Document Dvg1y3zaKJNrb4xJR7x22gJ0d

TOXICOLOGY AND APPLIED PHARMACOLOGY 91, 256-265 (1987) 1C Intestinal Absorption of Trichloroeth''1'' p TATSUYA HOBARA, HaRUO KOBAYASHI, SUSUMU IWAMOTO, ANDTsi Department ofPublic Health. Yamaguchi University School ofl, (j'V-1 C; \ ]dert&u Received November 24, 1986; accepted. Intestinal Absorption of Trichloroethylene in Dogs. Hobara, T., Kobayashi, H., Kawa moto, T., Iwamoto, S., and Sakai, T. (1987). Toxicol. Appl. Pharmacol. 91,256-265. In order to examine the intestinal absorption of trichloroethylene (TRI), we developed the intestinal circulation system ofdogs and administered TRI solution at three concentrations (0.1,0.25 and 0.5%) to the three parts ofthe intestinal tract (jejunum, ileum, and colon) of the operated dogs. We measured TRI and its metabolites, free-trichloroethanol, trichloroacetic acid, and conju gated trichloroethanol, in serum or blood, urine, bile and circulating solutions. The absorption rates of TRI from the intestine were 50-70% of the administered volume of TRI 2 hr after administration in all groups, and all parts of intestine readily absorbed TRI. Moreover, there were no significant differences in the absorption rates of TRI and water between the jejunum and ileum, and ileum and colon, respectively. The excretion rates of TRI and its metabolites in urine and bile were very low (0.1-0.4%) compared with the volume of absorbed TRI from the intestine 2 hr after administration in all groups. The high degree ofabsorption ofTRI should be considered when threshold limits for TRI in the drinking water, the surface water, and the ground water are established. \<m Academic Press, inc. An important industrial chemical for the past 60 years, trichloroethylene (TRI)1 is used as a solvent for vapor decreasing of fabricated metal parts, as a solvent in the textile indus try, and as a lubricant, among other uses. There are numerous surveys concerning TRI toxicity to animals and humans (Waters et al, 1977; Nomiyama and Nomiyama, 1979; Kimbrough et al., 1985). In recent years, it is reported that this substance is a carcinogen in B6C3F1 mice (NCI, 1976; NTP, 1983). TRI production by chemical companies has been increasing every year. During and after use, large amounts of TRI are released into rivers, the ground, and the sea. TRI is a 1 Abbreviations used: TRI, trichloroethylene; CH, chloral hydrate; F-TCE, free trichloroethanol; ConjTCE, conjugated trichloroethanol; TCA. trichloroacetic acid;T-TCE, total trichloroethanol; ECO, electrocardio gram. stable substance that is only slightly degraded by light, heat, water, natural bacteria, and mi croorganisms. It has a slow decomposition rate in the dark in dilute aqueous solution (Dilling et al, 1975). Therefore, TRI pollu tion of surface water as well as ground water is increasing year by year, creating serious problems in many advanced nations (IARC, 1979). In contrast, relatively little is known about its absorption from the gastrointestinal tract (D'Souza et al, 1985). For this reason, we administered TRI solutions at three con centrations (0.1,0.25, and 0.5%) to the three segments of intestinal tracts (jejunum, ileum, and colon) of operated dogs. We measured TRI and its metabolites, free trichloroethanol (F-TCE), trichloroacetic acid (TCA), and conjugated trichloroethanol (Conj-TCE), in the serum or blood, urine, bile, and circulat ing solutions. 0041-008X/87 $3.00 Copyright 1987 by Academic Press. Inc. All rights ofreproduction in Any form reserved 256 Ik s' SL 032738 1 TOXICOLOGY AND APPLIED PHARMACOLOGY 91, 256-265 (1987) Intestinal Absorption of Trichloroethylene in Dogs Tatsuya Hobara, Haruo Kobayashi, Toshihiro Kawamoto, SUSUMUIWAMOTO, AND TSUNEMI SAKAI Department ofPublic Health, Yamagucht University School ofMedicine. 