Renal tubular dysfunction caused by dietary hexachlorocyclohexane (HCH) isomers

Abstract

Dietary administration of β‐ and α‐hexachlorocyclohexane (HCH) to albino rats caused an abnormal excessive excretion of glucose in the urine, blood glucose level being nearly normal. Occurrence of glucosuria was also accompanied by increased excretions of the two low‐threshold compounds ‐ creatinine and urea, their levels in blood being normal. The interference of HCH isomers with renal function as evidenced by biochemical data was also indicated by histopathological lesions observed in the kidney sections, viz., hypertrophy and degeneration of the renal tubular epithelia.     

Understanding fungal potential in the mitigation of contaminated areas in the Czech Republic: tolerance,biotransformation of hexachlorocyclohexane (HCH) and oxidative stress analysis

Environmental Science and Pollution Research - The study of the soil microbial community represents an important step in better understanding the environmental context. Therefore, biological...     

Carcinogenicity of hexachlorocyclohexane (BHC) in pure inbred swiss mice.

Inbred Swiss mice were treated with technical BHC (1) orally with the diet or by intubation and (2) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Symptoms of intoxication in the form of convulsions and tendency of circling in one direction with drooping ears were observed alongwith corneal opacity 40 weeks after the experiment. Oral BHC treatment resulted in a significant increase in the incidence of liver tumours and tumours of lymphoreticular tissue. Males and females were equally susceptible. Skin painting of mice did not significantly increase the incidence of tumour.     

Studies on the distribution of beta- and gamma-isomers of hexachlorocyclohexane in rat tissues

A study of the comparative distribution pattern of beta- and gamma-isomers of hexachlorocyclohexane (HCH) in albino rat tissues as a function of duration of treatment at two dose levels revealed different accumulation patterns for the two isomers in tissues. In general, the accumulation pattern was found to be in the order: fat greater than kidney greater than lungs greater than liver greater than muscle greater than heart greater than spleen greater than brain greater than blood for beta-HCH and fat greater than brain greater than kidney greater than muscle greater than lungs greater than heart greater than spleen greater than liver greater than blood for gamma-HCH. The tissue accumulation of beta-isomer was always greater than that of gamma-isomer in any tissue except in brain. Brain beta-HCH residue levels were relatively lower than in many other tissues except blood, whereas brain gamma-HCH concentration was only next to fat. A higher dose or a longer period of treatment generally produced a more marked elevation of tissue residue levels in beta-HCH fed rats, but not in gamma-HCH treated animals.     

Organo-chlorine pesticide (DDT and HCH) residues in the Taihu Lake Region and its movement in soil-water system I. Field survey of DDT and HCH residues in ecosystem of the region

The use of organo-chlorine (DDT and HCH) has been banned in China for 20 years. A field survey was carried out during 1999-2000 in the Taihu Lake Region. Organo-chlorine pesticide (OCP) residues in soil, water, fish and sediment samples were investigated. DDT was detected in 5 out of 10 samples with concentration ranging from 0.3 to 5.3 microg/kg in the surface (0-15 cm) layer, 6 out of 10 with 0.5 to 4.0 microg/kg in the subsoil layer (16-30 cm), and 4 of 10 with 0 to 2.7 microg/ kg in the deep soil layer (31-50 cm). Results for HCH residues in soil samples were similar to those of DDT. These results indicate that OCP residues in 0-50 cm profile had been leached out or degraded to safe level. In river water DDT was detected in 10 out of 13 samples ranging from 0.2 to 9.3 microg/l, with an average of 1.0 microg/l. While HCH was detected in 12 out of 13 samples ranging from 0.02 to 36.1 microg/l, with an average 5.6 microg/l. DDT residues in sediment ranged from 0.1 to 8.8 microg/kg, while HCH ranged from 0.3 to 66.5 microg/kg. DDT residues in fish body ranged from 3.7 to 23.5 microg/kg and HCH ranged from 3.7 to 132 microg/kg. These results demonstrate an accumulation through food chain (from soil-water-sediment-microbes-crop-fish-... etc.), also that HCH residues are generally more persistent than DDT residues. However, all these data are well below than the state warning standard limit.     

