Enhanced reductive dechlorination of 1,1,1-trichloroethane using zero-valent iron-biochar-carrageenan microspheres: preparation and microcosm study.

In this study, a composite remediation material for the enhanced reductive dechlorination (ERD) of 1,1,1-trichloroethane (1,1,1-TCA) in aqueous solution was prepared. This material was comprised of biochar as the carrier and adsorbent, and carrageenan (CG) as the embedding medium to entrap the organic carbon sources and zero-valent iron (ZVI). We determined the suitable biochar dosage and organic carbon source in the composite alongside the optimal preparation conditions. Furthermore, using an anaerobic microcosm study, we discussed the performance and possible mechanisms of the composite on 1,1,1-TCA removal in aqueous solution. From this, we found that the suitable dosage of biochar in water during the preparation of composite microspheres was 0.2% (w/v). Under this condition, the biochar had a strong capacity to adsorb 1,1,1-TCA with a removal efficiency of 84.2%. Soluble starch was selected as the appropriate organic carbon source, because starch-microspheres show an excellent slow-release effect in water. The optimal preparation conditions of microspheres were identified as follows: 2% CG (w/v) colloidal solution, 6% CaCl2 (w/v) solution, and a 12-h curing time. After 25-day incubation with the composite prepared under optimized conditions, the removal efficiency of 1,1,1-TCA was 95.68%, which was 24.69% higher than that observed in the microcosm with a commercial remediation material. The scanning electron microscopy (SEM) images show that the amounts of ZVI and soluble starch inside the microsphere decreased obviously, while the biochar amount remained about the same. This indicates that 1,1,1-TCA in aqueous solution was mainly removed via soluble starch-enhanced biotic reductive dechlorination and ZVI-enhanced abiotic reductive dechlorination. The changes in microbial community structure demonstrate that the composite stimulated the activities of functional anaerobic bacteria, in particular, regarding dechlorination and fermentation abilities in the microcosm, therefore enhancing the anaerobic biodegradation of 1,1,1-TCA. This study suggests that the composite, entrapping biochar, ZVI, and organic carbon source in CG microspheres can significantly enhance the reductive dechlorination of 1,1,1-TCA in aqueous solution. We anticipate this novel remediation material could be successfully applied to the in situ ERD remediation of natural groundwater mainly contaminated with 1,1,1-TCA.

Human Health Risk from Consumption of Marine Fish Contaminated with DDT and Its Metabolites in Maputo Bay, Mozambique.

Many countries with incidence of malaria, including those surrounding Maputo Bay, use dichloro-diphenyl-trichloroethane (DDT) to reduce mosquitoes. This study is the first to estimate the human health risk associated with consumption of marine fish from Maputo Bay contaminated with DDTs. The median for ∑DDTs was 3.8 ng/g ww (maximum 280.9 ng/g ww). The overall hazard ratio for samples was 1.5 at the 75th percentile concentration and 28.2 at the 95th percentile. These calculations show increased potential cancer risks due to contamination by DDTs, data which will help policy makers perform a risk-benefit analysis of DDT use in malaria control programs in the region.

Combination of zero-valent iron and anaerobic microorganisms immobilized in luffa sponge for degrading 1,1,1-trichloroethane and the relevant microbial community analysis.