1144 Kogushi, Ube 755, Japan Received November 24,1986; accepted July 14,1987 Intestinal Absorption of Trichloroethylene in Dogs. Hobara, T., Kobayashi, H., Kawa moto, T., Iwamoto, S., and Sakai, T. (1987). Toxicol. Appl. Pharmacol. 91,256-265. In order to examine the intestinal absorption of trichloroethylene (TR1), we developed the intestinal circulation system ofdogs and administered TRI solution at three concentrations (0.1,0.25 and 0.5%) to the three parts of the intestinal tract (jejunum, ileum, and colon) of the operated dogs. We measured TRI and its metabolites, free-trichloroethanol, trichloroacetic acid, and conju gated trichloroethanol, in serum or blood, urine, bile and circulating solutions. The absorption rates of TRI from the intestine were 50-70% of the administered volume of TRI 2 hr after administration in all groups, and all parts of intestine readily absorbed TRI. Moreover, there were no significant differences in the absorption rates of TRI and water between the jejunum and ileum, and ileum and colon, respectively. The excretion rates of TRI and its metabolites in urine and bile were very low (0.1-0.4%) compared with the volume of absorbed TRI from the intestine 2 hr after administration in all groups. The high degree ofabsorption ofTRI should be considered when threshold limits for TRI in the drinking water, the surface water, and the ground water are established. 1987 Academic Pres, lnc. % \ ^ An important industrial chemical for the past 60 years, trichloroethylene (TRI)1 is used as a solvent for vapor decreasing of fabricated metal parts, as a solvent in the textile indus try, and as a lubricant, among other uses. There are numerous surveys concerning TRI toxicity to animals and humans (Waters et al., 1977; Nomiyama and Nomiyama, 1979; Kimbrough et al., 1985). In recent years, it is reported that this substance is a carcinogen in B6C3F1 mice (NCI, 1976; NTP, 1983). TRI production by chemical companies has been increasing every year. During and after use, large amounts of TRI are released into rivers, the ground, and the sea. TRI is a 1 Abbreviations used: TRI, trichloroethylene; CH, chloral hydrate; F-TCE, free trichloroethanol; ConjTCE, conjugated trichloroethanol; TCA. trichloroacetic acid; T-TCE, total trichloroethanol; ECG, electrocardio gram. stable substance that is only slightly degraded by light, heat, water, natural bacteria, and mi croorganisms. It has a slow decomposition rate in the dark in dilute aqueous solution (Dilling et al,, 1975). Therefore, TRI pollu tion of surface water as well as ground water is increasing year by year, creating serious problems in many advanced nations (IARC, 1979). In contrast, relatively little is known about its absorption from the gastrointestinal tract (D'Souza et al,, 1985). For this reason, we administered TRI solutions at three con centrations (0.1,0.25, and 0.5%) to the three segments of intestinal tracts (jejunum, ileum, and colon) of operated dogs. We measured TRI and its metabolites, free trichloroethanol (F-TCE), trichloroacetic acid (TCA), and conjugated trichloroethanol (Conj-TCE), in the serum or blood, urine, bile, and circulat ing solutions. 0041-008X/87 $3.00 Copyright 1987 by Academic Press, Inc. All rights of reproduction in any form reserved. 