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Insecticides, Organochlorines
Abstract
Few chlorinated organic insecticides remain in use in North America and Europe. Several have been classified as Persistent Organic Pollutants and proscribed globally. However, their considerable benefits to humanity in the past should not be overlooked nor should the lessons that were learned during the period when they were applied to control disease vectors and agricultural pests throughout the world. Organochlorine compounds were not only used as pesticides, but they also had many industrial uses. Chlorinated organic compounds were also byproducts of a number of chemical manufacturing processes, and as a result of the careless disposal and handling of wastes, quantities were applied into the environment.
Endosulfan has been used for over 50 years. Although most analogs have been discontinued, endosulfan has less environmental persistence. Nevertheless, pressure groups are lobbying for a worldwide ban. The reasons are: possible rodent male reproductive toxicity, other endocrine effects and cancer; human epidemiology, and exposure studies; residues appearing in remote areas of the world, e.g., the Arctic.
The endosulfan toxicology database is described and risks of its use assessed.
Endosulfan is an antagonist at the GABA(A) receptor Cl(-) ionophore in mammalian CNS. Rat acute toxicity is moderate, LD(50)=48 (M) or 10 mg/kg/d (F), oral gavage; 130 (M), 70 mg/kg/d (F) dermal; LC(50)=34.5 microg/L (M), 12.6 microg/L (F), inhalation. Critical NOELs for risk assessment: acute oral (gavage)=0.7 mg/kg/d (rabbit developmental); Subchronic oral (diet)=1.2 mg/kg/d (rat reproduction); Chronic oral (diet)=0.6 mg/kg/d. There were no acceptable dermal toxicity studies. The critical acute and subchronic inhalation NOELs=0.001 mg/L, chronic inhalation=0.0001 mg/L (estimated). Toxicity to rat sperm occurred at doses causing neurotoxicity. Endocrine effects, resulting from P450 oxygenase(s) induction, were reversible. Increased cancer, genotoxicity, or histopathology in rodents was not observed in any organ. Possible effects on brain biogenic amine levels were probably secondary.
Epidemiology and rodent studies suggesting autism and male reproductive toxicity are open to other interpretations. Developmental/ reproductive toxicity or endocrine disruption occurs only at doses causing neurotoxicity. Toxicity to the fetus or young animals is not more severe than that shown by adults.
This chapter describes aspects of the known toxicity of chlorinated insecticide dichlorodiphenyltrichloroethane (DDT) and its analogs such as methoxychlor. The chapter summarizes the acute toxicity of DDT to common laboratory animals. It may be concluded that dissolved DDT is absorbed by all routes, although DDT powder is absorbed through the skin to only a negligible degree. There is virtually no sex difference in the acute toxicity of DDT to rats. Toxicity data indicate that respiratory exposure to DDT is of no special importance. The absorption of DDT from the gastrointestinal tract is slow. Whereas intravenous injection at the rate of 50 mg/kg produces convulsions in rats in 20 minutes, convulsions occur only after 2 hours when DDT is administered orally at a rate two or more times the LD 50 value. DDT is stored in all tissues the highest concentrations of DDT usually being found in adipose tissue. Rats store DDT in their fat at all measurable dietary levels including trace concentrations. The major toxic action of DDT is clearly on the nervous system, probably by slowing down closing of axon sodium channels. DDT has been shown in vitro and sometimes in vivo to influence some enzymes of intermediary metabolism and other miscellaneous enzymes.
This chapter explores the pentachlorophenol and its uses, absorption, and case reports. Pentachlorophenol is commonly abbreviated as PCP and is also known as penta, chlorophen, penchlorol, pentachlorofenol, and pentachlorofenolo. PCP, in common with other chlorophenols, has a broad range of biocidal activity. In particular, PCP has been found to be effective as an algicide, bactericide, fungicide, herbicide, insecticide, and molluscicide. Pesticidal use of PCP is regulated at the federal level under the Federal Insecticide, Fungicide, and Rodenticide (FIFRA). It is permitted to use PCP as a biocidal agent on wood, but not on wood to be used for log homes. It is also permitted to use PCP as a biocide in oil field flood waters and in pulp. PCP is readily absorbed by oral, inhalation, and dermal routes of exposure. The case report literature on the toxicity of subchronic exposures to PCP is primarily indicative of hemotoxicity. In one of the cases of aplastic anemia, the patient had handled wet lumber processed with a commercial product containing 3% PCP and 1.5% tetrachlorophenol; handling resulted in dermal and oral (hand-to-mouth) exposure to the wood preservative. The patient died of related causes 5 months after clinical onset.
