Document dxdpQzLem9Myjd5g707JjpOG

1231 ChimicMl Abstracts ' Vol. 66, 19-.7 -4 * 111 activity. C. V. Martiny- . Biol. Zh. nenii 19(8), 36--41 (1066)(Armcniart). In previous studies it was established that thedccompn. of proteins is accelerated by poisoning with chloro- prene. This process can be interrupted and the protein con tained in cells rapidly restored with hyposulfite soln. by an un known mechanism. Studies made to elucidate the influence of chloroprenc and hyposulfite on cathcpsin enzymes were incon clusive, and it is suggested that the most important factor in this modification is related to the transaminases. Expts. were con ducted using normal rats (control) and rats poisoned with chloro- prene (8 mg./l.. 2 hcs. daily, 2-3 months). The activities of glutamic-oxalacctic transaminase and glutamic-pyruvic trans aminase were measured by using the Reitman and Frankel method (CVt 51, 18080*) and arc expressed in Vroblcvski units. The activities of the cr.zymes decreased 10-19% in blood, liver, and kidneys and 41-51% in the spleen of poisoned animals. In in vitro expts. the decrease in enzyme activity in normal tissues was4.7-8.4% and in poisoned animals 2.3-7.1%; in the spleen the decrease was 0.4-0.5%. Hyposulfite also lowers the enzymic ac tivity; however, the combination, hyposulfite-chloroprenc re stores it to the initial level and in some cases even a higher level is reached. Chloroprenc does not affect the activity of pyndoxal phosphate. These results lead to the assumption that the in hibitory action of chloroprenc can be explained by its reaction with the protein part of the enzyme. L. B. Bcdighian 1231c Changes in the ester-.fied fatty acids and cholesterol in erum and liver of rats after application of orotic acid and hepato- toxic substances. F. Musil and J. Sueva (Skoda-Werke-Krank- enhauses, Plzen, Czech). Fette Seifert Anstnchm. 68(9), 748-50 (1966)(Gc.L Changes in the serum and hepatic levels of choles terol and cstcrificd fatty acids following oral administration of CC1, (0.5 ml./kg.) for the iiitrapcritoncal administration of ethio- nine (250 nig./kg.) to rats were in some cases normalized follow ing oral administrauon of orotic acid (100-250 mg./kg.) given as either a preventive or as a therapeutic agent. CMJG 1232k Acute (mouse and rat) and short-term (rat) toxicity studies on dibutyhdiethylene glycol bisphthalate). D. E. Hall, Patricia Austi i, and F. A. Fairweather (British Ind. Biot, Res. Assoc., Carsuaiton, Engl.). Food Cosmtl. Toxicol. 4(4), 383-8(1066)(Eng). Acute and short-term feeding studies have been carried out on a sample contg. 80% dibutyl (diethylene gly col bisphthalate) (DDGB). The intrapcritoneal L.D.w in both mice and rats wa_- , pprox. 11.2 g./kg. This dose when given orally was tolerated by both species without ill effect. The toxicity by either route in mice was enhanced when DDGB was administered in arach's oil (50% vol./vol.). In a 90-day study in rats given dietary levels of 0.0 (control), 0.25, 1.0. and 2.5% DDGB, significant growth retardation occurred in both sexes at all levels apart from males on 0.25%. This effect was attribut able, at least in part, to reduced food intake, although this effect was less marked in females. There were no hematological changes or effects on kidney function. At the 1.0 and 2.5% diet ary levels, the relative liver and heart wts. in males and the rela tive brain wts. in both sexes were significantly increased. No pathol. changes were found that could be attributed to DDGB. In view of the effect on growth at the lowest dietary level of 0.25%, a no-effect level in the diet of rats for 90 days could not be established for the particular batch of DDGB tested, RCTT 1233t Reaction of hydroxocobalamin with thiols. Norman Adler, Thomas Medwick, and T. J. Poznanski (Merck Chem. Div., Merck & Co., Inc.. Rahway, N.J.). J. Am. Chem. Soc. 88(21), 501S-20(19G6)(Eng). Hydroxocobalamin reacts with thiol compds., as exemplified by glutathione, to (orm relatively weak 1:1 inner coordination complexes. Previously reported in consistencies in the generality of this reaction are explained in terms of the simultaneous role of thiol compds. as complcxmg and reducing agents. RCJC 1234a Neurotoxic effects induced by alkylating agents. M. G. Donelli, R. Rosso, and S. Garattini. J. I'harm. Pharma col. 18(11), 7GO-2(1900)(Enir). In decreasing order of effective ness, DL-tryptophan mustard, O-sarcolysine, glycine mustard, L- sarcolysine, DL-sarcolysmc, and alanine mustard produced a typical pattern of nrurotoxicity when administered mtraccre- brally to rats. The typical pattern of neurotoxicity included n latency time of about 30 Ml nun., followed by signs of central stimulation, incoordinate movements, and stereotype behavior, and ending witli clonic convulsions and occasional tome exten sions. Mannitol must,ud, telraiuine, eyelopbosplmmiile, ami chlorambucil were not ucumtuxiu when administered m doses of 100 y/rut. Intrapcritoneal administration of Na pltcnytuin (10U mg./kg.) was ineffective in preventing the murotoxic effects in duced by the alkylating agents, whereas Na pheunhurbitnne showed a clear protective effect. Cysteine and thiourea (l g./ kg,, intrnperitoneally) were also ineffective m preventing the neurotoxie i ITt ets. ' CMJN 1235h Effect of chronic nortriptyline pretreatment on the cute toxicity of various medicinal agents in rats. 1). It. Mi vers, D. O. Rallytick, ami R. C. Audi rsou ( Hi Lilly ,V Co., Greenfield,, Indiana). J. Pharm. Set. 55(11), 13I7~I8( 19t;ti)(Eiig). A method using rats that c e of value in predicting the effects of chronic treatment with ,.