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[Immunohistochemical study of mast cells in allergic rhinitis: an indicator for assessing the therapeutic effect of chemosurgery using trichloroacetic acid].

An immunohistochemical study was conducted on the degree of tryptase-positive, chymase-negative mast cells (MCT) and tryptase-positive, chymase-positive mast cells (MCTC) infiltration in the inferior turbinates of 15 patients with perennial allergic rhinitis who underwent septal reconstruction and bilateral inferior turbinectomy 85 +/- 21 days after unilateral chemosurgical treatment using trichloroacetic acid (TCA). In samples without TCA treatment, many MCTs were observed in the mucosal epithelium near the basement membrane, especially in the area where many goblet cells were found, and some MCTs were found around the glands and vessels in the subepithelial layer. Most MCTCs were found in the subepithelial layer, and some in the epithelial layer. On the TCA-treated side, part of the epithelium disappeared, becoming squamatized epithelium in which MCTs were scarcely observed. Statistically, the number of mast cell on the side of TCA treatment was significantly less than on the non-treated side in the epithelial layer. In treated subepithelium layer, both MCTs and MCTCs were significantly fewer than on the non-treated side. These pathological findings suggest that TCA surgery has clinical potential to improve allergic rhinitis symptoms.

Adult↗

Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid.

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the lactating rat and nursing pup. The lactating dam was exposed to TCE either by inhalation or by ingestion in drinking water. The nursing pup's exposure to TCE was by ingestion of maternal milk containing TCE. The kinetics of trichloroacetic acid (TCA), a metabolite of TCE, were described in the lactating dam and developing pup by a hybrid one-compartment model. The lactating dam's exposure to TCA was from metabolism of TCE to TCA. The pup's exposure to TCA was from metabolism of TCE ingested in suckled milk and from direct ingestion of TCA in maternal milk. For the PB-PK model, partition coefficients (PCs) were determined by vial equilibration, and metabolic constants for TCE oxidation, by gas uptake methods. The blood/air and the fat/blood PCs for the dam were 13.1 and 34.2, and for the pup, 10.6 and 42.3, respectively. The milk/blood PC for the dam was 7.1. In lactating rats and rat pups (19-21 days old) the maximum velocities of oxidative metabolism were 9.26 +/- 0.073 and 12.94 +/- 0.107 mg/kg/hr. The plasma elimination rate constant (K = 0.063 +/- 0.004 hr-1) and apparent volume of distribution (Vd = 0.568 liter/kg) for TCA in the lactating dam were estimated from both intravenous dosing studies and an inhalation study with TCE. For the pup, K (0.014 +/- hr-1) and Vd (0.511 liter/kg) were estimated from a single 4-hr inhalation exposure with TCE. The dose-rate-dependent stoichiometric yield of TCA from oxidative metabolism of TCE in the lactating rat is 0.17 for a low-concentration inhalation exposure (27 ppm TCE) and 0.27 for an exposure above metabolic saturation (about 600 ppm TCE). For the pup, the stoichiometric yield of TCA is 0.12. With changing physiological values during lactation for compartmental volumes, blood flows, and milk yields obtained from the published literature and kinetic parameters and PCs determined by experimentation, a PB-PK model was constructed to predict maternal and pup concentrations of TCE and TCA. To test the fidelity of the PB-PK lactation model, a multiday inhalation exposure study was conducted from Days 3 to 14 of lactation and a drinking water study, from Days 3 to 21 of lactation. The inhalation exposure was 4 hr/day, 5 days/week, at 610 ppm. The TCE concentration in the drinking water was 333 micrograms/ml. Prediction compared favorably with limited data obtained at restricted time points during the period of lactation.

Animals↗

[Reductive dechlorination of trichloroacetic acid by bioelectrochemically catalytic method].