The photodegradation of DDT in water was examined with a high-pressure mercury lamp. A total of 17 photodegradation products of DDT including DDD, DDE and DDMU were identified by gas chromatography-mass spectrometry (CC-MS). Mass spectrometric analyses were done with electron impact (EI), methane positive chemical ionization (PCI) and electron capture negative ion chemical ionization (ENCI). The degradation rate of DDT in the presence of acetone was measured against the irradiation time. After the irradiation for 10 min, 80% of DDT was converted into a number of products, including DDD, DDE, DDMU and dichlorobenzophenone, through reductive dechlorination, oxidation, isomerization and chlorination. On the basis of the identified products, the photodegradation pathways of DDT are proposed.
To investigate the degradation process of DDT
(2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane) in a system in strong
putrefaction, one litre of activated sludge was fed with 100 mg of p,
p'-DDT, fortified with 14C-DDT (5 µCi), and containing
DDD (2,2-bis-(p-chlorophenyl)-1,1,1-dichloroethane, 4.0%) and DDE
(2,2-bis-(p-chlorophenyl)-1,1-dichloroethylene, 3.1%) as contaminants.
The herbicide, pentachiorophenol decomposes within a few weeks after its application in rice fields. A reductive dechloronation was revealed as one of its decomposition pathways, in which some microorganisms play a dominant role and other soil chemical factors in a reduced condition are relatively of little importance. The stable decomposition products found in the paddy soil were 2, 3, 4, 5-, 2, 3, 5, 6- and 2, 3, 4, 6-tetrachlorophenol, 2, 4, 5- and 2, 3, 5-trichlorophenol, 3, 4- and 3, 5-dichlorophenol, and 3-chlorophenol.
Pyrethroids are divided into two classes (Types I and II) based on their effects on the cercal sensory nerves recorded in vivo and in vitro and on the symptomology they produce in dosed cockroaches, Periplaneta americana. Type I compounds include pyrethrins, S-bioallethrin, [1R,cis]resmethrin, kadethrin, the 1R,trans and 1R,cis isomers of tetramethrin, phenothrin, and permethrin, and an oxime O-phenoxybenzyl ether. Electrophysiological recordings from dosed individuals reveal trains of cercal sensory spikes and sometimes also spike trains from the cercal motor nerves and in the CNS. Low concentrations of these pyrethroids act in vitro to induce repetitive firing in a cercal sensory nerve following a single electrical stimulus. This in vitro measurement, standardized for evaluating structure-activity relationships, shows that only 1R, insecticidal isomers are highly effective neurotoxins. The most potent compounds on the isolated nerve are [1R,trans]- and [1R,cis]tetramethrin, each active at 3 × 10−13M. The poisoning symptoms of Type I compounds are restlessness, incoordination, hyperactivity, prostration, and paralysis. Type II compounds include [1R,cis,αS]- and [1R,trans,αS]cypermethrin, deltamethrin, and [S,S]fenvalerate. These α-cyanophenoxybenzyl pyrethroids do not induce repetitive firing in the cercal sensory nerves either in vivo or in vitro; moreover, they cause different symptoms, including a pronounced convulsive phase. Two other pyrethroids with an α-cyano substituent, i.e., fenpropathrin and an oxime O-α-cyanophenoxybenzyl ether, are classified as Type I based on their action on a cercal sensory nerve but the symptoms with these compounds resemble Type II. The two classes of pyrethroid action evident with the cockroach are discussed relative to their neurophysiological effects and symptomology in other organisms.
An in-depth evaluation of the potential for microorganisms to remove anthropogenic organic compounds, mainly priority pollutants and related compounds, is presented. The evaluation indicates that use of properly selected populations of microbes, and the maintenance of environmental conditions most conducive to their metabolism, can be an important means of improving biological treatment of organic wastes. One major theme is that microorganisms not normally associated with biological waste treatment have potential advantages when the removal of anthropogenic compounds is the goal. An extensive summary of examples of anthropogenic compounds and microorganisms that can attack them is presented in tabular form. A second table lists the selective uses of microorganisms for removal of different anthropogenic compounds. (KRM)
Die Bildung von α - HCH aus Lindan wurde erstmals an pflanzlichem Material nachgewiesen. Die Identifizierung des α - HCH erfolgte sowohl gaschromatographisch als auch massenspek-trometrisch.
