Document OznO0z5Y5Q9oMZLzNgYGD2X11

ervr Jr COTOXICOLOGY AND ENVIRONMENTAL SAFETY 10, 281-289 (1985) Effect of Vinyl Chloride on Testis in Rats - Wenfang Bl Youshen Wang, Meiyuang Huang, and Deshan Meng Institute ofHealth, China National Centrefor Preventive Medicine, Beijing, People's Republic ofChina Received May 16, 1984 . A total of 300 male adult Wistar rats (180-220 g) were used. Animals were divided into four groups: control, vinyl chloride (VC) |0-, 100-, and 3000-ppm exposed groups. Seventy-five rats were used for each group. Inhalation exposure to VC was conducted 6 hr per day and 6 days per week. In the third, sixth, and twelfth month following exposure 8-30 rats of each group were killed. The others were under observation and sacrificed after 18 months. After exposure to VC, the organ and body weight ratio, such as the kidney, liver, spleen, and heart were increased, but those of the testis were decreased in the experimental groups in the sixth month. The differences between experimental groups and the control group were statistically significant (P < 0.05 or P < 0.01). The weights of testis were decreased and damage of testicular seminiferous tubules were found in rats by histopathological examination. Incidence of damage of testicular seminiferous tubules in the control, 10-, I00-, and 3000-ppm groups were 18.9, 29.7, 36.5, and 56.0%, respec tively. There was an obvious dose-response relation between the concentration of VC and the incidence of testis damage, with a correlation coefficient of 0.993 (P < 0.01), Statistically, the incidence of damage of testicular seminiferous tubules in rats in the 3000-ppm group and in 100ppm group were significantly higher than that of the control group, respectively (P < 0.001 and P < 0.05). C !9S5 Acadtmtc Press, tnc. It is known that vinyl chloride (VC) is carcinogenic to animals. However, we have found that VC may induce testicular damage in rats in our exposure experiment. This finding has not been reported in the literature. The effect of VC on testicular lesion in rats is described in detail in this paper. MATERIAL AND METHODS Material. VC was provided by the Beijing Second Chemical Factory. The purity was 99.99% (the 0.01% impurities mainly consisted of the following chemicals: chloromethane, 1,3-butyldiene, propylene, monoethylene acetylene, water, and others.) Animals. A total of 300 adult Wistar rats weighting 180-220 g were used. They were randomly divided into four groups and received the following treatments, re spectively: control, vinyl chloride 10, 100, and 3000 ppm by inhalation. Rats per group (8, 30, 6, and 10) were killed at the third, sixth, ninth, and twelfth month, respectively, after the initial exposure. Surviving rats were killed at the 18th month (i.e., 6 months after discontinuing the exposure). Animals were weighed once per month before and after exposure and observed for symptoms twice a day."The diet and water was ad libitum. The diet was supplied by the Centre for Experimental Animals, Chinese Academy of Medical Sciences. The animals were kept in cages made of steel nets. Inhalation exposure. Customized six-angle cubic shaped glass dynamic chambers. :re employed for this study. These chambers permitted continuous observation during 281 0147-6513/85 S3.00 Copyright 1985 by Academic Press, Inc, AU right* of reproduction in any form reserved. I ASI 00004748 282 Bl ET AL. exposure and were designed to ensure uniform spatial distributions of gas mixtures introduced through the inlet port. Animals that inhaled VC 10, 100, and 3000 ppm .were put into the chambers of 2918, 774, and 388 liters, respectively. Dynamic in halation of VC was conducted for a 6-hr period per day and 6 consecutive days per week during the 12 months