256 SL 032739  >ogs AMOTO, ishi, Ube 755, Japan ABSORPTION OF TRICHLOROETHYLENE IN DOGS abdominal cavity 257 SHI. H., Kawa^6-265. In order d the intestinal ns (0.1,0.25 and e operated dogs. ;cid. and conjuThe absorption ' TRI 2 hr after ^toreover. there ^^Mhe jejunum ^metabolites in d TRI from the T TRI should be water, and the inly slightly degraded ural bacteria, and mislow decomposition nte aqueous solution herefore, TRI polluwell as ground water ear, creating serious need nations (IARC, lively little is known n the gastrointestinal >85), For this reason, ilutions at three connd 0.5%) to the three acts (jejunum, ileum, dogs. We measured free trichloroethanol c acid (TCA), and anol (Conj-TCE), in e, bile, and circulat- INCUBATOR Fig, 1. Intestinal circulation system. _l i <uoz_>> TIME (HOUR) Fig. 2. Trichloroethylene concentrations in the blood after administration of 0.1,0.25, and 0.5% trichloroeth ylene solution (mean SD; n = 5). ' , Jejunum; O, il eum; A, colon, a. Significant difference between the jeju num and colon (p < 0.05). c. Significant difference be tween the ileum and colon (p < 0.05). Fig. 3. Free trichloroethanol concentrations in serum after administration of 0.1, 0.25, and 0.5% trichloroeth ylene solution (mean SD; n = 5). 0, Jejunum; O, il eum; A, colon, a. Significant difference between the jeju num and colon (p < 0.05). b, Significant difference be tween the jejunum and ileum (p < 0.05). SL 32740 258 HOBARA ET AC TABLE 1 Gas Chromatographic Operating Conditions for Analysis of Trichloroethylene, Trichloroethanol, and Trichloroacetic acid (Shimadzu GC-7AG with Flame Ionization Detector (FID) and Elec tron Capture Detector (ECD)) Column Column packing Oven Injection temperature temperature Carrier gas and flow rate Detector Trichloroethylene Trichloroethanol and trichloroacetic acid 3.0 mm 4> X 2.0 m (glass) 3.2 mm <t> X 2.0 m (glass) 25% Silicone DC-550 Celite 545 AW 6080 mesh 5% OV-17 Gaschrom Q 100-120 mesh 150*C 110'C 170'C 180*C N:, 60 FID ml/min N2,40 ECD ml/min (Ni-63) METHODS Animals. Sixty adult male and female mongrel dogs (8-12 kg body wt) were used. Each dog was anesthetized with 25-30 mg/kg of sodium pentobarbital given intra venously. Tracheal intubations were performed and can nulas were connected with a volume-type respirator (Aika-R-60). The respiratory rate was 20 cycles/min, and Fig. 4. Conjugated trichloroethanol concentrations in serum after administration ofO. 1,0.25. and 0.5% trichlo roethylene solutions (mean SD; n = 5). 0, Jejunum; O, ileum; A, colon, a. Significant difference between the jejunum and colon (p < 0.05). c. Significant difference between the ileum and colon (p < 0.05). Fig. 5. Trichloroacetic acid concentrations in serum after administration of 0.1, 0.25, and 0.5% trichloroeth ylene solutions (mean SD; n = 5). 0, Jejunum; O, il eum; A. colon, a. Significant difference between the jeju num and colon (p < 0.05). c. Significant difference be tween the ileum and colon (p < 0.05). SL 032741 V Carrier gas and e flow rate Detector Nj, 60 FID ml/min N2,40 ECD ml/min (Ni-63) > pentobarbital given intrais were performed and can. olume-type respirator (Aite was 20 cycles/min, and ABSORPTION OF TRICHLOROETHYLENE IN DOGS 259 cm retrograde from the ileocecal region, and the colon was defined as the first 30 cm from the ileocecal region. Phosphate buffer solution was circulated with a rotary pump (Travenol Co.) at 300 ml/min. After the solution had circulated to the intestine, the abdominal wall was closed and both sides ofthe tubes were left in place. Then solutions containing 0.1, 0.25, or 0.5% (weight/volume) were perfused through the intestine. At concentrations of TRI below 0.1 %, we could not measure F-TCE and TCA in blood, urine, or bile. The volume ofeach solution was 500 ml. TRI was added to polyoxyethylene sorbitan monooleate (Tween 80,1:1) and adjusted to pH 7,0 with a phosphate buffer. These mixed solutions were soluble in water. TRI and Tween 80 were obtained from Katayama Chemical Co., Inc., and had a purity of more than 99%. Sampling of blood, urine, bile, and solution. Arterial blood samples (6 ml) were obtained From the right femo- -r * 1.5 : (HOUR) 2 .0 oncentralions in serum and 0.5% trichloroeth- 5). , Jejunum: O. il* rence between thejeju- gmtieant difference bei.05). j. 6. Free trichloroethanol concentration in urine afiministration of 0.1, 0.25, and 0.5% trichloroethylolutions (mean SD; n = 5). 