Die aus dem Lindan gebildete α - HCH-Konzentration erreichte nach 6monatiger Versuchszeit einen Wert von 0, 046 ppm. Der Wirkstoff Lindan stellt daher - zusätzlich zu den industriell hergestellten α - HCH-Mengen- eine beachtliche Kontaminationsquelle für das α - HCH in der Ökosphäre dar.
1.1. Water-soluble small-molecule phosphate compounds were identified in red cells of a hag-fish, Eptatretus stoutii, and a lamprey, Entosphenus tridentatus, representatives of the two subclasses of cyclostomes.2.2. The concentration of ATP was high in red cells of some hagfish and low in others, while ADP remained high, a possible protection for the animals during periods of severe hypoxia.3.3. A new as yet unidentified strongly u.v.-absorbing non-phosphate compound, discovered in the hagfish red cell, had a high concentration estimated to be about 10 millimolar.4.4. A large fraction of the total phosphate of the lamprey red cell was in the form of adenine mononucleotides with a high ratio of ATP to ADP and of ADP to AMP.5.5. A remarkable finding in the lamprey red cell was the presence of a substantial pool of 2,3-diphosphoglycerate, a compound absent from the hagfish and not previously found in red cells of any of the true fishes.6.6. Neither hagfish nor lamprey had any inositol polyphosphates in their red cells and both had small pools of GTP.7.7. There were interesting differences in morphology between red cells of hagfish and lamprey and between the two and other vertebrates.
1.Rates of p-nitrophenyl alkyl ether O-dealkylation in male and female mice and flies were found to vary with chain length in the following order: house flies, methyl > ethyl > n-propyl > n-butyl; flesh flies, methyl = ethyl > n-propyl > n-butyl; mice, ethyl > methyl > n-propyl > n-butyl.2.In all species, methoxychlor was O-dealkylated at a greater rate than ethoxychlor, and ethoxychlor was the most toxic analogue.3.In vivo activity correlated in order of magnitude with in vitro microsomal O-dealkylation in all cases.4.In vitro differences in activity were reduced at higher substrate concentrations, and evidence is presented to indicate the presence of both high affinity and low affinity enzymes (or active sites) which act on the same substrates.
WE report the formation of bis(p-chlorophenyl)acetonitrile, (p, p' - DDCN) together with 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (p, p'-TDE) and other products from 1,1,1-tri-chloro-2,2-bis(p-chlorophenyl)ethane (p, p'-DDT) in the presence of biologically-active anaerobic sewage sludge.
The effects of an acute dose of p,p′-1,l,1-trichloro-2,2-bis (p-chlorophenyl)ethane (p,p′-DDT) have been investigated on the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase in rat liver. Administration of p,p′-DDT (600 mg/kg, p.o.) produced 2- to 2.5-fold stimulation of these key gluconeogenic enzymes in 5 hr, although statistically significant increases could be detected at 1 hr. Blood glucose increased as early as 0.5 hr, attained peak values at 1 hr, and then declined to reach control levels m 3–5 hr. In contrast, hepatic glycogen decreased gradually to 47 per cent of the control values in 1 hr, and was restored by 3 hr following treatment with this insecticide. Administration of p,p′-DDT to adrenalectomized rats produced similar changes in blood glucose and hepatic glycogen, suggesting that the insecticide-induced hyperglycemia and glycogenolysis may not be mediated by a release of catecholamines from the adrenals. Doseresponse studies revealed that 100 mg/kg of p,p′-DDT was the minimal amount necessary to induce statistically significant increases in the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. Maximal stimulation of the four key gluconeogenic enzymes was seen generally at 5 hr when rats were treated with a 400–600 mg/kg dose of p,p′-DDT. Daily administration of small doses of p,p′-DDT (5 or 25 mg/kg) for 45 days also resulted in significant enhancement in the activities of various hepatic gluconeogenic enzymes. Actinomycin D, cycloheximide or ethionine failed to affect the basal levels of either of these hepatic enzymes, but effectively reduced the insecticide-induced increases in various enzyme activities. Treatment of adrenalectomized rats with p,p′-DDT enhanced various hepatic enzymes to a degree similar to that observed in intact animals. Furthermore, administration of triamcinolone to p,p′-DDT-treated adrenalectomized rats did not potentiate the action of the insecticide on any of the gluconeogenic enzymes examined. Our results suggest that treatment with p,p′-DDT produces marked increases in the quartet of key, rate-limiting gluconeogenic enzymes in hepatic tissue which are not mediated through a release of corticosteroids from adrenal glands.