1,1,1-Trichloroethane (1,1,1-TCA), a dense non-aqueous phase liquid (DNAPL), is relatively slow to remediate naturally; combination of zero-valent iron and immobilized microorganism is a potential means to accelerate DNAPL biodegradation. We first adopted high density luffa sponge (HDLS) as immobilized microorganism carrier. The experimental results demonstrated that (1) the supernatant liquid microorganisms were the optimal immobilized microorganisms for HDLS and (2) the combination of zero-valent iron and immobilized microorganisms accelerated 1,1,1-TCA transformation. Furthermore, in the long-term remediation process, anaerobic microorganisms produced reductant H2S which was beneficial to zero-valent iron PRBs. Through further study of the microbial community, we found that majority of the sulfate-reducing bacteria (SRB) perfectly adapted to the process of 1,1,1-TCA co-metabolism dechlorination. Desulfobulbus and Desulfococcus potentially were the special SRB that contributed significantly to TCA co-metabolism. Additionally, 1,1,1-TCA induced the generation of new SRB and stimulated the growth of majority of dominating methanogens. The results indicated that they played a constructive role in accelerating the dechlorination of 1,1,1-TCA, reduction of sulfate, and improving the production of CH4. Consequently, combination of zero-valent iron and immobilized microorganisms for remediating groundwater by contaminated 1,1,1-TCA is a sustainable and green remediation technology. Especially for groundwater of SO42- type contaminated by 1,1,1-TCA, in the long-term course of combination degradation, cyclic utilization of H2S to prolong the service life of zero-valent iron PRBs. H2 and CH4 generated to capture as potential energy resource. Based on this, a tentative reaction mechanism for Fe0 biodegradation of 1,1,1-TCA was proposed.

Particles and enzymes: Combining nanoscale zero valent iron and organochlorine respiring bacteria for the detoxification of chloroethane mixtures.

Nanoscale zero valent iron (nZVI) and organochlorine respiring bacteria (ORB) are two technologies used to detoxify chlorinated aliphatic hydrocarbons (CAHs). nZVI can rapidly detoxify high CAH concentrations, but is quickly oxidised and unable to degrade certain CAHs (e.g., 1,2-dichlorothane). In contrast, ORB can dechlorinate CAHs resistant to nZVI (e.g., 1,2-dichlorothane) but are inhibited by other CAHs of concern degradable by nZVI (e.g., chloroform and carbon tetrachloride). Combining the two was proposed as a unique treatment train to overcome each technology's shortcomings. In this study, this combined remedy was investigated using a mixture of 1,2-dichloroethane, degradable by ORB but not nZVI, and 1,1,2-trichloroethane, susceptible to both. Results indicated that nZVI rapidly dechlorinated 1,1,2-trichloroethane when supplied above 0.5 g/L, however ORB were inhibited and unable to dechlorinate 1,2-dichloroethane. pH increase and ionic species associated with nZVI did not significantly impact ORB, pinpointing Fe(0) particles as responsible for ORB inhibition. Below 0.05 g/L nZVI, ORB activity was stimulated. Results suggest that combining ORB and nZVI at appropriate doses can potentially treat a wider range of CAHs than each individual remedy. At field sites where nZVI was applied, it is likely that in situ nZVI concentrations were below the threshold of negative consequences.

Detoxification of 1,1,2-trichloroethane to ethene by desulfitobacterium and identification of its functional reductase gene.

1,1,2-trichloroethane (1,1,2-TCA) has become a common groundwater pollutant due to historically extensive utilization, improper disposal, as well as from incomplete dechlorination of 1,1,2,2-tetrachloroethane. Currently, limited information is available on microbial detoxification of 1,1,2-TCA. Desulfitobacterium sp. strain PR, which was isolated from an anaerobic bioreactor maintained to dechlorinate chloroethenes/ethanes, exhibited the capacity to dechlorinate 1,1,1-trichloroethane and chloroform. In this study, the dechlorinating ability of strain PR was further explored. Strain PR showed the capability to dechlorinate 1,1,2-TCA (~1.12 mM) predominantly to 1,2-dichloroethane (1,2-DCA) and chloroethane, and to trace amounts of vinyl chloride and ethene within 20 days. Strain PR coupled growth with dechlorination of 1,1,2-TCA to 1,2-DCA, while no cell growth was observed with dechlorination of 1,2-DCA to chloroethane. Later, through transcriptomic and enzymatic analysis, the reductive dehalogenase CtrA, which was previously reported to be responsible for 1,1,1-trichloroethane and chloroform dechlorination, was identified as the 1,1,2-TCA reductive dehalogenase. Since trichloroethene (TCE) is usually co-contaminated with 1,1,2-TCA, a co-culture containing Dehalococcoides mccartyi strain 11a capable of detoxifying TCE and 1,2-DCA and strain PR was established. Interestingly, this co-culture dechlorinated 1,1,2-TCA and TCE to the non-toxic end-product ethene within 48 days without chloroethane production. This novel pathway avoids production of the carcinogenic intermediate dechlorination product vinyl chloride, providing a more environmentally friendly strategy to treat 1,1,2-TCA.