exposure period. The concentration of VC was determined by Sp-E2305-type gas chromatography (made in China, Beijing Analytic Instrument Factory). The conditions of the analysis are summarized in Table 1. The effluent value of entrance of VC into the three chambers (10, 100, and 3000 ppm) were 5.3, 20, and 330 ml/min, and for fresh air were 624, 132, and 87.2 ml/ min, respectively. According to calculation, fresh air entering the chambers would meet the need for the animals of each group. Vinyl chloride concentration of the respiratory region of the animals in each chamber was evenly distributed. The range of change of VC concentration was within 5%. Thirty min after the beginning of the inhalation exposure, VC concentration in each chamber reached to 94% ofthe predicted value. For about 1 hr, VC concentration reached the predicted value. VC was provided for exactly 6 hr, followed with a supply of fresh air for another hour, then the animals were removed from the chambers. During the 12 months of inhalation, 30 air samples were taken randomly from each chamber (containing 10, 100, or 3000 ppm VC). During exposure, temperature and relative humidity inside and outside the chambers before and after exposure were recorded every day. The rats were deprived of food and water during exposure. Autopsies of dead or sacrificed rats were carried out. Testes, lungs, liver, heart, kidneys, spleen, and brain were examined visually for focal or generalized lesions and hemorrhage. The above-mentioned organs and tissues were subjected to microscopic examination. Tissue samples were fixed with 10% Formalin solution and embedded in paraffin. Sections were cut at 5 and stained with H & E. The testes were cut transversely and the pathological changes were graded according to the number of damaged testicular seminiferous tubules counted under the micro scope as follows (see Table 5): (1) 10-50 seminiferous tubules damaged (disappearance of spermatids, spermatocytes) was shown as (2) 50-100 seminiferous tubules damaged (disappearance of spermatids, spermatocytes) was shown as (3) more than 100 seminiferous tubules damaged (disappearance of spermatids, spermatocytes' was shown as "+++." " TABLE 1 Gas Chromatograph Conditions Instrument Column Temperature Carrier gas Detector Accuracy Model SP-E 2305 2 m X A mm i.d. SS 15% Apiezon M, coated onto 40- to 60-mesh 6201 Column 80G--- - - Injector room temperature Detector 150C Type n2 Flow rate 36 ml/min FID 5 x 10"3 EFFECT OF VINYL CHLORIDE ON RAT TESTIS 283 RESULTS Concentration The range of change of VC concentration is shown in Table 2. As seen from Table 2, concentration of VC in the chamber was evenly distributed. Mean (SD) of VC the concentration of 30 air samples from each chamber (con taining 10, 100, or 3000 ppm VC) were 11.1 l.l, 105.6 13.9, and 2918 190 ppm, respectively. - The concentration of VC was constant during 6 hr of exposure. The range of change of the concentration in the chamber was within 3.3% (Fig. 1). The average temperature in the chambers of 10, 100, and 3000 ppm VC were 1.43, 2.07, and 3.01C higher than that outside the chambers and the average relative hu midity was 4.95, 4.64, and 0.18%. Body Weight The body weight attained by the animals of all experimental groups and the control group are shown in Fig. 2. Body weight attained by the animals of the two higher dose groups (100 and 3000 ppm) fluctuated during the 18-month period, but the values were less than that of the control group (P < 0.05 and P < 0.01). After 3, 6, 12, and 18 months since the start of exposure to VC, the organ and body weight ratio for kidney, liver, spleen, and heart in rats increased but those of the testes ^creased in the 100- and 3000-ppm groups at the sixth month (Table 3). Tumors