michigan P. hoyi populations contain approximately 15.0 times as much toxaphene, 9.5 times as much total DDT, and 12.0 times as much PCB as the offshore M. relicta populations. Thus, amphipods may represent a greater reservoir than mysids for contaminant storage and subsequent recycling in offshore Lake Michigan.

Pregnant rats were given a small dose of 14C-2,4,5,2',4',5'-hexachlorobiphenyl (HCB) and 3H-DDT intraperitoneally. The transfer of HCB and DDT through the placenta and milk was then investigated. Transfer through the placenta was 2.7 and 1.5% (respectively) of the initial doses; transfer through milk was 39.2 and 21.5%. HCB is obviously more transferable than DDT through the placenta and milk, the ratio of the amount of HCB transferred through milk to the amount transferred through the placenta agrees with that for DDT. Concentrations of HCB and DDT in the whole suckling rat increases rapidly and is similar to the sigmoidal growth curve and change in lipid concentration. Therefore, the concentrations of the chemicals in the maternal tissue generally decrease in comparison with those of nonpregnant rats.

Blood serum of twenty workers occupationally exposed to DDT for an average duration of 14 years was analysed for organochlorine pesticides by gas-liquid chromatography with an electron capture detector. Significant levels of BHC, p,p'-DDT, p,p'-DDD and p,p'-DDE were detected. A higher incidence of total DDT equivalent, about 10 times, was observed in DDT exposed workers when compared with a comparable sample of unexposed persons from the general population. Levels of DDT in serum of occupationally exposed workers were more than the permitted level of 200 ppb. The daily intake was computed to be about 10 mg/man/day as against 0.25 mg--the acceptable daily intake. Abnormal nerve conduction was encountered in a few cases of DDT sprayers. No significant correlation was observed between the total DDT equivalent in serum and duration of occupational exposure in workers. Levels of BHC in controls was 2.3 times the level in exposed workers, possibly due to induction of hepatic drug metabolising enzymes by high levels of DDT in the latter group. Findings are discussed in the light of existing knowledge of the bio-chemical effects evoked due to residual intoxication of DDT during occupational exposure.

Serial observations of DDT-contaminated and uncontaminated salt marshes in the norther Gulf of Mexico were made in November and December, 1973. Blue crab (Callinectes sapidus) mortalities observed in the DDT-contaminated marsh during this period were correlated with reduced daily temperature minima. Gas chromatographic analysis of hepatopancreas and swimmeret muscle tissue of dead and dying crabs revealed total DDT residue concentrations as high as 39.0 ppm and 1.43 ppm, respectively. It is suggested that the DDT body burdens and reduced temperatures interact to produce acutely toxic effects. Several physiological and behavioral mechanisms are proposed.

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.

The effects of PCBs (polychlorinated biphenyls) or a combination of DDT (1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane), DDD (1,1-dichloro-2,2-bis (p-chlorophenyl) ethane) and DDE (1,1-dichloro-2,2,-bis (p-chlorophenyl ethylene) on organ weights, liver storage of vitamin A and carotene, selected blood chemistry parameters, and serum protein fractions were determined in penned white pelicans (Pelecanus erythrorhynchos) receiving a daily dosage of these compounds. Birds received 100 mg of PCBs or a combination of DDT (20 mg), DDD (15 mg), and DDE (15 mg) injected into the first fish fed each day for ten weeks. A greater percentage of PCB treatment was retained in brain, liver, carcass and feathers than the percentage of DDT + DDD + DDE treatment. Liver weight as percent of body weight decreased (p less than 0.01) in DDT + DDD + DDE-treated birds and increased (p less than 0.01) as a total weight in PCB-treated birds. Spleen weight as percent of body weight was greater (p less than 0.05) in PCB-treated birds. Neither treatment had a significant effect on the weight of the brain, heart, or kidney. Liver vitamin A levels were greater (p less than 0.01) on a mug/g of liver basis in the DDT-treated birds than in controls. Significant lowering of serum potassium and protein values was noted in both the PCB- and the combination of DDT, DDD, DDE-treated birds, while serum calcium values were lowered (p less than 0.01) only in PCB-treated birds. Vaues of serum inorganic phosphorus, uric acid and magnesium were not significantly changed by either treatment. Globulin fractions were unaltered by either treatment, but albumin fractions were lowered (p less than 0.01) in the PCB-treated pelicans.

Residues of dichlorodiphenyltrichloroethane (DDT) and its metabolites were monitored in leiomyomatous and normal human uterine tissue by gas-liquid chromatography (GLC). The metabolites detected were: 2,2-bis-(p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), 2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1,1-trichloroethane (o,p'-DDT), 2,2-bis-(p-chlorophenyl)-1,1-dichloroethane (p,p'-DDD) and 2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT). Total DDT ranged from 0.245 to 1.982 ppm, with a mean value of 0.845 ppm in leiomyomatous tissue. In normal human uterine tissue, total DDT ranged from 0.030 to 0.282 ppm, with a mean value of 0.103 ppm. Significantly higher levels of DDT and its metabolites in leiomyomatous tissue as compared to normal uterine tissue suggest their involvement in uterine leiomyomas. The data is discussed in the light of existing knowledge on estrogenic activity of DDT analogs and estrogen-influenced growth of uterine leiomyomas.