Inflammatory and cardiometabolic risk on obesity: role of environmental xenoestrogens.

CONTEXT: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. OBJECTIVE: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND PARTICIPANTS: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m(2)) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. RESULTS: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. CONCLUSIONS: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women.

Bio-beads with immobilized anaerobic bacteria, zero-valent iron, and active carbon for the removal of trichloroethane from groundwater.

Chlorinated hydrocarbons are the most common organic pollutants in groundwater systems worldwide. In this study, we developed bio-beads with immobilized anaerobic bacteria, zero-valent iron (ZVI), and activated carbon (AC) powder and evaluated their efficacy in removing 1,1,1-trichloroethane (TCA) from groundwater. Bio-beads were produced by polyvinyl alcohol, alginate, and AC powder. We found that the concentration of AC powder used significantly affected the mechanical properties of immobilized bio-beads and that 1.0 % (w/v) was the optimal concentration. The bio-beads effectively degraded TCA (160 mg L(-1)) in the anaerobic medium and could be reused up to six times. The TCA degradation rate of bio-beads was 1.5 and 2.3 times greater, respectively, than ZVI + AC treatment or microbes + AC treatment. Measuring FeS produced by microbial reactions indicated that TCA removal occurred via FeS-catalyzed dechlorination. Analysis of clonal libraries derived from bio-beads demonstrated that the dominant species in the community were Betaproteobacteria and Gammaproteobacteria, which may contribute to the long-term stability of ZVI reactivity during TCA dechlorination. This study shows that the combined use of immobilized anaerobic bacteria, ZVI, and AC in bio-beads is effective and practical for TCA dechlorination and suggests they may be applicable towards developing a groundwater treatment system for the removal of TCA.

The impact of chlorinated solvent co-contaminants on the biodegradation kinetics of 1,4-dioxane.

1,4-Dioxane (dioxane), a probable human carcinogen, is used as a solvent stabilizer for 1,1,1-trichloroethane (TCA) and other chlorinated solvents. Consequently, TCA and its abiotic breakdown product 1,1-dichloroethene (DCE) are common co-contaminants of dioxane in groundwater. The aerobic degradation of dioxane by microorganisms has been demonstrated in laboratory studies, but the potential effects of environmentally relevant chlorinated solvent co-contaminants on dioxane biodegradation have not yet been investigated. This work evaluated the effects of TCA and DCE on the transformation of dioxane by dioxane-metabolizing strain Pseudonocardia dioxanivorans CB1190, dioxane co-metabolizing strain Pseudonomas mendocina KR1, as well as Escherichia coli expressing the toluene monooxygenase of strain KR1. In all experiments, both TCA and DCE inhibited the degradation of dioxane at the tested concentrations. The inhibition was not competitive and was reversible for strain CB1190, which did not transform the chlorinated solvents. For both strain KR1 and toluene monooxygenase-expressing E. coli, inhibition of dioxane degradation by chlorinated solvents was competitive and irreversible, and the chlorinated solvents were degraded concurrently with dioxane. These data suggest that the strategies for biostimulation or bioaugmentation of dioxane will need to consider the presence of chlorinated solvents during site remediation.

Bioaccumulation of heavy metals and two organochlorine pesticides (DDT and BHC) in crops irrigated with secondary treated waste water.