Direct electrochemical behaviors of hemoglobin (Hb) immobilized on carbon nanotube (CNT) modified carbon paste electrode with adsorption were investigated. Cyclic voltammetry of Hb-CNT-modified electrode showed a pair of well-defined and nearly reversible peaks for HbhemeFe(III) /Fe(II) redox couple in pH = 7 PBS buffers. The electrocatalytic behaviors of Hb-CNT-modified electrode for the reductive dechlorination of trichloroacetic acid (TCA) were studied by cyclic voltammmetry and fixed-potential electrolysis technique, and the reductive mechanism of TCA was discussed by analysis of reduction products. The results showed that Hb-CNT-modified electrode possessed good electro-catalytic activity for reduction of TCA and the dechlorination of TCA was stepwise, following the pathway of trichloroacetic--> dichloroacetic--> monochloroacetic--> acetic. The dechlorination of TCA in waster water was investigated using a two-compartment flow reactor with working electrode compartment packed with Hb-CNT-modified graphite electrode. The conversion of TCA was 40.13% with electrolysis for 180 min at - 0.60V (vs. SCE).

Adsorption↗

Biotransformation of perchloroethene: dose-dependent excretion of trichloroacetic acid, dichloroacetic acid, and N-acetyl-S-(trichlorovinyl)-L-cysteine in rats and humans after inhalation.

Chronic exposure of rodents to perchloroethene (PER) increased the incidence of liver tumors in male mice and resulted in a small but significant increase in the incidence of renal tumors in male rats. The tumorigenicity of PER is mediated by metabolic activation reactions. PER is metabolized by cytochrome P450 and by conjugation with glutathione. Cytochrome P450 oxidation of PER results in trichloroacetyl chloride which reacts with water to trichloroacetic acid (TCA) which is excreted. The formation of S-(trichlorovinyl)glutathione (TCVG) from PER results in nephrotoxic metabolites. TCVG is cleaved to S-(trichlorovinyl)-L-cysteine (TCVC) and acetylated to N-acetyl-S-(trichlorovinyl)-L-cysteine (N-ac-TCVC), which is excreted with urine. TCVC is also cleaved in the kidney by cysteine conjugate beta-lyase to dichlorothioketene which may react with water to dichloroacetic acid (DCA) or with cellular macromolecules. The object of this study was to comparatively quantify the dose-dependent excretion of PER metabolites in urine of humans and rats after inhalation exposure. Three female and three male human volunteers and three female and three male rats were exposed to 10, 20, and 40 ppm PER for 6 h, and three female and three male rats to 400 ppm. A dose-dependent increase in the excretion of TCA and N-ac-TCVC after exposure to PER was found both in humans and in rats. A total of 20.4 +/- 7.77 mumol of TCA and 0.21 +/- 0.05 mumol of N-ac-TCVC were excreted in urine of human over 78 h after the start of exposure to 40 ppm PER; only traces of DCA were present. After identical exposure conditions, rats excreted 1.64 +/- 0.42 mumol of TCA, 0.006 +/- 0.002 mumol of N-ac-TCVC and 0.18 +/- 0.04 mumol of DCA. Excretion of N-ac-TCVC in male rats exposed to 400 ppm PER (103.7 nmol) was significantly higher, compared to female rats (31.5 nmol) exposed under identical conditions. N-ac-TCVC was rapidly eliminated with urine both in humans (t1/2 = 14.1 h) and in rats (t1/2 = 7.5 h). When comparing the urinary excretion of N-ac-TCVC, a potential marker for the formation of reactive intermediates in the kidney, humans received a significantly lower dose (3 nmol/kg at 40 ppm) compared to rats (23.0 nmol/kg) after identical exposure conditions. In addition, rats excreted large amounts of DCA which likely is a product of the beta-lyase-dependent metabolism of TCVC in the kidney. The obtained data suggest that glutathione conjugate formation and beta-lyase-dependent bioactivation of TCVC in PER metabolism is significantly higher in rats than in humans. Thus, using rat tumorigenicity data for human risk assessment of PER exposure may overestimate human tumor risks.

Acetylcysteine↗

Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans.

The development and application of appropriate physiologically based pharmacokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolites have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloroacetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretion from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to estimate dose metrics resulting from TCE exposures and is therefore useful when considering the estimation of human health risks associated with such exposures.

Carcinogens↗

Histometric and histochemical analysis of the effect of trichloroacetic acid concentration in the chemical reconstruction of skin scars method.