Induced by VC Various tumors in rats induced by inhalation of VC for 18 months are shown in Table 4. Comparison of the incidence of tumors in the 3000- or 100-ppm group with TABLE 2 VC Concentration Measured at the Respiratory Regions of Eight Animals IN THE 10-ppm Chamber VC distribution at different levels in the !0-ppm chamber VC distribution in different directions in the 10-ppm chamber Level Points of samples VC concn (ppm) Avg concn (ppm) Direction Points of samples VC concn (ppm) Avg concn (ppm) Upper respiratory region Lower respiratory region A B C D A' B' C V 9.9 9.9 9.6 9.6 9.7 10.0 9.5 9.7 9.75 9.72 Northeast Northwest Southeast Southwest A A' B B' C C D V 9.9 9.7 9.9 10.0 9.6 9.5 9.6 9.5 9.80 9.95 9.55 9.65 284 BI ET AL. Slop 4 2 34 5 6 Time (hour) FlG. I, Range of change of VC concentration in the chamber during 6 hr of exposure. that ofthe control showed a statistically significant difference (P < 0.001). The difference in the incidence of angiosarcoma between the 3000-ppm group and the control group was also statistically significant {P < 0.001). Damage of Testes Damage of testicular seminiferous tubules has been Found in rats. The main changes of seminiferous tubules in the early stage consisted of irregular vacuolation of cyto plasm, swelling of cells, condensing of nuclei into minute hyperchromatic masses, and sloughing of the spermatids into the lumen. Fusion of several spermatids into multinucleated forms may occur (Fig. 3). Spermatocytes can also fuse into giant cells. At first, spermatids in seminiferous epithelial cells disappeared. After the disappearance of spermatids, the secondary, primary spermatocytes were sloughed into the lumen of the tubules, and in general, regardless of the degree of damage, a few spermatogonia and the Sertoli cells also remained. Some parts of seminiferous epithelial cells disap peared, but the rest remained (Fig. 4). Degeneration and necrosis were found in some parts of seminiferous epithelial cells (Fig. 5). The distribution of microscopic change occurred haphazardly: some tubules had severe degenerative changes while in the nearby tubules the changes were minimal (Fig. 6). This distribution appeared to be random and was neither consistent nor obviously related to the distribution of vascular blood. Damage of testicular seminiferous tubules occurred in the center as well as the A- * * i* i i,,. I i * l * l 1 2 34 5 6 7 8 91011121314151617181920 IrthalationTime (Month) Fig. 2. Effect of long inhalation exposure to VC on body weight of rats. EFFECT OF VINYL CHLORIDE ON RAT TESTIS TABLE 3 Effect of VC on the Organ and Body Weight Ratio in Rats Time of exposure (month) Group _ ---- ^ Testes Organ and body wt ratio Kidney Liver Spleen Heart 3 Control 7.13 Expt 6 Control 6.41 - -- Expt 5.73fc~] ** 5.91r J 12 Control 5.49 Expt - 18 Control "5.77 Expt -- * Rais exposed to JO ppm, 1 Rats exposed to 100 ppm. c Rats exposed to 3000 ppm. * P < 0.05. ** P< 0.01. 5.79 6.49*** 5.81 5.83 6.86r-** 5.09 5.94*'* 29.61 27.96 31.93 34.51* * 47.08fJ 30.97 3 7.09 31.68 1.47 1.68r'* 1.39 1.51'* 1.34 3.02 3.26*'* 2.58 2.89~L 2.79rJ 2.57 1.34 2.66 ^peripheral part of testes. In the case of severe damage, normal seminiferous tubules Are scarcely found (Fig. 7). A dose-response relation has been shown between the ^wverity of the testicular seminiferous tubules and the exposure concentration of VC. The correlation coefficient is 0.993, P < 0.001 (Table 5). The incidence of damage of testicular tubules in the control, 10-, 100-, and 3000- ppm groups were 18.9, 29.7, 36.5, and 56.0%, respectively. And the incidence of damage of testicular seminiferous tubules in rats exposed to 100 and 3000 ppm of VC were significantly (P < 0.05 and P < 0.001) higher than that of the control animals. TABLE 4 Carcinogenesis of VC on Wistar Rats under Inhalation Exposure for 18 Months Target organ Group No. animals No. animals bearing tumors Incidence of tumor (%) Angio sarcoma Liver Lung Lung Nose Skin Other Control 10 ppm 100 ppm 3000 ppm 19 20 19 20 1 1/19(5.2) 0 0 1 10 0 1 1/20 (5.0) 0 0 1 10 0 11 11/19(57.9) 7 2 3 2 2 3 19 17/19(95.0) 17 9 4 1 1 1 X* " 10.962, P < 0.001. x1 = 31.405, P < 0.001. 