Four crop plants Oryza sativa (rice), Solanum melongena (brinjal), Spinacea oleracea (spinach) and Raphanus sativus (radish) were grown to study the impact of secondary treated municipal waste water irrigation. These plants were grown in three plots each of 0.5 ha, and irrigated with secondary treated waste water from a sewage treatment plant. Sludge from the same sewage treatment plant was applied as manure. Cultivated plants were analyzed for accumulation of heavy metals and pesticides. Results revealed the accumulation of six heavy metals cadmium (Cd), chromium (Cr), iron (Fe), copper (Cu), nickel (Ni), and zinc (Zn) as well as two pesticides [1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane; DDT] and benzene hexa chloride (BHC). Order of the plants for the extent of bioaccumulation was S. oleracea > R. sativus > S. melongena > O. sativa. The study has shown the secondary treated waste water can be a source of contamination to the soil and plants.

Concurrent bioremediation of perchlorate and 1,1,1-trichloroethane in an emulsified oil barrier.

A detailed field pilot test was conducted to evaluate the use of edible oil emulsions for enhanced in situ biodegradation of perchlorate and chlorinated solvents in groundwater. Edible oil substrate (EOS) was injected into a line of ten direct push injection wells over a 2-day period to form a 15-m-long biologically active permeable reactive barrier (bio-barrier). Field monitoring results over a 2.5-year period indicate the oil injection generated strongly reducing conditions in the oil-treated zone with depletion of dissolved oxygen, nitrate, and sulfate, and increases in dissolved iron, manganese and methane. Perchlorate was degraded from 3100 to 20,000 microg/L to below detection (<4 microg/L) in the injection and nearby monitor wells within 5 days following the injection. Two years after the single emulsion injection, perchlorate was less than 6 microg/L in every downgradient well compared to an average upgradient concentration of 13,100 microg/L. Immediately after emulsion injection, there were large shifts in concentrations of chlorinated solvents and degradation products due to injection of clean water, sorption to the oil and adaptation of the in situ microbial community. Approximately 4 months after emulsion injection, concentrations of 1,1,1-trichloroethane (TCA), perchloroethene (PCE), trichloroethene (TCE) and their degradation products appeared to reach a quasi steady-state condition. During the period from 4 to 18 months, TCA was reduced from 30-70 microM to 0.2-4 microM during passage through the bio-barrier. However, 1-9 microM 1,1-dichloroethane (DCA) and 8-14 microM of chloroethane (CA) remained indicating significant amounts of incompletely degraded TCA were discharging from the oil-treated zone. During this same period, PCE and TCE were reduced with concurrent production of 1,2-cis-dichloroethene (cis-DCE). However, very little VC or ethene was produced indicating reductive dechlorination slowed or stopped at cis-DCE. The incomplete removal of TCA, PCE and TCE is likely associated with the short (5-20 days) hydraulic retention time of contaminants in the oil-treated zone. The permeability of the injection wells declined by 39-91% (average=68%) presumably due to biomass growth and/or gas production. However, non-reactive tracer tests and detailed monitoring of the perchlorate plume demonstrated that the permeability loss did not result in excessive flow bypassing around the bio-barrier. Contaminant transport and degradation within the bio-barrier was simulated using an advection-dispersion-reaction model where biodegradation rate was assumed to be linearly proportional to the residual oil concentration (Soil) and the contaminant concentration. Using this approach, the calibrated model was able to closely match the observed contaminant distribution. The calibrated model was then used to design a full-scale barrier to treat both ClO4 and chlorinated solvents.

Propionicicella superfundia gen. nov., sp. nov., a chlorosolvent-tolerant propionate-forming, facultative anaerobic bacterium isolated from contaminated groundwater.