Photochemical reactions of tetra-, penta-, and hexachlorobenzenes in the presence and absence of acetone as sensitizer at wavelengths GAMMA 285 nm have been studied. The reductive dechlorination is the main photochemical pathway in both sensitized and nonsensitized photolyses. 1,2,4-Trichlorobenzene appears as the main photoproduct of the nonsensitized photolyses of 1,2,3,5-tetrachlorobenzene, while the major photoproduct of the sensitized irradiation of this substrate is 1,3,5-trichlorobenzene. The nonsensitized photoreactions of tetrachlorobenzenes yield photoisomerized chlorobenzenes and also give product chlorobenzenes containing more chlorine atoms than the starting material. Yields of up to several percent of polychlorobiphenyls (PCBs) are obtained in the case of sensitized irradiation of tetra- and pentachlorobenzenes, but this reaction is less significant in the case of direct photolysis. 30 references.
The pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane] and its metabolite DDE [ 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene] can be photoOxidized in methanol. Photolytic generation of free radicals that may abstract hydrogen
from solvent, react with oxygen, or abstract hydrogen from unreacted substrate occurs. Further decomposition of short-lived
intermediates yields many compounds. Oxidation products include benzoic acids, aromatic ketones, and chlorinated phenols.
The DDE also undergoes photocyclization to give dichlorofluorene derivatives.
Because of the wide use of the persistent insecticide benzene hexachloride (BHC), its residues have been found in soils, plants, animals, and foods. From the viewpoint of environmental toxicology, the principle residue problem of BHC is that particular isomes, such as α and β, but not the active γ isomer accumulate in food. In this study, the authors investigate the metabolic fate of γ BHC in the environment. Highly purified γ BHC was incubated with aquatic sediments under simulated natural conditions and with a soil microorganism under laboratory conditins. Non radioactive γ BHC used throughout the study contained 0.0017% of impurity as α BHC. The results demonstrate that α BHC can be isolatedfrom the environment in quantities larger than those expected as the basis of selective accumulation of impurities from the starting product alone. The cause of the transformation of γ BHC to α BHC in the environment could be micribial, for laboratory studies have shown that a microorganism could indeed convert γ BHC to α BHC particularly when he medium is enriched with NAD. The significance of this work is that it as been demonstrated for the first time that microorganisms in pure culture can isomerize γ BHC. As their is no document to indicate the presence of this tye of isomerization mechanism in the chemical or biologica fields, further studies are warranted.
The degradation of methoxychlor (14C‐ring‐labelled) was studied under laboratory conditions in Take and pond sediments (water‐sediment ratio, 10–20:1) incubated under various redox conditions at 22.5 or 10°C. Methoxychlor degraded rapidly in sediments with half‐lives of <28 days under nitrogen aeration (Eh < ‐50 mv), 49 to 55 days under static aerobic ¿onditions and 115 to 206 days in air‐purged flasks (Eh 220 to 464 mv). The major degradation products were dechlorinated methoxychlor (DMDD) and mono‐ and dihydroxy (demethylated) derivatives of methoxychlor and DMDD. Dihydroxy‐ derivatives represented 15% of extractable radioactivity in pond sediments and 28% in lake sediments after 148 days of aerobic incubation. Under nitrogen aeration, mono‐and dihydroxy‐derivatives represented 44 to 65% of extractable 4C after 28 days incubation.
4-Chloro-, 2,4-dichloro-, 3,4-dichloro-, 2,3,5-trichloro-, and 2,4,5-trichlorophenylmercapturic acids were identified as main metabolites of lindane, γ-isomer of 1,2,3,4,5,6-hexachloro-cyclohexane, in rat urine. Pathways to these metabolites were shown to include as the most important intermediary metabolite. and also seem to be involved in these pathways, while plays a minor role in the pathway. Glutathione conjugation, using the rat liver soluble fraction, occurred directly on the polychlorocyclohexenes, not on their further transformed products. In in vivo biodegradation, may be dechlorinated and dehydrochlorinated at the endoplasmic reticulum before it undergoes the glutathione conjugation in cytosol, although other polychlorocyclohexenes generally react in a manner similar to that in the in vitro reaction.
