Factors affecting levels of DDT and metabolites in human breast milk from Kwazulu

Concentrations of p,p'-DDT, p,p'-DDE, and p,p'-DDD have been determined in breast milk of mothers residing in two different areas of KwaZulu. Annual intradomiciliary application of DDT was used for the interruption of malaria transmission in one area, while the other served as the control. Milk from mothers living in DDT-treated dwellings had significantly higher mean levels of DDT and metabolites (mean sigma DDT 15.83 mg kg-1 in milk fat) than those from the control area (0.69 mg kg-1). The highest recorded sigma DDT value was 59.3 mg kg-1 (milk fat). Primiparous mothers from the malarious area had significantly more sigma DDT and metabolites (sigma DDT 24.82 mg kg-1) than multiparous mothers from the same area (mean 12.21 mg kg-1). Parity was the best predictor of DDT in breast milk of the exposed group. The percentage DDT and the sigma DDT increased significantly with an increase in parity. The same, but not significant, trend was also found for the control group. It was hypothesized that the increase in percentage DDT that occurred with higher parities was due to the uptake of DDT and elimination via milk. This process was faster than the uptake and endogenous formation of DDE. Designing predictive models using multiple regression was not very successful. The recorded levels do not represent an appreciable health risk to the mothers. From the literature it was deduced that at the recorded levels, a well-founded risk to the infants, particularly the firstborns, exists in sprayed areas.     

Organochlorine pesticide residues in chicken eggs: a survey

One hundred and five chicken egg samples were taken from seven geographical locations in Kenya and analyzed for organochlorine pesticide residues using gas-liquid chromatography. Nine organochlorine compounds were detected: alpha- and gamma-HCH/BHC (hexachlorocyclohexane/benzene hexachloride), aldrin, dieldrin, p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], p,p'-DDD (TDE) [2,2-bis(p-chlorophenyl)-1,1-dichloroethane] (tetrachlorodiphenylethane), o,p'-DDD [2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloroethane], o,p'-DDT [2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1,1-trichloroethane], and p,p'-DDT. Eighteen of the samples contained DDT levels exceeding the practical residue limit (0.5 ppm). The mean DDT residue content was 0.68 ppm, a result influenced greatly by the high contamination in the 18 samples. Both individual and mean residue levels for other organochlorine pesticides detected were well within the respective practical residue limits.     

Effect of single and repeated in vitro exposure of ovarian follicles to o,p'-DDT and p,p'-DDT and their metabolites

The aim of the presented study was to compare the effect of o,p'-DDT [1,1-dichloro-2,2-bis-(p,p'-chlorophenyl)-ethylene] and p,p'-DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)-ethane] and their metabolites DDE and DDD on estradiol secretion by ovarian follicles, the target organs of environmental estrogens. Theca interna (Tc) and granulosa cells (Gc) were collected from medium size porcine follicles and cultured as a monolayer. The cells were initially cultured for 24 h to allow attachment to the plates and then media were changed for the new ones and o,p'-DDT and p,p'-DDT and their metabolites: o,p'-DDE, p,p'-DDE and o,p'-DDD were added at doses of 4, 40, 400 ng and 4 microg/ml medium to investigate dose-dependent effects. Media were collected after 24 h and frozen for estradiol content determination. When the effect of single and repeated exposure was investigated, the lowest dose of 4 ng/ml and the highest one of 4 microg/ml were chosen on the basis of the results of Experiment 1. o,p'-DDT exerted antiestrogenic action at all doses used while its metabolites and p,p'-DDT and its metabolites decreased estradiol secretion only when present in the medium at a dose of 4 ng/ml. The highest doses caused the increase in estradiol secretion. Parent o,p'-DDT and its metabolites showed antiestrogenic action after single exposure to 4 ng/ml while parent p,p'-DDT and its metabolites caused estrogenic action. All investigated compounds, except o,p'-DDT, increased estradiol secretion after single exposure to the dose of 4 microg/ml. Repeated exposure resulted in a massive antiestrogenic action of all investigated chemicals. In conclusion, our study points to time-dependent effect of DDT and its metabolites on ovarian follicles with the strongest estrogenic properties observed after single exposure and antiestrogenic action caused by repeated exposure. Given the duration of folliculogenesis, one can imagine many different potential mechanisms by which DDT could influence steroidogenesis.     