A novel strain, designated as BL-10(T), was characterized using a polyphasic approach after isolation from groundwater contaminated by a mixture of chlorosolvents that included 1,1,2-trichloroethane, 1,2-dichloroethane, and vinyl chloride. Stain BL-10(T) is a facultatively anaerobic bacterium able to ferment glucose to form propionate, acetate, formate, lactate, and succinate. Fermentation occurred in the presence of 1,2-dichloroethane and 1,1,2-trichloroethane at concentrations to at least 9.8 and 5.9 mM, respectively. Cells are Gram-positive, rod-shaped, non-motile, and do not form spores. Oxidase and catalase are not produced and nitrate reduction did not occur in PYG medium. Menaquinone MK-9 is the predominant respiratory quinone and meso-diaminopimelic acid is present in the cell wall peptidoglycan layer. Major cellular fatty acids are C(15:0), iso C(16:0), and anteiso C(15:0). Genomic DNA G + C content is 69.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed strain BL-10(T) to fall within the radiation of genera Propionicimonas and Micropruina. On the basis of the results obtained in this study, it is proposed that strain BL-10(T) should be classified as a novel taxon, for which the name Propionicicella superfundia gen. nov., sp. nov. is proposed. The type strain of Propionicicella superfundia is BL-10(T) (=ATCC BAA-1218(T), =LMG 23096(T)).

Batch-test study on the dechlorination of 1,1,1-trichloroethane in contaminated aquifer material by zero-valent iron.

Chlorinated aliphatic hydrocarbons are common groundwater contaminants. One possible remediation option is in-situ reductive dechlorination by zero-valent iron, either by direct injection or as reactive barriers. Chlorinated ethenes (tetrachloroethene: PCE; trichloroethene: TCE) have received extensive attention in this context. However, another common groundwater pollutant, 1,1,1-trichlorethane (TCA), has attracted much less attention. We studied TCA reduction by three types of granular zero-valent irons in a series of batch experiments using polluted groundwater, with and without added aquifer material. Two types of iron were able to reduce TCA completely with no daughter product concentration increases (1,1-dichloroethane: DCA; chloroethane: CA). One type of iron showed slower reduction, with intermediate rise of DCA and CA concentrations. When evaluating the formation of daughter products, the tests on the groundwater alone showed different results than the groundwater plus aquifer batches: DCA did not temporarily accumulate in the batches with added aquifer material, contrary to the batches without added aquifer material. 1,1-dichloroethene (DCE, also present in the groundwater as an abiotic degradation product of TCA) was also reduced slower in the batches without added aquifer material than in the batches with aquifer material. Redox potentials gradually decreased to low values in batches with aquifer material without iron, while the batches with groundwater alone maintained a constant higher redox potential. Either adsorption processes or microbiological activity in the samples could explain these phenomena. Polymerase Chain Reaction (PCR: a targeted gene probe technique) for chlorinated aliphatic compound (CAH)-degrading bacteria confirmed the presence of Dehalococcoides sp. (chloroethene-degraders) but was negative for Desulfobacterium autotrophicum (a known co-metabolic TCA degrader). DCA reduction was rate determining: first-order half-lives of 300-350 h were observed. TCA was fully removed within hours. CA is resistant to reduction by zero-valent iron but it is known to hydrolyze easily. Since CA did not accumulate in our batches, it may have disappeared by the latter mechanism or it may not have formed as a major daughter product.

Environmental and biological monitoring of occupational exposure to 1,1,1-trichloroethane.

Fifty workers involved in various degreasing and cleaning processes using 1,1,1-trichloroethane (1,1,1-TCE) were studied with respect to personal and static exposures. In addition, end-of-shift expired air and venous blood samples were taken for analysis of the parent compound. Urinary samples were also obtained at the same time for analysis of its metabolites-trichloroethanol (TCOH) and trichloracetic acid (TCA). The results show that open/manual degreasing processes generate the highest environmental solvent levels (mean = 819.9 mg/m3; SD = 781.9 mg/m3) followed by jet-spray cleaning (mean = 460.5 mg/m3; SD = 292.4 mg/m3), vapour degreasing (mean = 365.3 mg/m3; SD = 279.9 mg/m3) and ultrasonic degreasing (mean = 134.7 mg/m3; SD = 121.0 mg/m3). Personal exposure levels were well correlated with concentrations of 1,1,1-TCE in end-of-shift expired air (r = 0.81) and venous blood samples (r = 0.88) but only moderately correlated with concentrations of its metabolites in urine (r = 0.49 for TCOH; r = 0.58 for TCA). Static (area) samples were poorly correlated with the biological exposure indices studied.