Enantioselective effects of alpha-hexachlorocyclohexane (HCH) isomers on androgen receptor activity in vitro

Alpha-hexachlorocyclohexane (alpha-HCH), a part of the HCH pesticide mixture, is one of the most widespread persistent organic pollutants. Interestingly, only limited number of studies addressed the toxicity of alpha-HCH and the effects of its individual optical isomers have not been investigated in detail. In the present study we separated two alpha-HCH enantiomers by preparative HPLC and studied their activities towards androgen receptor (AR) using the MDA-kb2 cell line stably transfected with the luciferase reporter gene under the control of AR. There was no direct effect of alpha-HCH on AR but both isomers significantly suppressed the activity of AR in co-exposure with the natural ligand dihydrotestosterone in a concentration-dependent manner. One of the enantiomers appeared to be more active at lower concentration, which was also supported by the molecular modeling calculations with AR that showed a slight difference in estimated free energy of binding and inhibition constant between two enantiomers. Although studies with other pesticides demonstrated strong enantioselective differences in toxicity, the present research shows rather minor differences in modulations of AR by both alpha-HCH enantiomers. For the first time, enantioselective effects of alpha-HCH were demonstrated and the results suggest interaction with multiple regulatory events controlling the AR activity. Full elucidation of the toxicity mechanism will require further research.     

Studies on the distribution op β‐ and γ‐isombrs op hexachlorocyclohexane in rat tissues

Abstract

A study of the comparitlve distribution pattern of β‐ and γ‐isomers of hexachlorocyclohexane (HCH) in albino rat tissues as a function of duration of treatment at two dose levels revealed different accumulation patterns for the two isomers in tissues. In general, the accumulation pattern was found to be in the order: fat > kidney > lungs > liver > muscle > heart > spleen > brain > blood for β‐HCH and fat > brain > kidney > muscle > lungs > heart > spleen > liver > blood for γ‐HCH. The tissue accumulation of β‐isomer was always greater than that of γ‐isomer in any tissue except in brain. Brain β‐HCH residue levels were relatively lower than in many other tissues except blood, whereas brain γ‐HCH concentration was only next to fat. A higher dose or a longer period of treatment generally produced a more marked elevation of tissue residue levels in β‐HCH fed rats, but not in γ‐HCH treated animals.

Food restriction subsequent to a period of exposure to dietary β‐ or γ‐HCH caused a mobilization of depot fat without drastic redistribution of the HCH residues stored in it. During food restriction, the residue levels in fat and muscle increased much. The residue levels in brain and other organs were not adversely affected during partial starvation.     

Metabolism of 2-chloro-N-isopropylacetanilide (propachlor) in the rat.

Eleven urinary metabolites from [14C]propachlor were either identified or characterized by mass spectrometry. Those identified were 2-[S-(N-acetyl)cysteinyl]-N-isopropylacetanilide, 2-(methylsulfonyl)-acetanilide, 4'-hydroxy-2-(methylsulfonyl)-acetanilide, and 4'-hydroxyacetanilide. Those characterized were N-(1-hydroxyisopropyl)-2-(methylsulfonyl) acetanilide and its glucuronide, the glucuronides of 4'-hydroxy-N-isopropyl-2-(methylsulfonyl)acetanilide, N-(1-hydroxyisopropyl) aniline, 4'-hydroxy-2-(methylsulfonyl)acetanilide, and either N-(1-hydroxy-isopropyl) acetanilide or 2-hydroxy-N-isopropylacetanilide.     

Reproductive effects of tris(4-chlorophenyl)methanol in the rat.