0, Jejunum; O, ileum: olon. a. Significant difference between the jejunum . colon (p < 0.05). b, Significant difference between - jejunum and ileum (p < 0.05), c. Significant differ* ,e between the ileum and colon (p < 0.05). .idal volume was adjusted to yield a peak inspiratory pressure of 10 cm HjO(Kobayashi et ai, 1984). A catheI-t was inserted into the left femoral artery and con nected to a strain-gauge transducer (Nihon Roden MP0.5) to measure arterial blood pressure. The electrocar diogram (ECG) was recorded from the three standard limb leads and monitored with a memory scope (Nihon Koden VM-645R). The heart rate was obtained from the R-R interval in the ECG. Intestinal circulation system. As shown in Fig. 1, the abdominal wall was cut transversely along the bottom of the diaphragm with an electric surgical unit (Asahiika Co.). After the intestine was cut at a length of 30 cm, the contents were emptied and the inside was washed with a % phosphate buffer (pH 7.0). Both sides of the intestine were connected with Teflon tubes (1 cm <t> X 40 cm), as shown in Fig. 1, and the opposite sides of the intestine were closed. The jejunum, ileum, and colon were used for TRI administration. The jejunum was defined as the first 30 cm after the stomach, the ileum was defined as 30 FlG. 7. Conjugated trichloroethanol concentration in urine after administration of 0.1,0.25, and 0.5% trichlo roethylene solutions (mean SD; n = 5). 0, Jejunum; O, ileum; A, colon, a. Significant difference between the jejunum and colon (p < 0.05). c, Significant difference between the ileum and colon (p < 0.05). SL 032742 260 HOBARA ET AL. Statistical analysis. All data are presented as the mean standard deviation of the mean. The data were com pared by ANOVA and Newman-Keul's test. p values < 0.05 were regarded as significant. RESULTS Intestinal Circulation System The intestinal circulation system did not result in significant differences in blood pres sure, heart rate, ECG, glutamic oxaloacetic transaminase and glutamic pyruvic transami nase, alkaline phosphatase, erythrocyte and leukocyte counts, hematocrit, blood urea ni trogen, and creatinine. Moreover, no abnor mal findings were observed in the ECG pat tern. This operation does not require special- Fig. 8. Trichloroacetic acid concentration in urine af ter administration of 0.1. 0.25, and 0.5% trichloroethyl ene solutions (mean SD; n = 5). 0. Jejunum; O, ileum; A. colon, a. Significant difference between the jejunum and colon (p < 0.05), ral artery once before administration of TRI and at 30, 60,90, and 120 min after administration. Urine was col lected with a urinary catheter, which was inserted through the urethra into the bladder (Hobara et at., 1986a). Urine was collected five times, from 30 min be fore administration to 2 hr after administration. Bile was collected every 30 min until 2 hr after administration of each concentration ofTRI (Hobara et at.. 1982b, 1986b). Three-milliliter samples ofthe circulating solutions were collected from the outlet (Fig. 1) every 30 min until 2 hr after administration. The volume of excreted unne and bile was constant for all TRI groups, about 1.0 ml/kg/hr. Analysis. The analytical methods for the determina tion of F-TCE. total trichloroethanol (T-TCE) contain ing F-TCE and Conj-TCE, and TCA were described by Humbert and Fernandez (1976). Conj-TCE was calcu lated from the differences between T-TCE and F-TCE. The method for determining TRI has been described pre viously (Hobara it ai. 1982a). F-TCE, T-TCE. and TCA were measured periodically in the serum, urine, bile, and solution, while TRI was measured in the blood, urine, bile, and solution. The gas chromatographic conditions are shown in Table 1. Fig. 9. Trichloroethylene concentration in bile after administration of 0.1, 0.25, and 0.5% trichloroethylene solutions (mean SD; n = 5). 