286 BI ET AL. rtv.- V .** Vf1 <4 '-> JSJ a** .vrt iv \i *. * * . c\ V Fig. 3. Fusion of several spermatids into multinuclcated forms in"a rat exposed to 10 ppm V'C for 6 months. HiE, X200. DISCUSSION Ribelin et al. (1963) has studied the effect of cadmium, phytic acid, acetoglycerides, jojoba bean meal, naphthalene, /ranj-aconitic acid, and dialdehyde starch on the testes of animals and found that the pathological changes of the testes were of the same type regardless of the compounds exposed. The differences between animals fed different compounds have been no greater than the differences occurring in animals fed any one of these compounds at various levels or various lengths of feeding time. The findings in the present study show that the pathological changes found in the VC* exposed rats were very similar to that described by Ribelin. ft*** >3rr,' rv $v t W, ET Fig. 4. Disappearance of some parts of the seminiferous epithelial cells. Some spermatids sloughed into the lumen. The rat was exposed to 3000 ppm for 6 months. H & E, X200. ASI 00004753 hr"' EFFECT OF VINYL CHLORIDE ON RAT TESTIS 287 ' sA :;- < vr?1.v;tIT';, ^ ;> .. s > Fig. 5. Degeneration and necrosis in some parts of the seminiferous epithelial cells in the rat exposed to 10 ppm VC for 6 months. H & E, X*G0. According to the processedofdamage to the seminiferous epithelial cells, chemicals are divided into the following two categories: (1) Compounds which may cause damage to seminiferous epithelial cells in the order of the spermatids, secondary spermatocytes, primary spermatocytes, and spermatogonia include dichromochloropane, cadmium, naphthalene, acetoglycerides, frans-aconitic acid, phenacitine, analgen, fluoroacetam- hexachlorophene, DDT, bis(dich!oroacety!)diamines, thiouracil, and cyclohex- "iL-A-sa m -SS izL&s w ariui 'Ml.. Sf: 4 ` C' m fcVC.'i is*:: &r vV Fig. 6. Severe degenerative changes in some tubules in rats exposed to 100 ppm VC for 12 months. H&E, XI00. 'v . :i . ;S--' ..V " - 7' " : v . i S'- T"` ' .> '' 2V,V, ^ .-'V- ' .V ; -r- - V ^ i - -*v.; v i ... I ,\r-/ . w/v- +'--: 'V- --S.'*--\ ' \'.v'-'-> - ` . ?. r 'r v ' :' V;;^s: v :v ' ...- i 7- 1 . r ./ .' v3 .- ' - . ' " ` T:, J-y . - y Fic. 7. In the case of severe damage, normal seminiferous tubules were scarcely found. H & E, X100. ylamine (Ribelin et al., 1963; Heywood et al, 1978; Biava et al, 1978; Drobeck and Coulston 1962). The lesions produced by VC were similar to those produced by these compounds. (2) Compounds that affect the spermatogonia at first and the spermatids last, include some antitumor drugs and alky] agents which interfere with DNA synthesis (Heywood et al., 1978; Cheng Yunsu et al., 1965). . In 1981, Hatch reviewed the effect of VC on reproductive systems, and his conclusion was that "At present, there is no data which point unambiguously to a relation between VC and reproductive outcome." Sokal et al. (1980) studied the chronic toxic effect of VC on rats exposed to 50, 500, and 20000 ppm VC in the air for 10 months. Local"degeneration, necrosis, and TABLE 5 : Damage of Testes Induced by Different Concentrations of Vinyl Chloride Group No. animals Damage of testis + ++ +++ Total no. % Control 74 9 3 10 ppm 74 14 5 100 ppm 74 19 5 3000 ppm 75 29 8 2---7. 3 3' 5 14" 22 27 42 _ 18.9 29.7 36.5* 56.0** Note + - 10-50 depleted seminiferous tubules were found in a section.