Loaches, Misgurnus anguillicaudatus (Cantor), a common fish in Taiwan, were treated with DDT, dieldrin, and monocrotophos by continuous exposure in aqueous solutions (or suspensions) and by injection. DDT and dieldrin were 150 and 220 times more toxic, respectively, than monocrotophos, to the fish exposed in aqueous solutions (24-hr LC50), but only 1/9 and 1/4 as toxic as monocrotophos by injection (24-hr LD50). Results of GLC analyses indicate that, at the end of 24-hr exposure, 96.5% of DDT, 92.7% of dieldrin, and 14.3% of monocrotophos were absorbed by loaches from aqueous solutions. The initial rates of absorption for DDT and dieldrin were about 10 to 20 times faster than that for monocrotophos. The large differences in relative toxicity may be due to partition distribution which in turn caused differences in absorption, as DDT and dieldrin are lipophilic and monocrotophos is hydrophilic. Statistical analysis of the relationship between fish toxicities and partition coefficients supports the present finding. The coefficient of correlation is 0.70 between parition coefficients (benzene/water) and toxicities to fish (rainbow trout) of 12 organophosphorus insecticides, 0.74 between coefficients and corrected fish toxicities, and 0.96 between partition coefficients and corrected fish toxicities for organophosphates only. Results of analyses are significant at less than 1% probability level. Similar correlation was also obtained between partition coefficients for hexane/water and toxicities of 8 organophosphorus and 5 organochlorine insecticides to rainbow trout.

Decreased DDT, DDD, DDE in blood and DDA in urine followed phenobarbital treatments (10 mg/kg/day, 11 days, intramuscular (im)) in three male rhesus monkeys (Macaca mulatta). Animals were fed DDT diets containing up to 500 ppm DDT during a 3-year period. Induction of liver monooxygenases was confirmed by reduced in vivo antipyrine plasma half-life and increased in vitro oxidation rates of dihydroisodrin, p-nitroanisole and benz(alpha)pyrene by homogenates of liver obtained from closed needle biopsy. Chlorohydrocarbon blood levels significantly decreased during the induction period (days 1-11). Concentrations on day 28 were at or below pre-DDT exposure levels. Urine DDA gradually decreased in all monkeys from days 16 to 28.

Seven-Generation Study (P-F6): The concentration and total retention of dieldrin or p,p'-DDT and metabolites were determined in the total carcass of Swiss-Webster mice fed dietary supplements of aldrin 5 or 10 ppm, or DDT 100 ppm, to age 260 days. All groups showed a significant increase in total body retention (and concentration) of dieldrin or total DDT in the total carcass of the F1, F2, and F3 generations. Generally, these increases were related directly to increases in total body lipids, when compared with the P generations. The control (pesticide-free) diet was fed to all F4 generation experimental mice from weaning to age 260. The pesticides absorbed by these animals while in utero and via lactation were found, at the time of sacrifice, to have been excreted completely. When the experimental diets were resumed with the weanlings of the F2 generations, a repetition of the general findings in the P and F1 generations was noted-demonstrating that pesticide retention and total body lipids are closely interrelated, and that a high body lipid content favors a high retention rate of these fat-soluble pesticides. These results support our earlier studies in rats (Deichmann et al., 1972) and investigations with cirrhotic human livers with severe fatty infiltration (Oloffs et al., 1974). Conception became more delayed with each succeeding generation, requiring some degree of "selective" breeding of the F4, F5, and F6 generations.

DDT was administered to the guinea pig, mouse and rat either ig or ip and to the hamster ig in order to investigate variations in the response of hepatic and duodenal drug-metabolizing enzymes to DDT. The intragastric dose (160 mg/kg) was found to produce gastric bleeding and severe tremor in rats and mice but not in other rodents. The hepatic aryl hydrocarbon hydroxylase activity and cytochrome P-450 concentration decreased after the ig administration of DDT to rats, mice and guinea pigs but in hamsters the activiy of aryl hydrocarbon hydroxylase and cytochrome P-450 concentration increased 12 hr after the dosage. The aryl hydrocarbon hydroxylase activity decreased also in the duodenal mucosa of the rat after the ig administration of DDT. The ip dose had no effects on the hepatic or duodenal monooxygenase system in 12 hr. The UDPglucuronosyltransferase activity was slightly lowered in hepatic microsomes of the rat and mouse after the ig dose of DDT, but the decrease was more profound when measured after in vitro trypsin digestion of microsomes. The trypsin digestion activated the hepatic UDPglucuronosyltransferase in all the species studied, i.e., guinea pig, hamster, mouse and rat (3-, 3-, 5-, and 8-fold, respectively). The duodenal UDPglucuronosyltransferase activity was not affected by DDT administration in any of the species studied. The results suggest that the acute toxic effects of DDT are species-dependent and the administration route is important in DDT toxicity. The hydroxylation step in drug metabolism is more sensitive to DDT than the glucuronidation step.