0, Jejunum; O, ileum; A, colon, a, Significant difference between the jejunum and colon ip < 0.05). c. Significant difference between the ileum and colon (p < 0.05). SL 032743 ta are presented as the mean. The data were vman-Keul's test, p vi--1 ificant. JLTS System lation system did not erences in blood presglutamic oxaloacetic mic pyruvic transami.tase, erythrocyte and ttocrit, blood urea niMoreover, no abnorrved in the ECG pat es not require special- ABSORPTION OF TRICHLOROETHYLENE IN DOGS 261 0.1% colon group was higher than those in the il eum and jejunum groups, while the F-TCE and Conj-TCE levels of the jejunum were higher than those of the colon and ileum. TCA levels in the jejunum and ileum were higher than that of the colon. Absorption of TRI, F-TCE, TCA, and Conj-TCE increased with increasing concentrations of TRI, but the increases were not proportional to the in creases in TRI concentration in the perfusing solutions. 0.5% Changes ofTRI and Its Metabolites in Urine, Bile, and Circulating Solution 0.5 1.0 1.5 2.0 TIME (HOUR) 10. Free trichloroethanol concentration in bileafnmistration of 0.1, 0.25, and 0.5% trichloroethyl- lutions(mean SD; n = 5). 0, Jejunum; O, ileum; on. Figures 6, 7, and 8 show the changes in FTCE, Conj-TCE, and TCA in the urine, re- ncentraiion in bile after I 0.5% trichloroethylene . Jejunum: O. ileum; A. etween the jejunum and difference between the j surgical techniques and takes 10-20 min j omplete. | ' anges in TRI and Its Metabolites in Blood >r Serum | Figures 2, 3. 4, and 5 show the changes in j 1RI, F-TCE. Conj-TCE, and TCA in the blood or serum after administration of 0.1, 0.25, and 0.5% TRI through the jejunum, il eum, and colon. TRI values were measured in the blood, while those of F-TCE, TCA, and Conj-TCE were measured in the serum, j According to these observations, TRI re mained constant in the blood, while F-TCE, Conj-TCE. and TCA increased gradually with time. Depending on the time, the con Fig. 11. Conjugated trichloroethanol concentration in centration of TRI was 10 to 30 times higher than those of F-TCE, Conj-TCE, and TCA in all groups. In terms ofeach region ofadminis tration, the blood concentration ofTRI in the bile after administration of0.1,0.25, and 0.5% trichloro ethylene solutions (mean SD; n = 5). 0, Jejunum; O, ileum; A, colon, a. Significant difference between the je junum and colon (p < 0.05). c. Significant difference be tween the ileum and colon (p < 0.05). SL 0327^ 262 HOBARA ET AL. Conj-TCE were dramatically higher than those of F-TCE and TCA. In terms of the bil iary excretion of TRI and its metabolites, the region of administration was jejunum > il eum > colon. Concentration dependency was observed. Figure 13 shows the changes in the concen tration of TRI in the circulating solutions af i teradministration ofO. 1,0.25, and 0.5% TRI. The decrease in TRI concentration over time was linear. No apparent differences could be observed with respect to the region of admin CA coZj istration. Absorption and Excretion ofthe TRI and Its Metabolites The data in Table 2 show that 10% of the water and 50-70% of TRI were absorbed in Fig. 12. Trichloroacetic acid concentration in bile af ter administration of 0.1, 0.25, and 0.5% trichloroethyl ene solution (mean SD; n = 5). 