++ = 50-100 depleted seminiferous tubules were found in a section. ++ + = More than 100 depleted seminiferous tubules were found in a section. Correlation coefficient r = 0.993, P < 0.01. * P < 0.05. ** P <0.001. ASI 00004755 j EFFECT OF VINYL CHLORIDE ON RAT TESTIS 289 Jisorders of spermatogenesis in the seminiferous epithelial cells were found. However, a dose-response relationship between the changes in testes and concentration of VC was not found. Heywood et al. (1978) pointed out that testicular atrophy may be observed in about 20% of the control rats that had been fed for 2 years under normal conditions. He concluded that the effect of chemicals on testes can be demonstrated by the comparison of experimental results with that of the control and by the dose-response relationship. Our study of the effect of VC on testicular damage in rats is consistent with the con clusions of Heywood et al. We have found that 18.9% of the rats in the control group showed atrophy_of testicular seminiferous tubules. Damage of testes was increased as the concentration of VC was increased. Statistical tests of the correlation coefficient showed a positive correlation between the incidence of damage of testicular tubules and the concentration of VC. Damage of testes in rats was proved to be related to inhalation of VC___ _ _ We believe that the effectsof VC on the reproductive system deserve further study. ^ ACKNOWLEDGMENTS We thank Professor Li Yurui {hecrilical review of this manuscript. Ms. Luo Yushu and Geng Taibao carried out the inhalation exposure of rats. Ms. Meng Huilin prepared the histological sections. REFERENCES Biava, C. G. el al. (1978). The testicular morphology of individuals exposed to dibrontochloropropane. Exp. Mol Pathol 29, 448^58. iENG YUNSU el al. (1965). A comparison of the destructive effects of five antitumor agents on various Pnormal tissues in mice. Ac!a Pharmacol. Sm. 12, 606. "touLSTON, F. et at. (I960). The biologic actions of a new series of bis(dichloroacetyl)diamines, Toxicol. Appl Pharmacol 2, 715. Dp.obeck, H. P., and Coulston, F. (1962). Inhibition and recovery of spermatogenesis in rats, monkeys, and dogs medicated with bis(dich!oroacelyl)diammes. Exp. Mol. Pathol. 1, 251. Hatch, M. (1981). Power considerations in studies of reproductive effects of vinyl chloride and some structural analogs- Environ. Health Perspect. 41, 195. Heller, C G. et al (1961). Suppression of spermatogenesis and chronic toxicity in men by a new series of bis(dichIoroacety))diamincs. Toxicol. Appl. Pharmacol. 3, 1. Heywood, r etal. (1978). Assessment of testicular toxicity in laboratory animals. Environ. Health Perspect. 24, 73. Ribeun, W. E. et al. (1963). Atrophy of rat testis as index of chemical toxicity. Arch. Pathol 75, 229. SOitAL, J. A. et al (1980). Experimental studies on the chronic toxic effects of vinyl chloride in rats. J. Hyg. Epidemiol. Microbiol. Immunol. 24, 285. w up* ^ .3 ASI 00004756 whole blood (MB). An investigation was made into the distribution V incidence of testis damage, with a correlation coeff. of 0.993. of A1 between the plasma and the blood-cell compartment and on Statistically, the incidence of damage of testicular seminiferous the extent of binding of A1 to the blood cells in rats and dialyzed tubules in rats in the 3000-ppm group and in the 100-ppm group patients. AI was distributed between plasma and blood cells with wassignificantly higher than that of the control groum only very small quant, differences; binding of Al to blood cells was lcft9>Si737g Subacute toxicity of 1,1,1-trichlfi^oethane, noise, very weak and the A1P and A1B detns. had similar prognostic valu^i0 and thehwrombination in rats. Blohm, Mirjmla; Braun, Horst; for toxicity. Kaschny, jrSer; Schill, Walter; Jastorff><5ernd; Diehl, Horst 104; 63731a Effect of ammonia on some enzymes of the urea (Fachber. 