Investigations into mechanisms responsible for seizures induced by chlorinated hydrocarbon insecticides: the role of brain ammonia and glutamine in convulsions in the rat and cockerel

Abstract— Seizures were produced in adult female rats and in cockerels (Gallus domesticusL.) after the intracarotid administration of four structurally-unrelated chlorinated hydrocarbon insecticides. The temporal relationship of the course of the convulsions to levels in whole brain of ammonia and glutamine was examined. High levels of brain ammonia occurred in rats and cockerels poisoned acutely with lindane, dieldrin, heptachlor and DDT. The intensity of convulsions and other neurological signs coincided with and were directly correlated with the increases in brain ammonia, whereas interictal periods were associated with decreased levels of ammonia. In both species the order of drug toxicity was lindane > dieldrin > heptachlor > DDT. Significantly elevated levels of brain glutamine were induced in the cockerels after administration of all four insecticides. In contrast, increased levels of glutamine in rats were found only in those intoxicated with lindane and dieldrin. Although the ammonia-binding mechanism (conversion of free ammonia into glutamine) was saturated throughout the experiments in both the rats and cockerels, the latter were more resistant to ammonia toxicity by virtue of being able to convert free ammonia into glutamine more efficiently than rats. These data, together with data reported by others, lead to the conclusion that the four structurally-unrelated chlorinated hydrocarbon insecticides probably induced convulsions in both species by a common mechanism, involving interference with the production and/or utilization of ammonia.     

Comparison of two techniques for quantifying environmental contaminants in human serum

Peak area matching and linear regression were used to quantify eight chlorinated pesticides and polychlorinated biphenyls (as Aroclor 1260) in human serum. There are no statistically significant differences in data obtained by these two quantifying techniques which were indicated by the paired t-test. For chlorinated pesticides, p = 0.053-0.62, and for polychlorinated biphenyls (as Aroclor 1260), p = 0.64. Analyte residues for the chlorinated pesticides ranged from 0.5 ppb for hexachlorobenzene (HCB) to 186 ppb for dichlorodiphenyldichloroethylene (DDE). Analyte residues for the polychlorinated biphenyls (as Aroclor 1260) ranged from 5-114 ppb. The absolute mean percent difference between the two quantifying techniques ranged from 0.06% for DDE to 8.06% for dieldrin (HEOD) among the chlorinated pesticides. The absolute mean percent difference between the two quantifying techniques for the polychlorinated biphenyls (as Aroclor 1260) was 3.4%. Peak area matching and linear regression were found to be comparable for quantifying these environmental residues in serum when the following conditions apply: 1) the concentration of the chlorinated pesticides is greater than or equal to 0.5 ppb (e.g., HCB, hexachlorocyclohexane (HCCH), oxychlordane (OC), heptachlor epoxide (HE), transnonachlor (TN), HEOD, and dichlorodiphenyltrichloroethane (DDT); 2) the concentration of the chlorinated pesticide is greater than or equal to 3 ppb (e.g., DDE); and 3) the total concentration of polychlorinated biphenyls (e.g., as Aroclor 1260) is greater than or equal to 5 ppb.     

A Preliminary Human Health Risk Assessment of Organochlorine Pesticide Residues Associated with Aquatic Organisms from the Rangsit Agricultural Area,Central Thailand

Food consumption is one of the main routes of human exposure to organochlorine pesticide residues (OCPRs). To assess the potential health risks associated with OCPRs contaminants due to freshwater organism consumption, a number of vegetables, prawn, snail, and fish were collected from Khlong 7 (canal), Rangsit agricultural area, Pathum-Thani Province, Thailand. The samples were extracted using a multiresidue extraction method and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb) levels. Based on a plausible worst-case scenario, the local population could be at risk for cancer due to consumption of fish contaminated by α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, dieldrin, DDD, DDE, and DDT. Likewise, individuals may be at risk from consumption of Lanchester's freshwater prawn Macrobrachium lanchesteri, freshwater snail Filopaludina mertensi, swamp morning-glory Ipomomea aquatica, neptunia Neptunia oleracea, and water lily Nymphaea lotus because these species all contained elevated concentrations of α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, and dieldrin.     