Paralysis of fifth stage larvae of Rhodnius caused by treatment with chlorinated hydrocarbon, organophosphorus, methylcarbamate, pyrethroid, and other types of insecticide chemicals leads to rapid secretion by their Malpighian tubules. As a result, there is in each case a very large increase in the volume of rectal fluid and a corresponding reduction in the hemolymph volume. The mode of action appears to involve the liberation of a diuretic factor, probably the diuretic hormone, from the central nervous system into the hemolymph at the paralytic stage of poisoning. The disturbances in water distribution and cation balance resulting from insecticide-induced diuresis possibly contribute to the eventual death of treated insects.
The persistence of the γ isomer of benzene hexachloride (lindane), when added to submerged tropical soils at a rate approximately three times that recommended for the protection of rice from stem borer infestation and of the α, β, and δ isomers of benzene hexachloride applied at similar rates was between 70 and 90 days. Losses of all four isomers from sterilized, flooded soil samples were much slower than from nonsterilized samples, indicating that the microflora of submerged soils is able to degrade benzene hexachloride. Microbial degradation of γ-BHC was demonstrated by the release of C14O2 from submerged soils treated with C14-labeled γ-BHC. An application of γ-BHC at a rate approximately five times the usual field rate apparently inhibited CO2 evolution from two tropical soils.
After application of pentachlorophenol-14C at 23 kg/ha to flooded rice soil in a plant growth chamber, 36.5% was recovered in soil after one growing period and 30.1% after two periods. After one growing period, the residues were 28.61% unidentified unextractable substances, 0.51% unchanged free pentachlorophenol, 0.61% conjugated pentachlorophenol, 1.67% free tetra- and trichlorophenols, <0.01% conjugated trichlorophenols, 0.33% anisoles, and 4.74% highly polar, mostly nonhydrolyzable compounds (percent of applied radioactivity). In the second growing period, the portion of unextractable residues in soil increased; the composition of the extractable radioactivity was similar to that of the first vegetation period.
Chlordane is an environmentally persistent soil insecticde, particularly useful in the protection of wooden structures from termite damage. A slow change was found to occur in the composition of soil residues of technical chlordane, suggestive of chemical or biological transformation of certain components. An actinomycete (Nocardiopsis sp.) isolated from soil was capable of extensively degrading chlordane in pure culture. Growing broth cultures of Nocardiopsis metabolized pure cis- or trans-chlordane to at least eight solvent-soluble substances including dichlorochlordene, oxychlordane, heptachlor, heptachlor endo-epoxide, chlordene chlorohydrin, and 3-hydroxy-trans-chlordane. Identifications were based on gas chromatographic or mass spectroscopic analysis. Oxychlordane was metabolically inert, and accumulated in the mycelium as a terminal residue. Patterns of metabolic activity in microorganisms were compared to the residue patterns in chlordane-treated soil.
A study was made to determine the fate of fluorine in the production of wet-process phosphoric acid and to explore methods of effective pollution control. Results indicated that the quality of the acid is improved by precipitation of the metallic impurities as complex fluoride compounds, and up to 85% of the fluorine can be immobilized as an insoluble compound in the by-product gypsum solids. Twelve different fluorine compounds were identified as possible precipitates in the production of wet-process phosphoric acid. Fluorite and chukhrovite were sufficiently insoluble in aqueous solutions to suggest long-term storage in gypsum ponds without undergoing reactions that will release fluorine to the atmosphere or natural waters.
The fate of DDT present in ensiled pasture herbage has been studied in laboratory silos of 2 kg capacity. The DDT was extensively decomposed in the process, but the accumulation of equally objectionable degradation products, identified as pp-DDD gave a net reduction of about 50%. These changes appeared to be unrelated to the type of silage fermentation that ocuurred. The results suggest enbsilage to be a useful management procedure in dealing with DDT-contaminated pasture.
Some effects of DDT on the cockroach nervous system have been correlated with poisoning symptoms, using free-walking cockroaches with implanted electrodes. Experiments at 16.5°C and 32°C used LD95 doses and at 25°C, an estimated LD95. DDT had excitant actions on each nerve studied; cercal afferent and efferent neurones, and abdominal interneurones. The effects on the central nervous system became more marked as temperature was reduced, despite the smaller quantity of DDT employed, but the excitant actions on the peripheral nervous system were not quantified. It is suggested that the effects of DDT on the cockroach nervous system could account for the negative temperature coefficient of toxicity of DDT.