Activities of enzymes involved in the metabolic formation and catabolism of epoxides were determined in liver subcellular preparations from 11 mammalian species and various strains of mice. The most conspicuous finding was that the activities of the microsomal epoxide hydrolase were clearly lower in the mouse than in the other species. This invited the working hypothesis that epoxides may be involved in mouse liver carcinogenesis. The carcinogens may be metabolised themselves to reactive epoxides or they may modify the metabolism of epoxides formed from endogenous or other foreign compounds. To examine the former point, phenobarbital, DDT (1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane), lindane and benzo(a)pyrene were investigated for mutagenicity in Salmonella typhimurium using as the carcinogen-metabolising system subcellular liver preparations from animals in which these compounds efficiently induce liver tumours and from resistant animals. Phenobarbital, DDT and lindane were not mutagenic under any conditions, including those where microsomal epoxide hydrolase was also inhibited. However, a DDT metabolite, 1,1-bis(p-chlorophenyl)-2,2-dichloroethane was mutagenic in strain TA98, when norharman was added to the metabolising system, rat liver postmitochondrial fraction. Benzo(a)pyrene, which efficiently induces liver tumours in male but not in female newborn C3HeB/FeJ X A/J mice, was similarly activated by liver preparations from male and female animals. This was true with and without pretreatment of the mice with an inducer of cytochrome P-448. Also, activities and inducibilities of monooxygenase, epoxide hydrolase and glutathione transferase (toward benzo(a)pyrene and benzo(a)pyrene 4,5-oxide, respectively) were indistinguishable between males and females. Therefore, differences in the metabolism of benzo(a)pyrene do not appear to be the reason for the sex difference in tumour susceptibility. Likewise, mouse strains with high and low frequencies of spontaneous and chemically-induced liver tumours did not appreciably differ in their hepatic microsomal epoxide hydrolase activities. The low level of this activity therefore cannot constitute the critical factor for the high tumour susceptibility of certain strains of mice. However the statement does not preclude potentiation of the susceptibility toward particular carcinogens owing to this metabolic trait of the mouse.

The toxicity, absorption, distribution, metabolism, and effects on reproduction of DDT was studied using the killifish (Fundulus heteroclitus), a species of economic importance because of its widespread abundance and its presence toward the lower end of the food chain. 14C-DDT was administered by exposure from the ambient water. There was a rapid removal of the radioactive pesticide from the water accompanied by uptake of radioactivity primarily by carcass (primarily muscle tissue) and eggs of the fish. Most (greater than 92%) of the radioactivity in the carcass was shown by TLC methods to be the parent pesticide. One day after a single 24-hr exposure to 14C-DDT, approximately 70% of the administered radioactivity was found in the carcass and the levels of the tissue decayed with a t 1/2 of three days. One day after a single 24-hr exposure to 0.1 ppm of 14C-DDT, the organs that contained the highest concentration of the pesticide (ca. 5 ppm) were intestine and liver. When the pesticide was administered by two 24-hr exposures from water, the intestine, liver and ovaries contained the major concentration of radioactivity (7 to 14 ppm). Untreated Fundulus contained less than 0.2 ppm of total DDT-like compounds. A variety of doses and schedules were tested in an effort to maximize the absorption of DDT, while minimizing the mortality to the fish. An intermittent schedule of 24 hr in 0.1 ppm DDT followed by 24 hr in DDT-free sea water, repeated two times, was found to be optimal. At the levels examined, DDT delayed the rate of normal development of fertilized eggs from Fundulus, but did not appear to cause any observable alterations in the hatched fry. Fertilization of Fundulus eggs was significantly diminished when insemination was carried out in DDT-containing sea water.

The effects of greatly reduced food intake were investigated in rats which had accumulated three times as much DDT as rats killed with a single dose approaching LD50. DDT and its metabolites mobilized more quickly than the fat deposits. The hypertrophy of the liver due to DDT decreased during food restriction and demonstrated the existence of a large detoxication capacity shown through the high metabolism of the pesticide. The disappearance of p,p' DDE was most rapid, followed by p,p' DDD then p,p' DDT; they did not accumulate in the fat reserves. The half-life of the pesticide, which is normally three months in the rat, was reduced to five days under the experimental conditions. In spite of rapid mobilization, no major toxic signs were detected from either nutritional, physiopathological, or biochemical examinations.