Degradation of Endrin, Aldrin, and DDT by Soil Microorganisms

Twenty microbial cultures which had been shown to degrade dieldrin were tested to determine their ability to degrade endrin, aldrin, DDT, gamma isomers of benzenehexachloride (gamma-BHC), and Baygon. All isolates were able to degrade DDT and endrin, whereas 13 degraded aldrin. However, none of them was able to degrade Baygon or gamma-BHC.     

Comparative biodegradation of alkyl halide insecticides by the white rot fungus, Phanerochaete chrysosporium (BKM-F-1767).

The ability of Phanerochaete chrysosporium to degrade six alkyl halide insecticides (aldrin, dieldrin, heptachlor, chlordane, lindane, and mirex) in liquid and soil-corncob matrices was compared by using 14C-labeled compounds. Of these, only [14C]lindane and [14C]chlordane underwent extensive biodegradation, as evidenced by the fact that 9.4 to 23.4% of these compounds were degraded to 14CO2 in 30 days in liquid cultures and 60 days in soil-corncob cultures inoculated with P. chrysosporium. Although [14C]aldrin, [14C]dieldrin, [14C]heptachlor, and [14D]mirex were poorly mineralized, substantial bioconversion occurred, as determined by substrate disappearance and metabolite formation. Nonbiological disappearance was observed only with chlordane and heptachlor.     

Comparative biodegradation of alkyl halide insecticides by the white rot fungus, Phanerochaete chrysosporium (BKM-F-1767).

The ability of Phanerochaete chrysosporium to degrade six alkyl halide insecticides (aldrin, dieldrin, heptachlor, chlordane, lindane, and mirex) in liquid and soil-corncob matrices was compared by using 14C-labeled compounds. Of these, only [14C]lindane and [14C]chlordane underwent extensive biodegradation, as evidenced by the fact that 9.4 to 23.4% of these compounds were degraded to 14CO2 in 30 days in liquid cultures and 60 days in soil-corncob cultures inoculated with P. chrysosporium. Although [14C]aldrin, [14C]dieldrin, [14C]heptachlor, and [14D]mirex were poorly mineralized, substantial bioconversion occurred, as determined by substrate disappearance and metabolite formation. Nonbiological disappearance was observed only with chlordane and heptachlor.     

Risk Assessment for Dermal Exposure of Organochlorine Pesticides for Local Fishermen in the Rangsit Agricultural Area,Central Thailand

Organochlorine pesticides (OCPs) used in agriculture and for public health purposes were banned in Thailand over the past decade; however, their persistent residues have been found in several agricultural areas of the country. This may result in adverse effects to human populations. This study investigated the concentration of organochlorine pesticides residues (OCPRs) in surface water and evaluated the potential cancer risk associated with dermal contact of the local fisherman fishing in the Khlong 7 canal, Rangsit agricultural area, central Thailand. Water samples were extracted using liquid-liquid extraction (LLE) and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb or ng/ml) levels, that is, ∑ Endosulfan (α -, β -, and -sulfate) 0.082 ng/ml > DDT and derivatives 0.019 ng/ml > ∑ HCH (α -, γ -, β -, and δ -HCH) 0.014 ng/ml > aldrin and dieldrin 0.007 ng/ml > heptachlor and heptachlor epoxide 0.0068 ng/ml > endrin and endrin aldehyde 0.005 ng/ml > methoxychlor 0.001 ng/ml, respectively. Using the worst-case scenario defined as the reasonable maximum exposure (RME) to assess the potential cancer risk, five OCPs (dieldrin, 4,4′ -DDT, β -HCH, heptachlor, and heptachlor epoxide) may pose a risk of concern on a lifetime human carcinogenesis greater than one in a million.     

Studies on the resistance to various insecticides of a house fly strain (Diptera: Muscidae) selected with azamethiphos.

A colony of azamethiphos-resistant house flies, Musca domestica (L.), was obtained from Denmark and further selected in the laboratory with azamethiphos for four generations. LD50s for various insecticides were determined and compared with those of a susceptible house fly strain. The selected flies showed cross-resistance to all insecticides evaluated. The flies were highly resistant to most organophosphorus, carbamate, and chlorinated hydrocarbon insecticides except prothiophos, p,p'-DDT, and the pyrethroids. We conclude that the main mechanisms responsible for resistance are presumed to be factors other than acetylcholinesterase sensitivity and nerve sensitivity due to knockdown resistance.     