BACKGROUND: Atrophic scars can be induced by various causes, including severely inflamed acne, chicken pox, and trauma. Many treatment modalities are used for reconstructing and improving the appearance of scars with various treatment results. OBJECTIVE: A recent report shows the clinical efficacy of the chemical reconstruction of skin scars (CROSS) method, which consists of the focal application of trichloroacetic acid (TCA) in a higher concentration. Histometric analysis of the CROSS method, however, has not yet been established. METHODS: In this study, five hairless mice were used to evaluate the effect of the CROSS method and to analyze the difference between the CROSS method and simple TCA application. RESULTS: Similar histologic changes were observed in the two methods, including epidermal and dermal rejuvenation with new collagen deposition. These changes, however, were more prominent in the CROSS method-treated areas, particularly when 100% TCA was used. CONCLUSION: The results of this study suggest that treatment of atrophic scars using the CROSS method is more effective than simple application of TCA in activating fibroblasts in the dermis and increasing the amount of collagen.

Administration, Topical↗

Sequential solubilization of proteins precipitated with trichloroacetic acid in acetone from cultured Catharanthus roseus cells yields 52% more spots after two-dimensional electrophoresis.

Sample preparation is still the most critical step in two-dimensional gel electrophoresis (2-DE), and needs to be optimized for each type of sample. To analyze the proteome of the medicinal plant Catharanthus roseus, we developed and evaluated a sequential solubilization procedure for the solubilization of proteins after precipitation in trichloroacetic acid and acetone. The procedure includes solubilization with a conventional urea buffer followed by a stronger solubilizing buffer containing thiourea. The sequential solubilization of the precipitated proteins results in very different spot patterns following 2-DE. The number of protein spots which could be detected in both samples of the sequential solubilization was only about 10% of the total number of spots. Compared to solubilization in a single step, the total number of spots that could be detected in the sequential solubilization procedure was increased by 52%. The method described is simple and is applicable to different types of plant tissue.

Acetone↗

Genital condylomas in pregnancy: use of trichloroacetic acid and laser therapy.

Genital condylomas in pregnancy pose several management problems for the obstetrician, including the mechanical problems of large condylomas and the issues relating to transmission of the human papillomavirus to the fetus during delivery. Transmission of papillomavirus occurs infrequently, but respiratory papillomatosis can result in mortality or lifelong morbidity. We evaluate our experience in treating condylomas in 32 pregnant women, using carbon dioxide laser therapy and 85% trichloroacetic acid. Condylomas in 31 (97%) of 32 women were controlled with this combination therapy. The only maternal complication was an episode of acute pyelonephritis secondary to urethral catheterization. One patient had premature rupture of the membranes 4 days after laser therapy and subsequently was delivered of a healthy neonate at 36 4/7 weeks. Prenatal photovaporization of condylomas appears to offer a method of treatment with a low complication and recurrence rate and helps avert the dilemma of whether patients with extensive genital condylomas should be delivered by cesarean section.

Adolescent↗

Effect of trichloroacetic acid on the isolation of tropomyosin from sea urchin lantern muscle.

Sea urchin lantern muscle tropomyosin showed two components in sodium dodecyl sulfate (SDS) gel electrophoresis in the presence of 5 M urea, although the molecular weights of these components were apparently identical. One of these components seemed to have been digested with an enzyme such as carboxypeptidase, and the tropomyosin had lost the abilities to polymerize and to bind to actin. A crude extract prepared from the lantern muscle treated with trichloroacetic acid (TCA) contained predominantly tropomyosin. Tropomyosin purified from TCA-treated lantern muscle seemed to be intact and retained the ability to bind to actin.

Animals↗

The phytotoxic effect of C(1)/C(2)-halocarbons and trichloroacetic acid on the steppe plant Artemisia lerchiana.

Artemisia lerchiana is a wormwood species of the Central Asian steppe regions, where it completely cover whole areas. For the first time it was possible to show through field experiments that C(1)/C(2) halocarbons (VCHCs), such as chloroform (CHL), tetrachloroethene (PER) and hexachloroethane (HEX), can be taken up by test plants of the species A. lerchiana via the soil/root pathway and metabolised inter alia into trichloroacetic acid (TCA) under semi-aride conditions. At the same time, chlorophyll a fluorescence measurements carried out on the test plants revealed a phytotoxic influence on plant vitality (max. decline in vitality of 52% with application of CHL) and less efficient energy flows in the photosynthesis mechanism of the A. lerchiana test plants. The authors examine possible links between the simultaneous appearance of VCHCs and additional drought stress in the acceleration of desertification processes.