1 PfiW/Elektrotech., Univ. BryKeh, D-2S00 Bremen. 33 cycle and ornithine aminotransferase in the brain. Swamy, M.; Fed. Rep. Ger.). ^fotoxicol. Environ. Jlaf. 1985, '0(3), 295-301 Prasad, M- S. K.; Sadasivudu, B. (Dep. Biochem., Osmania Med. (Eng). Parallel grohnsof rats simultaneously exposed to Coll., India'. Neirokhimiya 1985, 4(3), 296-300 (Russ). The defined conditions (:) tjfS^richlotJnhane (TCE) [71-55-6] vapor; activities of argininosuccinate synthetase (ASS) [9023-58-9], (ii) noise pollution of 90 declHqji^iit') their combination; and (n) a argininosuccinase (AS) [9027-34-3], arginase [9000-96-8], and control group without any exp^WThe vapor of TCE was applied ornithine aminotransferase (OAT) [9030-42-6] were investigated in at a concn. of 200 ppm/8J^5r of 20^0 ppm/12 h for 84 days each. different sections of the rat brain following i.p. administration of 0.8 The expts. were perfopHaTwith TCE Irhi 2 different com. sources. mmol NHOAc [631-61-8]/100 g (acute) and 0.6 mmol NH(OAc/100 One of those TCE^pfyxKs. caused effects aStie high dosage level in g administration (6 times with 1-interval; chronic). No significant terms of enhanced l^els of (1) the relative oPN^r to body wt; (ii) changes in the arginase and ASS activities were obsd. in all the 3 liver microsomal Motein content; (iii) liver microsonS^nonooxygenase sections of brain examd. (brain stem, cerebral cortex and cerebellum), [9038-14-6] acj^ity; and (iv) 3,4-dihydroxypkenylgly?t)^JZ343-i9-9] The AS activity' substantially decreased in the cerebellum both under excretion ir^Brine. Eight other physiol, and biochem/Ttaramelers acute and chronic NH3 intoxication. OAT markedly increased in the were notylfanged. The other TCE prepn. at the high do!*, both cerebellum during chronic and in the cerebral cortex during acute TCE Q^pns. at the low dose, and noise did not affect the intoxication from NHj. inyeaMgated parameters. 104: 63732b Effect of chromium on growth and utilization of MR. 63738h Pathomorphological changes in gills of fish fin= iron and manganese by oat. Singh, Vinay, Parmar, Ram Kumar gerlings (Cirrhina mrigala) by linear alkyl bcnzenesulfonate, (Dep. Agric. Chem. Soil Sci., R.B.S. Coll., Uttar Pradesh, 283105 Misra, Virendra; Lai, Hazari; Chawla, Geeta; Viswanathan, P. N. India). J. Indian Soc. Soil Sci. 1985, 33(2), 450-1 (Eng). (Ind. Toxicol. Res. Cent., Lucknow, 226 001 India). Eeotoxieol. A pot expts. on alk. sandy loam soil, oat plants treated with Cr (5-25 Environ. Saf. 1985, 10(3), 302-8 (Eng). Fish (Cirrhina mrigala) ppm) developed toxicity symptoms similar to those reported by S. C. fingerlings exposed to a 0.005 ppm (25% of median lethal concn.) Agarwala and C. P. Sharraa (1976) and had decreases in dry-matter concn. of detergents (linear alkyl henzenesulfonate) showed marked yield of 68.8% (5 ppm Cr) to 97.1% (25 ppm Cr) with respect to the behavioral changes and distorted appearance of primary and control. Thus, Cr addn. resulted in decreases in concn. and uptake secondary lamellae along with damage 10 gill epithelium under SEM of Fe and Mn by oat plants, although the decrease in Mn content at various magnifications. Mucosal cells of gills secreted mucus was not significant at 5 ppm Cr. The magnitude of the decrease due showing primary reactions for membrane damage leading to dysfunction to Cr addn. was much greater for content and uptake of Fe than of in respiration and osmoregulation. Mn. 104: 63739j Toxicology of selenium in a freshwater reservoir; 104; 63733c Ozone inhibits prostacyclin synthesis in pulmonary implications for environmental hazard evaluation and