The action of allethrin has been studied in the free-walking cockroach, Periplaneta americana (L) using implanted electrodes, at 15 and 32°C, following topical application of an LD95 dose (that at 32°C being approximately ten times the LD95 at 15°C). At both temperatures there was marked hyperexcitation of the peripheral nervous system. At 32°C there was also hyperexcitation of the central nervous system but central effects at 15°C were probably secondary. Likewise, nerve blockage often did not occur until many hours after paralysis and could thus be a secondary consequence of allethrin poisoning.
This paper describes a technique enabling the mode of action of insecticides to be followed using a free-walking cockroach. The nervous effects can be followed over a period of days, using the same individual insect. Information can be obtained concerning the central nervous system, a sensory nerve, and the synapses between them.
The current investigation was designed to determine if the pesticide methoxychlor (M) mimicked the effects of estrogen in the brain and on behavior. Running wheel activity (RWA) and sex behaviors were evaluated in this study because the role of estrogen in the regulation of these behaviors has been thoroughly established. M exposure at 400 mg/kg/day (90% pure) induced high levels of acyclic RWA and persistent vaginal estrus in the female rats. Following ovariectomy (ovx), RWA declined precipitously in controls but remained at high levels in M-treated-ovx females. M also produced estrogen-like alterations of the uterine endometrial epithelium, the ovary, and growth after ovx. In another study, ovx female rats were dosed with M at 200 mg/kg/day and then with progesterone (P). P acts as an antiestrogen and specifically suppresses estrogen-induced RWA. P blocks the synthesis of estrogen receptors in the CNS and reproductive tract but does not lower RWA induced by nonestrogenic mechanisms. After 14 days of M administration RWA was increased fourfold over the ovx-oil-treated females. Subsequently, P injections reduced RWA levels far below those seen when the ovx-M-treated rats were injected with oil. The P-induced decline represents a 95% inhibition of the M-induced increase in RWA. Subsequently, M-treated-ovx rats and hamsters were injected with P and tested for their ability to display reproductive behaviors when paired with a stud male. Female sexual behaviors are induced by the administration of estrogen followed by progesterone. In this study the M-treated females displayed reproductive behaviors, in contrast to the oil-treated rats and hamsters. The observation that the high levels of RWA induced by methoxychlor treatment in ovx rats can be suppressed by concurrent progesterone injections demonstrates that the increase in RWA is due to the estrogenic effects of methoxychlor on the CNS. The fact that methoxychlor, followed by P injections, induces behavioral estrus in the rat and hamster extends this estrogenicity to other areas in the CNS.
Poisoning of adult Schistocerca gregaria leads to the release of the hyperglycaemic and adipokinetic factors from the corpus cardiacum. The mode of action appears to involve the liberation of hormones at the paralytic stage of poisoning in amounts greater than that released normally. Behavioural changes and disturbances in metabolism resulting from insecticide-induced hormone release possibly contribute to the eventual death of treated insects.
The effect of soil water content on the fate of applied 14C labelled 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (pp′-DDE) was examined over a 42 day period in laboratory microcosm experiments. Residues released as CO2 and volatiles during the experiments were measured, as were acetone/hexane extractable and unextractable (bound) residues at the conclusion of the experiments. Release of 14CO2 was low (>0.7% of added label) under unflooded conditions and virtually zero from flooded soil. Autoclaving soil prior to the experiment essentially eliminated 14 C02 release. In unflooded, unautoclaved treatments mean binding of pp′-DDT and pp′-DDE ranged between 6.7 and 9.7%. Increased binding of pp′-DDT (24.5%) and pp′-DDE (11.5%) was observed under flooded unautoclaved conditions. Reducedp,p′-DDT binding was observed where flooded soil was autoclaved prior to the experiment. Flooding soil containing 14C-pp′-DDT resulted in considerable accumulation of labelled pp′-DDD, demonstrating the capacity within the soil for this transformation, and suggesting that the absence of relatively rapid DDT degradation via pp′-DDD is due to prevailing conditions, rather than the lack of degradative capacity within the microbiota.
In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and > or = 1-fold, respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51 microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or = 2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners.
1.