Tris(4-chlorophenyl)methanol (TCPM) is a global contaminant of unknown origin that is structurally related to the endocrine modulating pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and Dicofol. Therefore, the potential reproductive toxic effects of TCPM were investigated in sexually mature male Sprague Dawley rats (n = 20) treated with 1.0, 10.0 or 100 ppm of TCPM mixed in the diet for 28 days. The calculated TCPM intake was 0.0, 0.1, 1.2 and 12.4 mg/kg/day, respectively. Serum concentrations of follicle stimulating hormone (FSH) in terminal blood samples were significantly (P < 0.02) elevated in the highest dose group compared to the controls. In contrast, dietary exposure to TCPM had no effect on circulating levels of luteinizing hormone (LH), testosterone (T) and the T/LH ratio. Incubation of MCF-7 cells with increasing concentrations of TCPM failed to either induce proliferation or to block the proliferative effect induced by estradiol indicating that TCPM is neither estrogenic or anti-estrogenic. Relative binding affinity studies using androgen receptors from the prostate revealed that TCPM has a binding affinity comparable to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), the principle metabolite of DDT. In addition, the calculated Ki (0.62 microM) for TCPM is lower than the reported Ki's for the antiandrogenic pesticides p,p'-DDE and vinclozolin. Although TCPM binds with the androgen receptor in vitro, the absence of both an effect on serum T levels and morphological changes in the testis suggests that the mechanism of action for elevated FSH levels seen in vivo may not involve an antiandrogenic effect of TCPM at the dose level used in this study. The no adverse effect level for reproductive effects of TCPM is 10 ppm which is equivalent to a calculated intake of 1.2 mg/kg/day.     

A long-term study of vitamin A and polychlorinated hydrocarbon levels in otters (Lutra lutra) in south west England

This paper presents the levels of metals and other trace elements measured in feathers of laggar falcons, Falco biarmicus jugger, in Pakistan. The laggar falcon is resident or locally migrant throughout the Indian Subcontinent where it is a rare and declining species. Breast feathers from 57 live, recently trapped, adult and juvenile laggar falcons and from five dead birds were collected from Bahawalpur, Bahawalnagar, Mithi, Chachcro, Jacobabad and Karachi districts. Cadmium (Cd), lead (Pb) and mercury (Hg) were analysed by atomic absorption spectrophotometry (AAS), cobalt (Co), selenium (Se), zinc (Zn), scandium (Sc), chromium (Cr), cesium (Cs), lanthanum (La) and bromine (Br) by neutron activation analysis (NAA). Hg levels were below those found in other raptors with reduced reproductive success. No correlation was found between Hg and Se levels. For some metals and elements interpretation of results is difficult as no data exist in the literature. Concentrations did not differ significantly between males and females nor between juveniles and adults, but differed among districts for Pb, Hg, Co, Sc, Cr, La and Br. A significant correlation was found between Pb concentration and occurrence of louse eggs. As the laggar is resident or a partial local migrant, it is probable that the metal burden in adult and juvenile feathers reflects the level of contamination in these particular districts.     

Effect of maternal dietary hexachlorocyclohexane exposure on pup survival and growth in albino rats.

In adult albino rats, maternal dietary beta- and gamma-hexachlorocyclohexane (HCH) intake during gestation upto 400 ppm level did not affect the number of litters produced. But about 50 and 100% pup mortality was found in 200 and 400 ppm beta-HCH group within 5 days of birth. Maternal mortality was observed in 800 ppm beta-HCH group during third week of gestation. The effect of maternal dietary intake of HCH isomers at 50 and 250 ppm level during gestation and/or lactation on perinatal development was also studied. The body weights and sizes of the newborn litters of mother rats exposed to dietary HCH isomers did not differ from controls. Similarly, the growth and development of the litters of HCH exposed mother rats that survived 28 day lactation period were found to be comparable to controls as evidenced by the body weight and weight of vital organs. However, liver weight increases were found in the 28 days weaned litters wherever the mothers had been exposed to HCH isomers during lactation. Lowered kidney weight was seen in litters of mother rats fed 250 ppm gamma-HCH during gestation and lactation. The brain and testis weights were not affected in the litters of any experimental groups.     