DDT supports the growth of an estrogen-responsive tumor

MT2 cells, a clonal cell line of MTW9/PL cells originally obtained from a mammary adenocarcinoma, from estrogen-responsive tumors in Wistar-Furth rats. o,p'-DDT supports MT2 tumor growth at a rate similar to 17 beta-estradiol. This effect of o,p'-DDT is dose-dependent and specific, since the DDT congener p,p'-DDD, which does not bind to tumor estrogen receptors, does not support tumor growth. This is the first demonstration that DDT can support the growth of an estrogen-responsive tumor.     

Organochlorine compounds in adipose tissue of Greenlanders and southern Danes.

Abdominal fat tissue samples from the general population of Greenland and from southern Denmark were analyzed for o,p'-DDE and p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], p,p,-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], o,p'-DDT and p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], lindane (1,2,3,4,5,6-hexachlorocyclohexane), aldrin (1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-endo-exo-1,4:5,8-dimethanonaphthalene), dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-exo-1,4:5,8-dimethanonaphthalene), heptachlor (1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methanoindene), heptachlor epoxide, and polychlorinated biphenyls (PCBs). Fat tissue from Greenlanders contained significantly higher amounts of p,p'-DDE (p less than or equal to 0.05), p,p'-DDT (p less than or equal to 0.01), and total DDT (SIGMA DDT, the sum of DDT and its metabolites) (p less than or equal to 0.01) than southern Danes. Lindane, aldrin-like residue, dieldrin heptachlor-like residue, heptachlor epoxide, and PCBs were present in adipose tissue of both groups and there were no significant differences between the groups. The p,p'-DDE level in Greenland was lower than that in the United States, eastern Europe, and India. Among Greenlanders of different ages the highest sigma DDT was found in the age group of 22-45 yr; the content of PCBs increased with age. Among southern Danes the highest sigma DDT was found in a higher age group than in Greenlanders. Among Greenlanders the content of aldrin-like residue decreased with age and that of dieldrin increased with age. A significant correlation was found (on the basis of wet weight) between p,p'-DDE and PCB content in southern Danes (p less than or equal to 0.02). The correlation between sigma DDT and PCB content was also significant in this population (p less than or equal to 0.01). These two relationships were not significantly correlated for the Greenlanders. The DDE/PCB and sigma DDT/PCB ratios were higher in Greenlanders than in southern Danes. These ratios are age-dependent and are highest in the age group 22-45 yr among the Greenlanders. A low DDE/PCB ratio and a low sigma DDT/PCB ratio have been proposed as markers for industrialization. In Greenlanders p,p'-DDE represented about 70% of sigma DDT. For southern Danes this level was about 90%. The data obtained are presented and discussed on the basis of both lipid and wet weight levels.     

HCH and DDT residues in human placentas in Murcia (Spain)

Organochlorinated insecticides are ubiquitous toxicants that are transplacentally transferred from mother to fetus and are reported to produce adverse health effects in pregnant woman and neonates. To investigate hexachlorocyclohexane (HCH) and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) exposure in pregnant woman, a total of 102 placentas were analyzed by a gas chromatograph equipped with electron capture detector. Organochlorine residues were found in 69.6% of the samples. Lindane was detected in 24.5%, alpha-HCH in 2.9%, beta-HCH in 6.9%, p,p'-DDE in 44.1%, p,p'-DDT in 14.7% and p,p'-DDD in 10.8% of the samples. The pattern of dispersal by these substances in Murcia is similar to that described by different authors in other countries. Therefore, the past use of DDT and the present employment of lindane seem to be reflected in body tissues of the residents of this area.     