The insecticides; their hazard in industry and in the home

Chemical, pharmacologic and toxicologic properties of the chlorinated hydrocarbon and organic phosphate insecticides have been reviewed. The chlorinated group present problems if there is either acute or chronic exposure, whereas the problems associated with the organic phosphates develop only in event of acute exposure. Chlorinated hydrocarbon insecticides accumulate in body fat depots and cause both liver and kidney damage while being metabolized and excreted. Organic phosphates destroy cholinesterase and produce effects related to overstimulation of the cholinergic branch of the autonomic nervous system. Barbiturates control the convulsions produced by the chlorinated hydrocarbon insecticides. Atropine blocks most of the effects of the organic phosphate insecticides. These compounds may be grouped in the following order of decreasing toxicity: TEPP, HETP, parathion, OMPA, ENP, aldrin, chlorophenothane, toxaphene, gamma benzene hexachloride, malathon and chlordane.     

THE INSECTICIDES—Their Hazard in Industry and in the Home Part I—Chemistry and Pharmacology

Chemical, pharmacologic and toxicologic properties of the chlorinated hydrocarbon and organic phosphate insecticides have been reviewed. The chlorinated group present problems if there is either acute or chronic exposure, whereas the problems associated with the organic phosphates develop only in event of acute exposure.Chlorinated hydrocarbon insecticides accumulate in body fat depots and cause both liver and kidney damage while being metabolized and excreted. Organic phosphates destroy cholinesterase and produce effects related to overstimulation of the cholinergic branch of the autonomic nervous system. Barbiturates control the convulsions produced by the chlorinated hydrocarbon insecticides. Atropine blocks most of the effects of the organic phosphate insecticides. These compounds may be grouped in the following order of decreasing toxicity: TEPP, HETP, parathion, OMPA, ENP, aldrin, chlorophenothane, toxaphene, gamma benzene hexachloride, malathon and chlordane.     

Effect of dieldrin and lindane on the growth and nodulation ofVicia faba

The chlorinated hydrocarbon insecticides, dieldrin and lindane, were used at the normal and 20-fold rate. The plants were grown in pots containing clay soil. The results showed that whereas low and high concentrations of dieldrin as well as low concentration of lindane had no effect on the morphological characters of the shoot and root systems, high concentration of lindane had a harmful effect. Nodulation was slightly affected by low and high concentrations of dieldrin as well as low concentration of lindane. High concentration of lindane had a deleterious effect on nodulation.     

Isolation and identification of dieldrin-degrading Pseudonocardia sp. strain KSF27 using a soil-charcoal perfusion method with aldrin trans-diol as a structural analog of dieldrin

We isolated a novel aerobic dieldrin-degrading bacterium from an enrichment culture in a soil–charcoal perfusion system. Enrichment culture using a soil–charcoal perfusion system was an effective way to obtain microorganisms that degrade recalcitrant compounds. The soil–charcoal perfusion was performed using aldrin trans-diol, which was a metabolite of dieldrin. Aldrin trans-diol had higher bioavailability (2.5 mg/l) than dieldrin (0.1–0.25 mg/l), therefore it is possible for microorganisms to utilize it as a substrate in soil. After 100 days of circulation and three exchanges of the medium, the enriched charcoal was harvested and a bacterium isolated. The isolate was designated as strain KSF27 and was found to be closely related to Pseudonocardia spp. as determined by 16S rRNA sequencing analysis. Strain KSF27 degraded aldrin trans-diol by 0.05 μmol/l from an initial concentration of 25.5 μmol/l. The metabolite of aldrin trans-diol was detected by HPLC/MS and determined to be aldrindicarboxylic acid based on retention time and the MS fragment. Moreover, strain KSF27 degraded dieldrin from 14.06 μmol/l to 2.01 μmol/l over a 10-day incubation at 30 °C. This strain degraded dieldrin and other persistent organochlorine pesticides, such as α-endosulfan, β-endosulfan, endosulfan sulfate, heptachlor, heptachlor epoxide and chlordecone.     