Artemisia↗

Treatment of photodamaged skin with trichloroacetic acid and topical tretinoin.

BACKGROUND: Photodamaged skin typically displays lentigines, actinic keratoses, wrinkles, and textural alteration. Chemical peeling has been used to treat these, but few controlled studies have been performed to determine its efficacy. OBJECTIVE: Our purpose was to compare the efficacy of a medium-depth chemical peel with and without tretinoin before and after treatment. METHODS: Sixteen men with actinic damage including actinic keratoses were treated with a 40% trichloroacetic acid(TCA) chemical peel. Half were pretreated for 6 weeks with topical tretinoin; they also used tretinoin after the peel. Photographs were obtained at baseline and at 6 weeks and 6 months after treatment. Changes in specific features were rated by a panel of three examiners. RESULTS: Some improvement was noted in all patients. More rapid and even frosting was observed in the patients pretreated with tretinoin. Solar lentigines, actinic keratoses, and skin texture were the features of photoaging most affected; wrinkles were least affected. No statistically significant difference was found between patients treated with TCA and tretinoin (before and after peel) and those with TCA alone. CONCLUSION: A medium-depth chemical peel with 40% TCA alone produced moderate improvement in some manifestations of actinic damage but had little effect on wrinkles. Treatment with tretinoin before and after TCA did not significantly enhance the efficacy of the peel.

Administration, Cutaneous↗

31P NMR study of the desulfurization of oligonucleoside phosphorothioates effected by "aged" trichloroacetic acid solutions.

When employing phosphoramidites 1a-d in the solid-phase synthesis of oligonucleoside phosphorothioates, the thermolytic 2-[N-methyl-N-(2-pyridyl)]aminoethyl thiophosphate protecting group is lost to a large extent during the course of the synthesis. The resulting phosphorothioate diesters are then substantially desulfurized upon recurring exposure to a commercial solution of deblocking reagent during chain assembly. This problem is caused by the secondary decomposition product(s) of the reagent and is alleviated by using a fresh solution of the deblocking reagent prepared from solid trichloroacetic acid.

Base Sequence↗

A new treatment for syringoma. Combination of carbon dioxide laser and trichloroacetic acid.

BACKGROUND: Although syringoma represents a benign tumor of skin appendage, multiple and diffuse facial lesions can cause cosmetic problems for the affected individuals. Scarring, recurrence and postinflammatory hyperpigmentation can be serious troubles, especially for oriental people receiving various therapeutic modalities. OBJECTIVE: The purpose of this study was to evaluate the histopathologic and clinical efficacy of a new therapeutic approach for syringoma, consisting of combination of carbon dioxide (CO2) laser and 50% trichloroacetic acid (TCA). METHODS: Eighty skin biopsy specimens (45 patients) were evaluated to determine the depth of syringoma lesion. Among these, 28 specimens were obtained after a single test-pulse of CO2 laser (focused, superpulsed mode, power setting of 0.7-2 watts, beam diameter of 0.1 mm, pulse duration of 0.1 seconds), and 3 specimens after one pass of CO2 laser and 50% TCA. The depths of laser-induced vaporization and TCA-induced tissue necrosis were measured. Twenty patients were treated with the combination therapy of CO2 laser (two passes of laser) and 50% TCA. Clinical effectiveness and complications of combination therapy were evaluated by direct observation and photographs. RESULTS: Tumor depth: Analysis of eight specimens revealed tumor depth of 0.70 +/- 0.20 mm (mean +/- SD), ranging from 0.4-1.2 mm. There were no correlations between tumor depth and age of onset or duration of the tumor. Laser penetration depth: CO2 laser irradiation, 0.7-2 watts, induced vaporization of 0.29 +/- 0.12 mm in depth with carbonized rim of 0.1 +/- 0.03 mm width (n = 28 from 15 patients). With laser power of 1 watt, vaporization ranged from 0.17-0.45 mm in depth. Laser and TCA induced necrosis: TCA application resulted in extra tissue necrosis of 0.22-0.25 mm in depth beyond the level achieved by laser vaporization. CLINICAL FINDINGS: Among the 20 patients treated with the combination therapy, therapeutic effect for 11 patients was excellent, 6 patients showed good clinical response, and 3 patients were fair. There were no serious complications resulting from this procedure such as infection, scarring or textural change. CONCLUSION: The application of 50% TCA after CO2 laser irradiation was effective for removing deep-seated syringoma cells and for reducing the side effects, especially scarring. To the best of our knowledge, this is the first study introducing the combination of CO2 laser and TCA for removal of syringoma.