Estimating skin permeation. The validation of five mathematical skin permeation models.

This study provides an analysis of the reliability of five mathematical models, simulating permeation of substances through the skin from aqueous solutions. An extensive database was generated, containing data on 123 measured permeation coefficients of 99 different chemicals and their physicochemical properties. In addition, in this database all relevant experimental conditions are included. The coefficients of the different skin permeation models were estimated by non-linear multiple regression, using the octanol-water partition coefficient and the molecular weight as independent parameters. The reliability of the models was evaluated by testing variation of regression coefficients and of residual variance for subsets of data, randomly selected from the complete database. Three models were considered to provide reliable estimations of the skin permeation coefficient. These are based on the McKone and Howd model, the Guy and Potts model and the Robinson model. The last-mentioned two models were adaptations, because MW0.5 as independent parameter provided a better fit than MW (MW = molecular weight) in the original models. The McKone and Howd model and the Robinson model have the advantage, that they predict more precisely the skin permeation of highly hydrophilic and highly lipophilic chemicals compared to the Guy and Potts model. The revised Robinson model resulted always in the smallest residual variance.

Urinary methylchloroform rather than urinary metabolites as an indicator of occupational exposure to methylchloroform.

In order to compare methylchloroform (MC, or 1,1,1-trichloroethane) per se and its metabolites in urine as indicators of occupational exposure to this solvent, 50 male solvent workers were studied in the second half of a working week to evaluate the exposure-excretion relationship. The time-weighted average intensity of solvent exposure of individuals during an 8-h shift was monitored by personal diffusive sampling. Urine samples were collected near the end of the shift and were analyzed for MC and its metabolites [i.e., trichloroacetic acid (TCA), trichloroethanol (TCE) and total trichloro-compounds (TTC; the sum of TCA and TCE)] by head-space gas chromatography. MC per se, TCA, TCE, and TTC in urine correlated significantly (P < 0.01) with MC in ambient air, and among the four the correlation coefficient was highest for MC. The same result were obtained by multiple regression analysis in which ambient air MC was taken as the dependent variable and either the three indicators urinary MC, TCA, and TCE or the two indicators urinary MC and TTC were taken as independent variables. Taking the specificity and selectivity of the analyte as well as the simple and hazardous chemical-free procedure of analysis into consideration, it is concluded that MC is the analyte of choice as an indicator of occupational exposure to MC, when urine is selected as a specimen available by noninvasive sampling.

Demethylation pathways in caffeine metabolism as indicators of variability in 1,1,1-trichloroethane oxidation in man.

Twenty volunteers were exposed to 191 +/- 7 p.p.m. 1,1,1-trichloroethane or 50 +/- 2 p.p.m. perchloroethylene vapour for 6 hr. They were then evaluated for their rate of caffeine metabolism, mephenytoin hydroxylation and debrisoquine hydroxylation. Seven subjects were identified as 'fast acetylators' of caffeine and one person as a slow metabolizer of debrisoquine. The "slow acetylators" exposed to perchloroethylene excreted an average of 3.83 +/- 0.35 mg trichloroacetic acid within 24 hr (N = 13, +/- S.E.) and the 'fast acetylators' 3.58 +/- 0.48 mg (N = 7, +/- S.E.). The excretion of trichloroethanol by the same persons after 1,1,1-trichloroethane exposure was 14.1 +/- 1.12 mg and 16.7 +/- 1.48 mg, respectively. The excretion of trichloroacetic acid in the latter exposure varied significantly between the seven 'fast' and 13 'slow acetylators' (0.43 +/- 0.08 mg versus 1.03 +/- 0.19 mg; +/- S.E.; P = 0.037). A multiple linear regression analysis confirmed this association when other factors, such as body weight, creatinine clearance, smoking habit and alcohol consumption, were taken into account. One volunteer proved to be a poor hydroxylator of debrisoquine and excreted half the amount of trichloroacetic acid in the perchloroethylene exposure and half the amount of trichloroethanol in the 1,1,1-trichloroethane exposure compared to the others. A reduction in the solvent metabolism could thus be predicted by the debrisoquine test. On the other hand, the caffeine test predicted faster oxidation of trichloroethanol which could be of toxicological and pharmacological importance e.g. in the clinical use of chloral.