Malaria control and levels of DDT in serum of two populations in Kwazulu

Concentrations of p,p'-DDT, p,p'-DDE, and p,p'-DDD were determined in serum of members of households of two different areas of KwaZulu. Annual intradomiciliary application of DDT is used for the interruption of malaria transmission in one area (the exposed group) while the other served as the control. Demographic differences between the two groups resulted in significantly more females in the control group. The two groups were comparable with respect to age. Serum from household members living in DDT-treated dwellings had significantly higher (p less than .005) levels of sigma DDT and metabolites (mean sigma DDT 140.9 micrograms/l) than those from the control area (mean sigma DDT 6.04 micrograms/l). Percentage DDT was also significantly higher (p less than .05) in the exposed group (28.9%) than the control group (8.3%). sigma DDT for the 3-10 yr age interval (168.6 micrograms/l) was significantly higher (p less than .05) than the 20-29 (60.5 micrograms/l) and 30-39 (84.2 micrograms/l) yr age intervals. There seemed to be two groups with regard to accumulation and elimination. The age group 3-29 appeared to be eliminating DDT, most likely accumulated from contaminated breast milk, faster than they accumulated it. From around 29 yr of age accumulation predominated as the levels increased with age. Regression analysis suggested pharmacokinetic differences for DDE and DDT between the two groups. Liver function parameters between the two groups only differed significantly for gamma-glutamyl transferase (gamma GT) (p less than .005), but the influence of difference in alcohol consumption, which was significantly higher in the exposed group (p less than .0001), offered a better explanation. Those of the exposed group that consumed alcohol had a significantly higher (p less than .05) mean gamma GT level (41.5 IU/l) than those that did not (20.2 IU/l), but were not significantly different for sigma DDT (p greater than .05). The safety of DDT used in malaria control for subjects aged 3 and older was confirmed by the levels of DDT in serum when compared with other studies, which showed lack of any negative effects associated with these levels in adults, and an apparently normal liver function in the exposed and control groups.     

Investigation of the role of estrogenic action and prostaglandin E2 in DDT-stimulated rat uterine contractions ex vivo.

Previous work in our laboratory showed that o,p'-DDT increases the frequency of rat uterine contractions in vitro. The present study investigated whether this response was related to prostaglandin E2 (PGE2) release from the uterine strips or to the estrogenicity of o,p'-DDT. Contraction frequency was evaluated by recording isometric spontaneous contractions in longitudinal uterine strips from pregnant rats. Assessment of PGE2 levels in the muscle bath showed no significant differences between control and DDT-treated strips, although significant amounts of PGE2 were detected in both groups and increased contraction frequency was observed in o,p'-DDT-treated strips. Furthermore, a role for direct estrogenic action in the medication of o,p'-DDT-stimulated uterine contraction was not supported by the contractility data, because: (i) unlike o,p'-DDT, 17-beta-estradiol had no stimulatory effect, but instead exerted a significant inhibitory effect on uterine contraction; (ii) the estrogen antagonist, tamoxifen, failed to block the stimulatory effect of o,p'-DDT; and (iii) p,p'-DDD, a non-estrogenic DDT analogue, significantly stimulated contraction frequency, similar to o,p'-DDT. These results suggest that the stimulatory effect of o,p'-DDT on contraction frequency is not dependent on PGE2 release or direct estrogen receptor-related action.     

Reductive metabolism of p,p'-DDT and o,p'-DDT by rat liver cytochrome P450.

The in vitro metabolism of p,p'-DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], an important environmental pollutant, was examined in rat liver, focusing on reductive dechlorination. When p,p'-DDT was incubated with liver microsomes of rats in the presence of NADPH or NADH, a dechlorinated metabolite, p,p'-DDD [1,1-dichloro-2,2-bis(4-chlorophenyl)ethane], was formed under anaerobic conditions together with a dehydrochlorinated metabolite, p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene]. p,p'-DDE was also formed from p,p'-DDD by liver microsomes. The dechlorinating activity was inhibited by carbon monoxide, metyrapone, and SKF 525-A (proadifen hydrochloride), but the dehydrochlorinating activity was unaffected. The reductase activity toward p,p'-DDT was induced by the pretreatment of rats with phenobarbital and dexamethasone. The dechlorination was catalyzed enzymatically by recombinant cytochrome P450 2B1, 3A1, 2B6, and 3A4. When p,p'-DDT was incubated with liver microsomes of rats in the presence of both a reduced pyridine nucleotide and FMN, p,p'-DDD was also formed under anaerobic conditions. In this case, the dechlorinating activity was not abolished when the microsomes were boiled. The reductase activities were inhibited by carbon monoxide. Hematin exhibited reductase activity toward p,p'-DDT in the presence of NADH and FMN. The activity of hematin was also supported by FMNH(2). The reductive dechlorination also seems to proceed nonenzymatically with the reduced flavin, catalyzed by the heme group of cytochrome P450. Similar enzymatic and nonenzymatic reducing activities were observed toward o,p'-DDT [1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane].     