低温降解六六六优势菌种的选育研究

通过实验,筛选出低温条件(≤10℃)下降解六六六的优势菌株--1号菌株,同时利用正交实验测得该菌株的最佳降解条件为:pH=5.5、接菌量2 g/L、NH4Cl 0.8 g/L、KH2PO4 0.6 g/L、MgSO4 0.2 g/L.在此条件下,经30 d驯化后的菌株对六六六的降解率由原来的54.71%提高到62.58%     

Distribution pathways of hexachlorocyclohexane isomers in a soil-plant-air system. A case study with Cynara scolymus L. and Erica sp. plants grown in a contaminated site

This study focuses on the main routes of distribution and accumulation of different hexachlorocyclohexane (HCH) isomers (mainly α-, β-, γ- and δ-HCH) in a soil-plant-air system. A field assay was carried out with two plant species, Cynara scolymus L. and Erica sp., which were planted either: (i) directly in the HCH-contaminated soil; or (ii) in pots filled with uncontaminated soil, which were placed in the HCH-contaminated soil. Both plant species accumulated HCH in their tissues, with relatively higher accumulation in above-ground biomass than in roots. The β-HCH isomer was the main isomer in all plant tissues. Adsorption of HCH by the roots from contaminated soil (soil → root pathway) and adsorption through the aerial biomass from either the surrounding air, following volatilization of the contaminant (soil → air → shoot pathway), and/or contact with air-suspended particles contaminated with HCH (soil particles → shoot pathway) were the main mechanisms of accumulation. These results may have important implications for the use of plants for reducing the transfer of contaminants via the atmosphere.     

Evaluation of hexachlorocyclohexane contamination from the last lindane production plant operating in India

Purpose

??-Hexachlorocyclohexane (HCH), ??-HCH, and lindane (??-HCH) were listed as persistent organic pollutants by the Stockholm Convention in 2009 and hence must be phased out and their wastes/stockpiles eliminated. At the last operating lindane manufacturing unit, we conducted a preliminary evaluation of HCH contamination levels in soil and water samples collected around the production area and the vicinity of a major dumpsite to inform the design of processes for an appropriate implementation of the Convention.

Methods

Soil and water samples on and around the production site and a major waste dumpsite were measured for HCH levels.

Results

All soil samples taken at the lindane production facility and dumpsite and in their vicinity were contaminated with an isomer pattern characteristic of HCH production waste. At the dumpsite surface samples contained up to 450?g?kg^?1 ?? HCH suggesting that the waste HCH isomers were simply dumped at this location. Ground water in the vicinity and river water was found to be contaminated with 0.2 to 0.4?mg?l^?1 of HCH waste isomers. The total quantity of deposited HCH wastes from the lindane production unit was estimated at between 36,000 and 54,000?t.

Conclusions

The contamination levels in ground and river water suggest significant run-off from the dumped HCH wastes and contamination of drinking water resources. The extent of dumping urgently needs to be assessed regarding the risks to human and ecosystem health. A plan for securing the waste isomers needs to be developed and implemented together with a plan for their final elimination. As part of the assessment, any polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF) generated during HCH recycling operations need to be monitored.     

Vehicle dependent bioavailability of polychlorinated dibenzo-p-dioxins (PCDDs) and -dibenzofurans (PCDFs) in the rat

PCDDs and PCDFs were administered as fly ash (500 mg) or fly ash extract to male Wistar rats. The extract was administered orally and intravenously by using arachidis oil and miglyol 812 as oily vehicles. Liver retentions were determined after 48 hours as a degree of bioavailability. In all experiments only the 2,3,7,8-substituted congeners, with the exception of 2,3,4,6,7-PnCDF, were detected in the liver. The dose was 10 to 40 ng for each congener. The lowest bioavailability was found in the experiments with crude or hydrochloric acid pretreated fly ash. Liver retentions were comparable for both experiments with fly ash (0.4 – 3.8%) and were approximately 10 times higher in the oral experiments with oily vehicles. Miglyol 812 produced slightly lower liver retentions compared with arachidis oil. Intravenous dosage with miglyol 812 resulted in liver retentions twice as high as oral administration with this vehicle.