0, Jejunum; O, ileum; A, colon, a, Significant difference between the jejunum and colon (p < 0.05). c, Significant difference between the jejunum and ileum (p < 0.05). spectively, after circulation of 0.1, 0.25, and 0.5% TRI through the jejunum, ileum, and colon. F-TCE, Conj-TCE, and TCA in creased with time of perfusion in all urine samples. The levels of Conj-TCE were much higher than those of F-TCE or TCA. TRI was not detected in the urine. Urine levels of F-TCE, Conj-TCE, and TCA ranked with respect to region of administration were jeju num > ileum > colon. Urinary concentra tions of metabolites increased as the concen tration of TRI increased. Figures 9, 10, 11, and 12 show changes in TRI, F-TCE, Conj-TCE, and TCA in the bile after administration of 0.1, 0.25, and 0.5% TRI. TRI decreased, F-TCE remained con stant, and TCA and Conj-TCE increased with time ofperfusion. The concentrations of TIME (HOUR) Fig. 13. Trichloroethylene concentration in circulat ing solutions after administration of 0.1,0.25, and 0.5% trichloroethylene solutions (mean SD; n = 5). 0, Jeju num; O, ileum; A, colon. SL 032745 atically higher than A. In terms of the bif id its metabolites, the n was jejunum > il* ntration dependency hanges in the concenculating solutions af,0.25, and 0.5% TR1. icentration over time i differences could be > the region ofadmin- m ofthe TRI and Its how that 10% of the RI were absorbed in '5 (HOUR) 2.0 icentration in circulat or 0.1, 0.25. and 0.5% i SD; n = 5). 0, Jeju- ABSORPTION OF TRICHLOROETHYLENE IN DOGS 263 TABLE 2 sorption Rates of Trichloroethylene (TRI) \ Water in the Jejunum. Ileum, and Colon 2 hr r Administration of TRI and Phosphate 1 er (Control) ( Mean SD; n = 5). ion and lution Percentage absorbed Water TRI num jntrol 1% TRI 25% TRI 5% TRI 11.3 + 2.6 9.8 1.9 10.1 2.8 9.2 2.4 -- 56.1 15.3 67.4 21.2 61.3 15.7 ontrol '.1% TRI ).25% TRI ).5% TRI 'Ion Control 0.1% TRI 0.25% TRI 0.5% TRI 9.0 2.1 10.6 3.7 9.8 3.1 8.8 2.2 12.1 2.9 9.9 1.4 10.1 2.3 10.6 2.7 -- 64.2 14.8 59.6 12.3 57.8+13.0 -- 59.3+11.0 61.8 15.7 56.4+ 13.2 DISCUSSION In the present study, we found no signifi cant differences in the biological and physio logical parameters before and after operation in the anesthetized dogs. Moreover, the respi ratory rate and tidal volume were controlled by the respirator. Thus, we believe the results obtained in this model are comparable to those anticipated in normal dogs. It is well known that the intestinal absorp tion rates of substances are different in different segments of the intestine. Some sub stances are well absorbed in the stomach or the jejunum and others are better absorbed from the colon or the ileum (Yoshimura and Ogata, 1970). Because of this, we investigated TRI absorption rates from the three segments of the intestine. No significant differences among the three segments of the intestine were found with respect to the absorption rate of TRI. However, blood concentrations 3 hr. These values were calculated from the difference between the original concentration and that at 2 hr. No significant differences were observed between the different regions of the intestine or between different TRI con centrations. The amount of TRI absorbed was about 5 mg/intestine (cm)/hr in the 0.1% TRI groups, 12-15 mg in the 0.25% TRI groups, and 20-24 mg in the 0.5% TRI groups, respectively. Moreover, that of water was 0.8 ml/intestine (cm)/hr in all regions. Table 3 shows the percentage of excretion to the absorbed TRI from the intestine in the urine and bile 2 hr after administration. The amount of urine and bile excreted was con stant in all groups, i.e., about 1 ml/kg hr. The total excretion of TRI and its metabolites in bile and urine during the 2-hr experiment, was 0.3-0.4% of the absorbed TRI for the je junum, 0.2-0.3% for the ileum, and 0.1 -0.2% for the colon. More than 90% of the biliary and urinary metabolites were in the form of Conj-TCE in all groups. table 3 Cumulative