Adolescent↗

Treatment of multiple apocrine hidrocystomas with trichloroacetic acid.

The apocrine hidrocystoma is a benign adenomatous cystic proliferation derived from apocrine glands, which frequently occurs in periocular tissues. These cystadenomas may occur bilaterally, in multiple disfiguring confluent groups on both the upper and lower lids. Although these lesions have been treated successfully with meticulous surgical extirpation and electrosurgery, this report describes the successful treatment of two patients, each with multiple large (>7 mm) periocular apocrine hidrocystomas by either chemical ablation of the cystic epithelium with trichloroacetic acid (TCA) or surgical excision. Examination of the cysts at 1, 3, and 6 months after TCA treatment revealed well-healed lesions without cyst recurrence. Most of the TCA-treated cysts resolved completely, without leaving any trace to clinical examination. Treatment of cysts with TCA was technically simpler and much less time-consuming than surgical excision. The treatment of large apocrine hidrocystomas with TCA is an effective and expeditious method of treating these disfiguring and recalcitrant lesions.

Aged↗

Mouse liver microsomal metabolism of chloral hydrate, trichloroacetic acid, and trichloroethanol leading to induction of lipid peroxidation via a free radical mechanism.

Metabolism of chloral hydrate (CH) by male B6C3F1 mouse liver microsomes (control-microsomes) generated free radical intermediates that resulted in endogenous lipid peroxidation, forming malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), acetone, and propionaldehyde. Because MDA, FA, and ACT are tumorigens, endogenous formation of lipid peroxidation products via a free radical mechanism may be responsible for hepatocellular tumorigenicity of CH to the B6C3F1 mice. Trichloroacetic acid (TCA) and trichloroethanol (TCE), the primary metabolites of CH, also generated free radicals and induced lipid peroxidation. Lipid peroxidation from TCA equaled that induced by CH, whereas that from TCE was 3- to 4-fold lower, suggesting that metabolism of CH to TCA may be the predominant pathway leading to lipid peroxidation. Metabolism of CH, TCA, and TCE by liver microsomes of mice pretreated with pyrazole (pyrazole-microsomes) yielded lipid peroxidation products at a level 2- to 3-fold higher than those from liver microsomes of untreated mice. In addition, CH-induced lipid peroxidation catalyzed by control-microsomes and pyrazole-microsomes was reduced significantly by 2,4-dichloro-6-phenylphenoxyethylamine, a general cytochrome P450 inhibitor. Thus, our study suggests that cytochrome P450 is the enzyme catalyzing the metabolic activation of CH and its metabolites (TCA and TCE) leading to lipid peroxidation, and that CYP2E1 may be the major isozyme responsible. This latter conclusion was supported by results using human lymphoblastoid cells expressing cytochrome P4502E1, which metabolized CH to reactants inducing mutations, whereas the parental cell line was inactive.

Allopurinol↗

Activation and attenuation of apoptosis of CD4+ T cells following in vivo exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and trichloroacetic acid.

Exposure to occupationally relevant concentrations of the environmental pollutant, trichloroethylene (TCE), in the drinking water of autoimmune-prone MRL+/+ mice has been shown to promote the generation of lupus and autoimmune hepatitis in association with the activation of Interferon-gamma (IFN-gamma)-producing CD4+ T cells. Since blocking TCE metabolism suppressed the TCE-induced alteration in immune function, the present study was initiated to determine whether the major metabolites of TCE, trichloroacetaldehyde hydrate (TCAH) and trichloroacetic acid (TCA) could also mediate these immunoregulatory affects in vivo. TCAH and TCA were administered to the drinking water of MRL+/+ mice for 4 weeks. CD4+ T cells from TCAH and TCA-treated MRL+/+ mice, unlike CD4+ T cells from control mice, demonstrated functional and phenotypic signs of activation, as evidenced by increased IFN-gamma production in association with the increased percentage of CD62L(lo) CD4+ T cells. Interestingly, it was also found that the CD4+ T cells from the TCAH and TCA-treated mice showed a decreased susceptibility to the activation-induced cell death (AICD) form of apoptosis following re-stimulation in vitro. By demonstrating that TCAH and TCA can activate CD4+ T cells and inhibit their apoptosis following in vivo exposure represents a mechanism by which environmental toxicants may induce or accelerate the development of autoimmune disease.