Studies on concentration of halogen derivatives in herbal products from various regions of Poland

The studies covered evaluation of levels of halogen derivative pesticides (p,p'-DDT and its metabolites p,p'-DDD and p,p'-DDE, as well as HCH, DMDT, aldrin and dieldrin) in herbal raw materials picked up in various regions of Poland in 1983. Qualitative analyses have been carried out with the TLC method whereas for quantitative analyses the GLC method has been applied. It has been found that the most frequently occurring are p,p'-DDT and its metabolites. The highest concentrations of these compounds have been observed in herbs from Lower Silesia and from the Bydgoszcz regions. Also in the region of Bia?ystok concentrations of these compounds are generally higher than in other parts of Poland. Other pesticides have been found in a lesser number of herbal raw materials and in considerably lower concentrations.     

Studies on contamination of vegetable drugs with halogen derivative pesticides. Part 1: Changes of concentrations of halogen derivatives in herbal raw materials within the period of 1980-1984

Levels of concentration of halogen derivatives (p,p'-DDT with metabolites p,p'-DDD and p,p'-DDE, HCH, DMDT, aldrin, dieldrin) and their changes in herbal raw materials commercially manufactured in Poland within the period of 1980-1984 have been analyzed (qualitative analyses by TLC, quantitation by GLC). Higher levels of these compounds in 1982 as compared with the periods of 1980-1981 and 1983-1984 has been noticed.     

Distribution of organochlorines and PCB congeners in Korean human tissues

In order to investigate the residual amounts of organochlorines and polychlorinated biphenyls (PCBs) in Korean human tissues (blood, adipose tissue, liver, kidney cortex, and lung), the samples were collected from the autopsied cadavers of 40 men and 40 women (from teens to seventies of age). Alpha-BHC, beta-BHC, gamma-BHC, delta-BHC, p,p'-DDT, p,p'-DDD, p,p'-DDE, endrin, dieldein, aldrin, and 7 marker PCBs (28, 52, 101, 118, 138, 153, and 180) were determined in human tissues. The levels of organochlorines and PCB congeners indicated that they have been widely distributed in Korean human body. Positive correlations in terms of age were observed for the following cases: p,p'-DDE, p,p'-DDT, Sigma-DDT, PCB 118, PCB 138, PCB 153, and Sigma-PCB in the adipose tissue, and p,p'-DDE in the lung. Concentration of these compounds showed a significant age-related increase. Accumulation of these compounds in aged people revealed that these compounds were more slowly eliminated in our environment and risk assessment was necessary for further proper action. Significant differences in the levels of PCBs between genders were found for PCB 118 in the adipose tissue and PCB 138 in the liver. Positive correlation coefficients between tissues were detected with p,p'-DDE and p-BHC.     

A further study on the reliability of toxicokinetic parameters for predicting hepatotoxicity in rats receiving a 28-day repeated administration of DDT

We previously demonstrated a good correlation between the increased relative liver weight caused by DDT and the area under the concentration-time curve (AUC) of DDT or the total DDT (T-DDT) in plasma and liver of rats in a 7-day repeated dose study at 1000 ppm. To confirm the reliability of AUC for predicting toxic responses at different dose levels, we conducted a further 28-day repeated dose study of p,p'-DDT in male F344 rats at dietary levels of 50, 160, and 500 ppm. Concentrations of DDT and its metabolites in plasma, brain, liver, and fat for each dose group were measured at various time intervals during the study. The concentrations of DDT and T-DDT in plasma and liver were compared with their AUCs in relation to hepatotoxic responses including increased relative liver weight, microsomal enzyme induction (CYP2B1), and inhibition of gap junctional intercellular communication. The coefficient (R(2)) values of each toxic response in correlation with AUCs were generally much higher than those with concentrations at any dose levels, although the R(2) values vary considerably among toxic parameters. These results have confirmed that the AUC of DDT or T-DDT in plasma or liver is a reliable marker for predicting hepatotoxicity caused by DDT in repeated dose studies.     