Pollution assessment of organochlorine pesticides in urban agricultural soils of Jilin City,China

The content, source, and pollution level of organochlorine pesticides (OCPs) in soils are necessary to assess potential risks to eco-environment and human health, and to target environment-friendly policies. A total of 50 surface soil samples were collected from urban vegetable fields of Jilin City and thirteen OCPs were analyzed. The concentrations were in the ranges of 3.16–48.35 ng·g^?1 for Dichloro-Diphenyl-Tricgloroethanes (DDTs, sum of o, p′-DDT, p, p′-DDT, p, p′-DDD, and p, p′-DDE), 4.37–44.77 ng·g^?1 for Hexachlorocyclohexanes (HCHs, sum of α-HCH, β-HCH, γ-HCH, and δ-HCH), 1.19–13.17 ng·g^?1 for Chlordanes (sum of heptachlor, t-chlordane, and c-chlordane), 0.24–2.60 ng·g^?1 for aldrin, and nd–3.43 ng·g^?1 for dieldrin, respectively. The different compositions indicated that the residues of DDTs and HCHs originated mainly from the historical application, while chlordanes were mostly from recent input. On the basis of soil quality standards of China and the Netherlands, DDTs and chlordanes in this study were categorized as light pollution, and HCHs were classified as no pollution for the majority of soil samples. There are a variety of OCPs residues in urban vegetable soils of Jilin City, but it is still safe and suitable for agricultural production.     

Bacterial bioconcentration of chlorinated hydrocarbon insecticides from aqueous systems

The prevalence of chlorinated hydrocarbon insecticide uptake by chemoorganotrophic bacteria has been investigated. Thirteen bacterial species were observed to sorb and concentrate (bioconcentratc)α-chlordane,β-chlordane, dieldrin, heptachlor epoxide, and lindane from aqueous systems. Bioconcentration, as expressed by the ratio of cellular insecticide in ng/mg (dry wt) to supernatant insecticide in ng/μl, ranged from 10 for lindane byEnterobacter aerogenes to a high of 55,900 forβ-chlordane byCaulobacter vibrioides var.limonus. Amounts of cellular chlorinated hydrocarbon insecticides (CHI) detected and the bioconcentration ratios were observed to have the following order in magnitude:α- orβ-chlordane > dieldrin > heptachlor epoxide > lindane. This decreasing order was the inverse of reported water solubilities for the CHI and the inverse relationship was mathematically defined. The CHI were not easily removed from cells by washing (desorbing) and desorption was directly proportional to insecticide water solubility. Uptake of the CHI was rapid, near-maximum amounts being sorbed within 15 min, and pH 7 appeared optimal for bioconcentration as examined over the range pH 6 to 8. Implications of this investigation are that bioconcentration of CHI by bacteria might serve as a means of introducing these toxic compounds into aquatic food chains and that the bioconcentration phenomenon might lend itself as a treatment procedure for the intentional removal of residual CHI from water supplies and wastewater.     

Time course of metabolism of aldrin and dieldrin by suspension cultures

Time course, up to 100d, of uptake and metabolism of aldrin and dieldrin added at subculture to suspension cultures from Phaseolus vulgaris (French bean) root and shoot, and Solanum tuberosum (potato) tuber comparable, with rapid dieldrin production and delayed appearance of other metabolites. When aldrin and dieldrin not added to Phaseolus cultures until 10 or 20d after subculture usual extent of conversion of aldrin to dieldrin, but reduced production of other metabolites, and growth inhibition negated. Increasing volumes of 2-methoxyethanol had detrimental effect on growth and uptake and metabolism. Dieldrin production maximal during rapid growth phase and probably independent of other conversions.     

THE TOXICITY OF SOME INSECTICIDES TO FIFTH-INSTAR NYMPHS OF THE DESERT LOCUST

The toxicities of the insecticides γ-BHC, diazinon, dieldrin, DNC, heptachlor and parathion to fifth-instar hoppers of the desert locust were determined. Parathion and dieldrin were the most toxic, followed in descending order by heptachlor, γ-BHC, diazinon and DNC. The resistance of the hoppers to γ-BHC and DNC changed appreciably with age within the instar.
The effects of some factors which might influence the resistance of the insects were examined and are discussed.     