Excretion Ratio of Trichloro ethylene (TRI) and Its Metabolites to the Ab sorbed AMOUNTS OF TRI FROM THE INTESTINE IN THE Bile and urine 2 hr after Administration of TRI (Mean; n- 5) Region and solution Cumulative excretion ratio to absorbed amounts of TRI at 2 hr Urine (%) Bile (%) Jejunum 0.1% TRI 0.25% TRI 0.5% TRI Ileum 0.1% TRI 0.25% TRI 0.5% TRI Colon 0.1% TRI 0.25% TRI 0.5% TRI 0.26 0.15 0.19 0.15 0.12 0.13 0.09 0.07 0.08 0.17 0.09 0.11 0.11 0.08 0.07 0.06 0.04 0.04 264 HOBARA et al. of TRI were higher following absorption from the colon than from the ileum and jeju num. This situation was reversed for the TRI metabolites. These data indicate that TRI metabolism was different in each absorptional segment of the intestine and that the intestine itself might play some part in TRI metabolism. D'Souza et al. (1985) administered TRI in travenously and orally to the rats and mea sured TRI in the blood over time. They re ported that TRI was rapidly absorbed after oral dosing, with blood concentrations peak ing between 6 and 10 min. It was suggested that TRI was probably absorbed through gas trointestinal membranes by passive diffusion, since it was a small, unchanged, lipid-soluble molecule. In our present examination, all seg ments of the intestine readily absorbed TRI and the blood TRI concentration was con stant at 2 hr. The decrease in TRI concentra tion over time was linear in the circulating so lution. We could not determine if TRI was absorbed passively in our system. Since TRI is a lipophilic substance, the lymphatic sys tem of the intestine might play a major role in the absorption of TRI. In our previous reports, about 50% of the absorbed TRI was excreted in expired air in 1 hr after exposure to TRI (Hobara et al., 1982a). The percentage ofTRI and its metab olites in urine to the total amount of TRI ab sorbed by the lungs was about 0.7% at 1 hr after TRI exposure (Hobara et al.. 1983). These figures indicated that absorbed TRI is partly excreted into the expired air, while its metabolites (F-TCE, TCA, Conj-TCE, and others) are excreted into the urine and bile (Dekant et al., 1984; Green and Prout, 1985), Moreover, excretion of TRI into bile was ob served in this study as well as in our previous studies (Hobara et al., 1982b, 1986b). There are many differences among the species in TRI metabolism (Mueller et al., 1982; Prout et al., 1985). Therefore, the data obtained in these animals studies may not directly be ap plied to humans. TRI has been identified as a water contami nant in several water supplies surveyed by the U.S. EPA, The contaminating levels of TRI in the drinking water are generally in the low ppb. However, it is likely that TRI is readily absorbed by humans. This factor must be considered in calculating human risk from TCE exposure. REFERENCES Dekant, W,, Metzler, M., andHenshler, D. (1984). Novel metabolites of trichloroethylene through de chlorination reactions in rats, mice and humans. Biochem. Pharmacol. 33, 2021-2027. Dilung, w. l., Tefertiller, N. B., and George, J. K. (1975). Evaporation rates and reactivities of methylene chloride, chloroform, 1,1,1-trichioroethane, trichloroethylene and other chlorinated com pound in dilute aqueous solutions. Environ. Sci. Toxi col. 9,833-838. D'Souza, R. W,, Bruckner, J. V., and Feldman, S. (1985). Oral and intravenous trichloroethylene phar macokinetics in the rat. J. Toxicol. Environ. Health 15,587-601. EPA (1984). Health Assessment of Trichloroethylene, EPA 600/8-82-006B. U.S. Environmental Protection Agency, Washington, DC. Green, T., and Prout, M. S. (1985). Species differ ences in response to trichloroethylene in rats and mice. 11. Biotransformation in rats and mice. Toxicol. Appl. 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