Organochlorine pesticides in human milk from different areas of Kenya 1983-1985

Residue levels of the chlorinated hydrocarbons p,p'-DDT (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane), p,p'-DDE (2,2-bis(p-chlorophenyl)-1,1-dichloroethane), hexachlorobenzene (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH), aldrin, dieldrin, and polychlorinated biphenyls (PCBs) were determined in human milk of Kenyan mothers living in different areas of Kenya. The main organochlorine contaminants found in all the milk samples analyzed were p,p'-DDT and p,p'-DDE. Great regional differences were found, and mean levels of sum DDT and DDT/DDE ratio ranged from 1.1 to 18.7 mg/kg milk fat and from 0.7 to 5.7, respectively. In general, relatively low residue levels of HCB, alpha-HCH, beta-HCH, aldrin, and dieldrin were detected in 59, 37, 27, 37, and 19%, respectively, of all the milk samples analyzed. Quantifiable residue levels of PCBs and alpha-HCH were not found. The results were examined in relation to differences in living conditions with regard to agricultural activities, dietary habits, and reported use of pesticides in the various sampling areas.     

Association of maternal blood pressure and hemoglobin level with organochlorines in human milk

Milk samples of women from the general population in Lucknow were analysed by gas-liquid chromatography to determine the concentration of organochlorine pesticides and their possible association with maternal characteristics. p,p'-DDT (dichloro diphenyltrichloroethane), p,p-DDE (dichloro diphenyltrichloroethylene), p,p'-DDD (dichloro diphenyl dichloroethane), alpha, beta gamma and delta isomers of hexachlorocyclohexane (HCH) and aldrin were detected. The calculated daily intake of DDT and HCH by the neonates exceeded their acceptable daily intake (ADI) set by the WHO. A statistically significant association was noted between alpha-HCH residues in milk and hemoglobin (Hb) level in maternal blood (P < 0.001). Also, there was a significant association between gamma-HCH and p,p'-DDT levels in milk and diastolic blood pressure of mother (P < 0.05). An apparent negative relationship between p,p'-DDE level in mother's milk and birthweight of the baby was also noticed (P < 0.05). These results highlight the need for periodic monitoring to determine organochlorine contamination in human milk and assess their impact on mother and on neonatal health.     

The presence of environmental pollutants in the semen of farm animals (bull,ram, goat,and boar)

Organochlorine pesticides and polychlorinated biphenyls are widely used in agriculture and industry, respectively, and may affect male reproduction function. Although several pollutants have been detected in human semen, similar studies in farm animals have not appeared. In the present study, the semen of bulls, rams, goats, and boars was assayed for the organochlorine pesticides hexachlorobenzene (HCB), hexachlorocyclohexane (HCH, alpha-, beta-, and gamma-isomers), dieldrin, and heptachlor epoxide, for DDT-related chemicals (o,p'-DDE, p,p'-DDE, p,p'-DDD, p,p'-DDT), and for the PCBs congeners (PCB-52, -101, -138, -150, and -180). In all species of farm animals, the most frequently detected pollutants were p,p'-DDE (80-100% of samples), HCB (73.9-100%), and gamma-HCH (69.6-100%). Species differences in the concentrations of HCB, alpha-, beta-, and gamma-HCH, dieldrin, p,p'-DDE, p,p'-DDD, and PCBs were noted as well as differences in the concentrations of some isomers of HCH, DDT-related chemicals, and PCB congeners in the same species.     

Distribution and metabolism of DDT in the catfish Heteropneustes fossilis in relation to the signs of poisoning

Adult male catfish, Heteropneustes fossilis (Bloch), were given a lethal dose of 800 mg DDT/kg as an im injection of 10% p,p′-DDT in peanut oil ($\text{w}\text{v}$) in the caudal region. The metabolites of DDT in various tissues were studied 24 hr after treatment. For DDT distribution studies, the treated animals were divided into 6 categories according to signs of poisoning: (1) no signs, (2) hyperexcitation, (3) tremors, (4) convulsions, (5) death, and (6) recovery. The concentration of DDT was determined in brain, spinal cord, liver, kidney and fat. Adequate replicates and controls were used in each case. p,p′-DDE was the only metabolite detected. The major proportion of DDE (10%), was found in the kidney, while liver and fat bodies contained slightly lesser amounts of DDE. The remainder was unchanged DDT. The concentration of DDT in the tissues increased with time and the severity of poisoning. The brain and spinal cord contained the lowest concentration of DDT, starting with 7.1 and 9.8 ppm when the fish showed no signs. The DDT content gradually rose to 50.5 and 58.7 ppm when the fish were dead, and declined to 9.1 and 19.0 ppm in fish which recovered completely. In fat, the DDT content continued to increase steadily and was maximal in fish which had recovered. The results indicate that signs of poisoning in the catfish were directly related to the concentration of DDT in the brain and spinal cord. The concentrations of DDT in brain and spinal cord of the catfish soon after death were similar to those found in some other vertebrates, e.g., rats, mice and a few species of birds, under identical circumstances.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin metabolism and disposition in yellow perch

Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were examined in fingerling yellow perch fed a diet containing 494 ppt of [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. None of the TCDD-exposed perch showed any signs of overt toxicity such as reduced growth rate, fin necrosis, cutaneous hemorrhage, or lethality. At the end of the 13-week exposure period, 78% of the total body burden of TCDD-derived 3H was contained in the carcass and visceral fat while the remaining 22% was distributed among the liver (9%), gill (5%), skin (3%), skeletal muscle (2%), gastrointestinal tract (1%), pyloric caeca (1%), kidney (less than 1%), spleen (less than 1%), and heart (less than 1%). High-performance liquid chromatographic analysis of organic extracts of visceral fat, carcass, liver, skeletal muscle, and skin showed that 96-99% of the tritium extracted from these tissues was due to the parent compound. The estimated t1/2 for whole-body depuration of TCDD-derived 3H was 18 weeks, and individual organ t1/2 values ranged from 6 to 19 weeks for the gastrointestinal tract, pyloric caeca, liver, gill, and carcass, and from 24 to 49 weeks for the visceral fat, kidney, skin, skeletal muscle, and spleen. To determine if yellow perch metabolize TCDD, a single dose of [14C]TCDD was administered to adult yellow perch (60 micrograms/kg, ip), and, 1 week later, gallbladder bile, liver, skeletal muscle, and kidney were removed, extracted, and analyzed by high-performance liquid chromatography. In contrast to the liver, muscle, and kidney where the parent compound accounted for 96-99% of the extractable 14C, the gallbladder bile contained almost entirely TCDD metabolites. At least four TCDD metabolites were detected in yellow perch bile and beta-glucuronidase treatment of the bile suggested that at least one was a glucuronide conjugate.     

A comparative study on the reliablility of toxicokinetic parameters for predicting hepatotoxicity of DDT in rats receiving a single or repeated administration

A comparative study on the reliability of toxicokinetic parameters for predicting hepatotoxicity was conducted in male F344 rats receiving a single (106 mg/kg by gavage) or 7-day repeated (1000 ppm in feed, 97 mg/kg/day) administration of p,p'-DDT. DDT was selected as the test substance because it is known as a hepatotoxic agent and its metabolic pathway is well documented. Concentrations of DDT and its metabolites (DDE and DDD) in the plasma, brain, and liver were measured at various time intervals during the study and the results were compared with the area under the concentration-time curve (AUC) in relation to hepatotoxic response. Increases in the absolute and relative (ratio to body weight) liver weights were observed as a typical toxic response after a single or repeated exposure to DDT. The coefficient (R2) of correlation between the increases in the relative liver weight and the concentrations or AUC of DDT and its metabolites in the plasma and liver was estimated. The values of R2 between the relative liver weight and AUC of DDT or the total DDT (T-DDT) in the plasma and liver were found to be more consistent and higher than those with their concentrations in the repeated dose study. In addition, the R2 values in correlation with their AUCs after a single exposure were lower than those in the repeated dose study. These results indicate that the AUC of DDT or T-DDT in the plasma and liver would be more reliable than their concentrations for predicting hepatotoxicity caused by DDT, especially in the repeated dose study.     

The lymphocytic absorption of p,p'-DDT and some structurally-related compounds in the rat.

The lymphatic absorption of a series of 14C-labelled compounds structurally related to p,p'-DDT has been examined in thoracic duct-cannulated rats. The compounds (p,p'-DDT, p,p-DDT, P,P'-DDD, p,p-DDD, DDE, DDA and 2,4-D) varied markedly in lipid solubility, as well as in extent of lymphatic absorption, urinary and biliary excretion, and localization in body fat. More than 12% of the dose was recovered in 24-hour thoracic duct lymph of rats treated with the p,p'- and o,p-isomers of DDT and DDD and with DDE, and this percentage was increased by concomitant fat absorption. A strict parallel between lipid solubility and lymphatic absorption was not observed in this series of compounds, possibly because of differences in their rates and routes of excretion.