A major metabolite of hexachlorocyclohexane (HCH) in rats, 2,4,6-trichlorophenol (2,4,6-TCP), is shown to accumulate in suspensions of rat liver microsomes incubated with HCH in the presence of NADPH and air. Evidence is presented for the involvement of cytochrome P-450. The rate of formation of 2,4,6-TCP differed for different configurations of HCH in an order corresponding roughly to that seen in vivo when daily urinary output of 2,4,6-TCP was estimated after i.p. application of HCH.
2.
A reaction sequence is proposed for the formation of 2,4,6-TCP from HCH assuming hydroxylation to be the initial step. The sequence would explain the exclusive formation of symmetrical TCP obtained in vitro with the HCH-configurations alpha, beta, delta and epsilon. Chemical evidence supporting the hypothesis is included as is the result of experiments, both in vivo and in vitro, with isomers of pentachlorocyclohexene and of trichlorobenzene which excluded dehydrochlorination of HCH as the initial reaction. In addition, the differences which exist between isomers of HCH in the accessibility of carbon-hydrogen bonds are shown to provide a reasonably consistent explanation of the differences in rate recorded in vitro for their conversion to 2,4,6-TCP.
3.
Gamma-HCH, in contrast to its isomers, was found to be converted by NADPH-substituted rat liver microsomes to several chlorophenols. Second in quantity to 2,4,6-TCP was a tetrachlorophenol, presumably the 2,3,4,6-isomer, which is known to be a prominent metabolite of gamma-HCH in rats. Evidence has been obtained which indicates that the formation of 2,4,6-TCP from gamma-HCH in vitro is largely independent of that of 2,3,4,6-tetrachlorophenol. It is suggested that the formation of the tetrachlorophenol may be the result of hydroxylation of the hexachlorocyclohexene which has recently been shown by others to be formed from gamma-HCH in a reaction involving cytochrome P-450.
4.
With reference to similarly specific recognition by constituents of nervous tissue, the distinctive transformation, by hepatic enzymes, of HCH of the gamma-configuration is considered as to its cause by invoking the well known fact that gamma-HCH, unlike its isomers, undergoes ring inversion at ordinary temperatures.
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.
Photodecomposition of hexachlorobenzene exposed to sunlight as a crystalline material or on silica gel was extremely slow and no photodecomposition products were identified. This photodecomposition was sensitized by diphenylamine, but not by benzophenone. Photolysis in methanol or hexane with light of wavelengths greater than 260 or 220 nm, respectively, was rapid and the anticipated products of reductive dechlorination (pentachlorobenzene and tetrachlorobenzene) were obtained in each case. In addition, an unexpected photochemical reaction between hexachlorobenzene and methanol resulted in the formation of small amounts of pentachlorobenzyl alcohol and traces of another photoproduct that was probably a tetrachlorodi(hydroxymethyl)benzene.
The metabolic fate oftrans-nonachlor and heptachlor in rats was studiedin vivo andin vitro by using microsomal preparations of the liver. Duringin vivo studies the rate of excretion into urine and feces was monitored. The major metabolic products were collected from the feces and their chemical structures were determined by using various chromatographic and spectroscopic techniques. The immediate major metabolic product oftrans-nonachlor istrans-chlordane which is further converted to 1,2-dichlorochlordene and to oxychlordane. From the latter metabolite, two major stable products, 1-hydroxy-2-chlorochlordene and 1-hydroxy-2-chloro-2,3-epoxy-chlordene are formed. Another route of metabolism is a direct formation of chlordene chlorohydrin which acts as a precursor for 1,2-trans-dihydroxydihydrochlordene. The major metabolic products of heptachlor were heptachlor epoxide, 1-exo-hydroxyheptachlor epoxide and 1,2-dihydroxy-dihydrochlordene.
As a result ofin vitro studies, it was established that the human liver has relatively little capability in convertingtrans-nonachlor totrans-chlordane, as compared to the rat liver similarly prepared. Since the livers from these two species showed almost identical degradation abilities fortrans-chlordane itself, the difference is apparently limited to this particular dechlorination step. The finding is consistent with the phenomenon thattrans-nonachlor accumulates in humans, but not in rats.
Organochlorine pesticide concentrations in blood and various clinical test variables were measured in 2,620 pesticide-exposed
subjects and in 1,049 persons not occupationally exposed to pesticides. Differences in the pesticide contents of blood were
identified in relation to geography, age, and occupational exposure. Analysis of hematologic and biochemical variables in
terms of broad occupational categories revealed only very limited differences, but relationships of certain biochemical tests
to serum organochlorine pesticide contents suggested subtle effects of these pesticides on liver function.