Investigations on metabolism and carcinogenicity of 1,1,2-trichloroethane.

Two groups of male and female Sprague-Dawley rats (50 animals/group per sex) were treated with either 15.37 or 46.77 mumole of 1,1,2-TCE in DMSO/rat for 2 years. The animals were treated once a week by s.c. injection of test compound in the skin of neck. Two groups of controls received either DMSO or no treatment at all. The incidence of benign mesenchymal and epithelial tumors was not significant when compared with either DMSO-treated or untreated controls. The animals treated with 46.77 mumole 1,1,2-TCE significantly developed sarcomas when compared with the untreated controls. In a further experiment, either 40 mumole or 160 mumole 1,1,2-TCE was injected into male Wistar rats and the metabolites, TdGA and HEMA, were determined in 24-h urine samples. Comparative studies were carried out giving equimolar amounts of chloroethanol and 2-chloroacetaldehyde diethyl acetal. Analysis of the metabolites showed that no detectable HEMA was excreted in urine after treatment of rats with 1,1,2-TCE or chloroethanol. TdGA was excreted in urine much more among chloroacetaldehyde-treated animals than among 1,1,2-TCE- or chloroethanol-treated rats.

Pharmacokinetic factors and their implication in the induction of mouse liver tumors by halogenated hydrocarbons.

The presently available data on pharmacokinetics of halogenated solvents which produce hepatic tumors in B6C3F1 mice, but not in rats, are reviewed. Such compounds are trichloroethylene, perchloroethylene, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, and dichloromethane. It seems likely that higher metabolic rates in mice (compared with other species) may lead to a species-selective toxicity of such compounds. Recurrent cytotoxicity which leads to stimulation of cell replication seems to be a contributing factor in the pathogenesis of mouse liver tumors. However, it is likely that more than one factor contributes to the unique tumor response of the B6C3F1 mouse.

A physiologically based simulation approach for determining metabolic constants from gas uptake data.

In vivo metabolic constants were determined in male Fischer rats for five chemicals: 1,1-dichloroethylene (1,1-DCE), diethyl ether (DE), bromochloromethane (BCM), methyl chloroform (MC), and carbon tetrachloride (CCl4). A closed recirculated exposure system was used to collect a series of uptake curves for each chemical at a range of initial concentrations. The shapes of these curves were a function of the tissue partition coefficients and the kinetic characteristics of the metabolism of these chemicals. Tissue:air partition coefficients were experimentally determined for each chemical and incorporated into a physiological kinetic model which was then used to simulate the uptake process. An optimal fit of the family of uptake curves for each chemical was obtained by adjusting the biochemical constants for metabolism of the chemical. Metabolism of both 1,1-DCE and CCl4 was represented by a single saturable process while MC required only a first-order pathway. BCM and DE exhibited a combination of both a saturable and a first-order process. Pyrazole, which blocks oxidative microsomal metabolism, inhibited the saturable pathways of 1,1-DCE, BCM, DE, and CCl4 metabolism and abolished the first-order pathway for MC. The maximum velocity of metabolism for the saturable pathway with 1,1-DCE, BCM, DE, and CCl4 for a 225-g rat was 27.2, 19.9, 26.1, and 0.92 mol/hr, respectively. The simulation approach for analyzing gas uptake data distinguishes between single and multiple metabolic pathways and provides kinetic constants that can be used in predictive toxicokinetic models for describing constant concentration inhalation exposure as well as exposures by other routes of administration.