In vitro uptake and transfer of chlorinated hydrocarbons among human lipoproteins

The uptake, distribution, and exchange of chlorinated hydrocarbon insecticides (dieldrin and chlordecone) and biphenyls (2,4,5-2',4',5'-hexachlorobiphenyl and 3-chlorobiphenyl) among human lipoproteins was examined by fluorescence quenching, gel filtration, and ultrafiltration. The chlorinated hydrocarbons were rapidly taken up from solution or silica particles by lipoproteins. The distribution of chlorinated hydrocarbons among the lipoproteins was independent of the amount taken up by the lipoproteins. The partition coefficient for each lipoprotein and the serum concentration of individual lipoproteins determined the distribution pattern of chlorinated hydrocarbons among lipoproteins. The chlorinated hydrocarbons attached to albumin or one of the lipoproteins were rapidly transferred to all other lipoproteins. The exchange was complete in less than one minute. The role of rapid exchange of chlorinated hydrocarbons among lipoproteins in removal of these chemicals from blood and distribution to other tissues is discussed.     

Chlorinated hydrocarbons in North Sea whiting (Merlangius merlangus L.), and effects on reproduction. I. Tissue burden and hatching success

Artificially inseminated eggs of feral North Sea whiting (Merlangius merlangus) were incubated in the laboratory in order to determine reproductive success. After incubation, two measures for reproductive success, total hatch and viable hatch, were determined and correlated with chlorinated hydrocarbon residues in the respective ovaries. From their specific toxicities and the sum of all determined chlorinated hydrocarbon contaminants, a contamination factor (CF) was calculated. Significant negative correlations were found between total hatch and DDT, including its metabolites (ΣDDT), dieldrin and the CF. ΣDDT and the CF were also negatively correlated with viable hatch. A threshold value of ovary contamination above which impairment of reproductive success was likely to occur was set at > 200 μg kg⁻¹ wet wt. for ΣPCB, > 20 μg kg⁻¹ wet wt. for ΣDDT and > 10 μg kg⁻¹ wet wt. for dieldrin.     

Isolation of four aquatic streptomycetes strains capable of growth on organochlorine pesticides

Ninety-three wild-type isolates identified as actinomycetes were tested against 11 organochlorine pesticides (OPs): aldrin, chlordane, DDD, DDE, DDT, dieldrin, heptachlor, and heptachlor epoxides, lindane, and methoxychlor. Qualitative screening agar assays displayed 62-78% tolerance of strains to OPs. Four strains designed M4, M7, M9 and M15 were selected based on multi-OP-tolerance, and identified as members of the streptomycetes group. Different growth profiles were observed in cultures of the four selected streptomycetes cultured in synthetic medium containing 5-50 microg x l(-1) aldrin or chlordane or lindane. Increase of aldrin removal by the selected microorganisms was concomitant with the 4.8-36.0 microg x l(-1) pesticide concentration range. After 72 h of streptomycete M7 growth in synthetic medium containing 48.0 microg x l(-1) aldrin, the remaining OP concentration in the supernatant was approximately 10% of the initial concentration. Also, in stationary growth phase less than 2.5 microg x l(-1) aldrin residual concentration was detected in the medium.     

Further mutagenicity studies on pesticides in bacterial reversion assay systems

A total of 228 pesticides (88 insecticides, 60 fungicides, 62 herbicides, 12 plant-growth regulators, 3 metabolites and 3 other compounds) was tested for mutagenicity in bacterial reversion-assay systems with 5 strains (TA100, TA98, TA1535, TA1537 and TA1538) of Salmonella typhimurium and a strain (WP2 hcr) of Escherichia coli. 50 pesticides (25 insecticides, 20 fungicides, 3 herbicides, 1 plant-growth regulator and 1 other compound) were found to be mutagenic. 5 of them required metabolic activation (S9 mix) for their activities. Among various chemical groups, organic phosphates, halogenated alkanes and dithiocarbamates showed higher ratios of mutagens. Although 22 of the pesticides tested have been reported to be carcinogenic, 7 of them, i.e., captain, DBCP, EDB, EDC, ETU, HEH and nitrofen, were detected as mutagens in the present assay. Most of the other 15 non-mutagenic carcinogens were organochlorine pesticides such as alpha-BHC, chlorobenzilate, p,p'-DDT, dieldrin and quintozene.