safety. endothelium. Friedman, Mitchell; Madden, Michael C.; Saunders, Lemly, A Dennis (Dep. Biol., Wake Forest Univ., Winston-Salem, D. Stephen; Gammon, Kenneth; White, Gilbert C., II; Kwock, NC 27109 USA). Eeotoxieol. Environ. Saf. 1985, 10(3), 314-33 Lester (Sch. Med., Univ. North Carolina, Chapel Hill, NC 27514 (Eng). A study was conducted to document patterns of accumulation USA). Prostaglandins 1985, 30(6), 1069-83 (Eng). The effects of of toxicity of Se to organisms in a power plant cooling reservoir in O3 on lung arachidonate [506-32-1] rnetab. in vitro were studied in North Carolina. Se entered the reservoir by way of effluent from the cultured bovine pulmonary endothelial cells exposed for 2 h to Oj in coal ash disposal basin, which contained 100-200 pg Se/L. Cor.cns. concns. <1.0 ppm. A concn.-dcpendent decrease in prostacyclin of Se in the lake water avs 10 pg/L, but were accumulated from 519 [35121-78-9] synthesis was found (907s decrease at the highest Oj times (periphyton) to 3975 times (visceral tissue, largemoutb has;) in level of 1.0 ppm). The inhibition of prostacyclin synthesis was not the biota. The pattern and degree of accumulation was essentially due to a decreased release of aruchidonic add from membrane lipids. complete within 2 yi after the initial operation of the power plant, The hypoxic pulmonary vasoconstrictive response to 10% O inhalation and persisted throughout the remainder of the study- fi.mes > insects in anesthetized dogs was studied in vivo after exposure to 1.0 ppm O3 > annelids > mollusks > crustaceans > plankton > periphyton. The for 1 h. Pulmonary vascular resistance was increased after Or planktonic and detrita) food pathways exposed fishes to potential exposure, similar to the findings in do^s given indomethacin (15 dietary concns. of Se that were some 770 and 519-1395 times the mg/kg). The percentage change in the hypoxic pulmonary pressor waterborne exposure, resp. Of the 0 species of fish originally response was similar between the O3 exposure and indomethacin-treated present in the reservoir, 16 were entirely eliminated, 2 were rendered groups, although due to the variance of the pulmonary vascular sterile but persisted as adults, 1 was eliminated but managed to resistance values during hypoxia the results did not reach statistical recolonize from a relatively ur.contaminaied headwater area as sterile significance. Evidently, Or inhalation affects pulmonary endothelial adults, and 1 was unaffected. Two nonnative fish species were arachidonate rnetab. in vivo as well as in vitro. accidentally introduced and established reproducing populations. 104; 63731d Effect of some heavy metals (copper, lead, zinc, Abundance and diversity of biota other than fishes was not affected. cadmium) on bacteria, protozoa, and algae. Terzieva, S ; Danon, Relative to control habitats, the contaminated reservoir had concns. S.; Dechcva, R.; Toncheva-Panova, T. (Inst Khim. Prof. Zabot., of waterborne Se that were 20-30 times background levels; the flora MA, 1431 Sofia, Bulg,). Khidrobiologiya 1985, 25, 30-41 (Bulg). and fauna contained about 10-15 times background. Thus, Se can The toxicity of Cu, Zn, Pb, and Cd (alone or in combination) to accumulate and be biol- magnified to toxic levels in a reservoir even bacteria (e.g., Escherichia coli, Streptococcus faecahs, Clostridium though waterborne concns. are in the low microgram/L range. This perfringens, or Salmonella typhimurium), algae (e.g,, Scrnedesmus study also provides date which indicate that current toxicol. acutus), and protozoa (e.g., Glaucoma chattoni, Uronemc marinum, information is neither accurate when used to predict the relative Tetrahymena pyriformis, Colpidium campylum, or Chilomonas sensitivity of individual fish species to