Animals↗

Environmental risk assessment of airborne trichloroacetic acid--a contribution to the discussion on the significance of anthropogenic and natural sources.

In environmental risk assessments the question has to be answered, whether risk reduction measures are necessary in order to protect the environment. If the combination of natural and anthropogenic sources of a chemical substance leads to an unacceptable risk, the man-made emissions have to be reduced. In this case the proportions of the anthropogenic and natural emissions have to be quantified. Difficulties and possible solutions are discussed in the scope of the OECD- and EU-risk assessments of trichloroacetic acid (TCA) and tetrachloroethylene. In the atmosphere, TCA is formed by photo-oxidative degradation of tetrachloroethylene (PER) and 1,1,1-trichloroethane. The available data on atmospheric chemistry indicate that tetrachloroethylene is the more important pre-cursor. With its high water solubility and low volatility, TCA is adsorbed onto aerosol particles and precipitated during rainfalls. Extended monitoring in rainwater confirmed the global distribution of airborne TCA. TCA reaches soils by dry and wet deposition. In addition formation of TCA from tetrachloroethylene in plants was observed. Consequently, high concentrations were detected in needles, leaves and in forest soil especially in mountain regions. The effect assessment revealed that plants exposed via soil are the most sensitive species compared to other terrestrial organisms. A PNECsoil of 2.4 microg/kg dw was derived from a long-term study with pine and spruce seedlings. When this PNEC is compared with the measured concentrations of TCA in soil, in certain regions a PEC/PNEC ratio >1 is obtained. This clearly indicates a risk to the terrestrial ecosystem, with the consequence that risk reduction measures are deemed necessary. To quantify the causes of the high levels of TCA in certain soils, and to investigate the geographical extent of the problem, intensive and widespread monitoring of soil, air and rainwater for TCA and tetrachloroethylene would be necessary to be able to perform a full mass balance study at an appropriate number of sites. In addition, measurements of the 14C content in TCA isolated from soil could clarify whether a significant proportion of the TCA occurs from natural sources. The possible formation of TCA in soil can also be tested by incubation of isotope enriched inorganic chloride with subsequent mass spectrometry of TCA.

Carbon Isotopes↗

Trichloroacetic acid accumulates in murine amniotic fluid after tri- and tetrachloroethylene inhalation.

The distribution of trichloroethylene (Tri) and tetrachloroethylene (Tetra) and their metabolites have been studied in pregnant mice by means of whole-body autoradiography (14C-labelled Tri and Tetra) and gas chromatography, with special emphasis on possible uptake and retention in the foetoplacental unit. Volatile (non-metabolized) activity appeared at short intervals after a 10 min. or 1 hr inhalation period in foetus and amniotic fluid. Most notable, however, was a strong accumulation and retention (peak at 4 hrs) in amniotic fluid of the metabolite trichloroacetic acid (TCA) after inhalation of either of the solvents. The main metabolite of Tri, trichloroethanol (TCE) (or conjugates), did not accumulate specifically as compared to maternal plasma. TCA infused intravenously in the maternal plasma was accumulated in amniotic fluid, but less pronounced than after Tri and Tetra inhalation, indicating that some metabolism of Tri and Tetra to TCA may occur in the foetoplacental unit. The results suggest that TCA may be transported to the foetus partly paraplacentally through foetal membranes and amniotic fluid, with the possibility of foetal swallowing or absorption through the skin. Foetal urinary activity also suggests that circulation between foetus and amniotic fluid may contribute to the long-term retention in the foetoplacental unit. In the mother, after inhalation exposures, and in intraperitoneally injected newborn mice, non-extractable radioactivity was found in the respiratory tract, liver, and kidney, indicating binding to these organs through metabolism.

Amniotic Fluid↗