Se, nor is it sufficient to paramecium) was studied. The effects of heavy metal pollution on predict community responses in a natural setting. It is very likely aquatic microorganism diversity and the biodegtdn. of org pollutants that long-term elevation of waterborne Se to 8-10 pg/L in warm-water is discussed. lakes and reservoirs would result in biotic responses similar to those 104: 63735e Lead and arsenic effects on pyruvate dehydrogenase documented in this report. activity in rat brain. Anca, Zoe; Gabor, Silvia (Inst. Ig Sanat 104- 63710c Adenylate cyclase and alkaline phosphatase activity Publics, Cluj Nnpoca, Rom.). Stud. Cercet. Biochim 19S5, 28(2), in the cerebral blood vessels of the rat in manganese chloride 125-9 (Rom). Pb and As al 0 2, 0.5, and 1.0 pM/50 mg wet tissue poisoning, Szumanska, Grazyna; Mossakowski, Mirosiaw J. (Cent. inhibited pyruvate dehydrogenase (I) [9014-20-4] activity in rat Med. Dos. Klin , PAN, Warsaw, Pol.). Nvuropatol. Pal. 1985, 23(3), brain in vitro. Th" inhibition was dose dependent. No additive 297-314 (Pol). In rats with Mn encephalopathy [induced by i.v. effects on I activity were noted when Pb and As were administered injection of 0.25 g Mn/kg (as MnClj) during 4 wk in 7 doses), the simultaneously. The I activity may reflect the interaction of Pb and activities of adenylate cyclase [9012-42-4] and alh. phosphatase As with the cholinergic system and with the energizing activity of the [9001-78-9] of cerebral capillary blood vessels were below normal. brain. The activity of alk. phosphatase remained low throughout the expt. 104; 63736f Effect of vinyl chloride on testis in rats, Bi, whereas the activity of adenylate cyclase returned to near normal at Wenfang; Wang, Youshen; Kuang, Meiyuang; Mcng, Deshan (Inst. the end of the expt. Health, China Natl. Cent. Prevent. Med., Beijing, Peop. Rep. China). 104: G3741d Mechanisms of aerosol deposition in a nasal Eeotoxieol Environ. Saf. 1985, 10(3), 281 -9 (Eng). Male rats (75) model, ltoh, H.; Smaldone, G. C.; Swift, D. L,; Wagner, H. N., Jr. inhaWcTTO. 100"or 300ti ppm vinyl chloride (VC) [75-01-4] 6 h/day (Dep. Nucl. Med., Kyoto Univ. Hosp,, Kyoto, Japan 606) J. Aerosol and 6 days/wk. In the 3rd, 0th, and 12th month following exposure Sci 1985, 16(6). 529-34 (Eng). Total and regional aerosol 8-30 rats of each group were killed. The others were under deposition were investigated in a model of a norma! tmman nasal observation and sacrificed after 18 mo. After exposure to VC. the airway. Contributions of fluid turbulence and parties inertia were organ and body wt. ratio, such as the kidney, liver, spleen, and heart evaluated using monodisperse aerosols. At fixed turbulent flow were increased, but those of the testis were decreased in the exptl. conditions, the deposition percentage increased with particle size >1 groups in the 6th month. The differences between exptl. groups and pm, suggesting that turbulent inertial deposition i; a primary the control group were statistically significant. The wts. of te-tis mechanism. With the same size aerosol, deposition increased with were decreased and damage of testicular seminiferous tubules was increasing fluid turbulence but its contribution was less with a larger found in rats by histopatbol. examrt. Incidence of damage of size aerosol Turbulent diffusion was the dominant transport testicular seminiferous tubules ir. the control, 10-, 100-, end mechanism for particles <1 pm, where deposition decreased with 3000-p_pm groups was 18.9, 29.7, 36.5, and 56.0%j, re;p. There was particle size. Two major deposition sites were visualized with an obvious dose-response relation between the concn of VC and the radioaerosul in the anterior ngion of the nasal airway. One is dose ASI 00004757