>ycllotlierapcuttcs on the acute toxic ity of other medicinal agents is described. Results obtained by this method show I that nortriptyline, like amitriptyline, cn- hanccd the toxicity of most cerebral depressants lit att additive manner. Both of the antidepressive compds. markedly potenti ated the toxicity of physostigmme and to a lessor degree pilocar pine. Ephcdrinc toxicity was significantly antagonized by thymolcptic pretreatment. The test failed to verify reports that the tricyclic antidepressives dangerously potentiate the toxicity of ale. or monoamine oxidase inhibitors. Results indicated that a variety of medicinal agents can be used in the nortriptyline treated patient without any problem of significant drug inter action. RCVG 1236r Chlorinated anilines and their sanitary-toxicological characteristics. G. D. Khamucv. Khim. Faktory Viteshn. Sredy i ikhCigien. Znachenie, Sb., Moscow 1965, 108-10(Russ). Monochloroanilinc is used in the production of insecticides and dyes. m-Monochloroanilinc (Iland p-monochloroamline (II)dis solve in HiO (5 g./l.), in which they cause an unpleasant taste and odor. The odor and taste perception thresholds were 2.6 and 7.2 for I and 1.5 and 3-6 mg./l. for II, resp. In a concn. of 150 mg./l., I and II lowered the B.O.D. of water. Threshold conens. are 1.5 mg./l. for I and 0.75 mg./l. for II. The L.D. values (stomach administration) for I and II. resp., were 1104 and 401 for white mice, 1104 and 368 for white rats, and 750 and 350 mg./kg. for guinea pigs. A 3-month sub-acute expt., conducted on white rats with stomach administration of 0.1 L.D.m levels, caused the formation of mcthcmoglobin and re duced the hemoglobin level and the erythrocyte count. From Ref. Zh., Khim. 1966(8), Pt. If, Abstr. So. 81414. MVRK i237y Toxicity of thioacetamide. Z. Hrubai, W. Gradman, A. Slesers, and M. Lubran (Univ. of Chicago). Cab. Invest. IS (11), 174S-60( 1966)(Eng). Thioacetamide (I), fed to rats in a diet contg. 50 mg./kg. body wt./day for 5 days, produced high scrum lactic dehydrogenase levels and centrolobular necrosis of the livers within 24 hrs.; the enzyme levels decreased and the necrotic areas were resorbed within 3 days of feeding the diet. Severe degenerative changes in the kidneys, hematuria, and in creased serum urea N and serum creatinine levels occurred within 48 hrs. of treatment. The lethal effects of the above level of I were correlated with the renal damage. Excess dietary casein hydrolyzate, methionine, or guanosine reduced the mortality and renal toxicity of I, although these compds. did not present the nuclear and nucleolar enlargement of hepatic cells and of the cells of the proximal convoluted tubules of the kidney occurring in treated rats. 67 references. BPJN I238f Poisoning by grass. C. H. Gallagher, J. H. Koch, and H. Hoffmann (Univ. Sydney). New Scientist 31(510), 412-- 14(1966)(Eng). Acute and chronic neuromuscular disorders occur in sheep feeding on the pasture grass Phalaris tuberosa. This grass contained 0.3% (dry wt.) tryptamine alkaloids. Tissues from sheep undergoing acute poisoning showed no histol. alterations, whereas the brain and kidneys of chronically poisoned animals showed deposits of green pigment. The pigment was noted in the mitochondria cells of the mid-brain, brain stem, and spinal cord. It is suggested that these changes are related to the oxidative deamination of N.jV-dimcthyltryptamine and 5-mc- thoxy-N,.V-dimcthyItryptamine. The protective action of Co against the chronic form of the disease, reported by others, may be related to the prevention of degenerative changes in nerve tissue or to the acceleration of alkaloid metabolism. W. L. Downs 1239p Vinyl chloride; industrial toxicologic aspects. I. Grigorcscu and Gh. Ttfca, Rev. Chim. (Bucharest) 17(8), 499- 501(1966)(Rom). A hypothesis was put forward, claiming that CH:CHC! (I) could react with H-O at the level of the hepatic cell, yielding ethylene ttionochlorohydrin, which could be oxi dized to chloral and chloroacetic acid (II). II could be elimi nated as such in the urine or he metabolized further through ami- nation to glycocol. An anal, method was developed for detec tion of II in urine, assuming that the only other source of II could be massive ingestion of wine yeast or inhalation of trichloro ethylene. An aliquot (200 cc.) of urine, acidified with 50'r H:S04 (2 cc.) is extd. with Et:0 (200 cc.), shaking vigorously, anil settling for 24 hrs. The Cxt. is dried (unltyd. Na;SO,h evnpd. to dryness under reduced pressure, and the residue is dis solved in 50%, uq. ulc. soln. (0.5 cc.). One drop of the >.,1111. (25- 30 mE) is placed on Whatman No. I paper strips (2.'> n 3 cm.), dried, unit chromatographed by ascending method, using us clutaut the tuixt. Nil,Oil-KtOll I lit) (l.k'0 4) for a period of 0 hrs. The strips, driixl in air, are kept 24 hrs. in a coned. Nllj atm., heated for 5 min. at 80, sprayed with 0.1' . ninhydrin in MeOIl, and driixl. Tlu II is indicated by reddi'h- violet spots. For distinct development, the strips are spuiol finally with 10'CidNOjb (carmine red spots). The K, at -'I was established with a sola, n! 2D-30 pg. II/cc., as O.SO. 1 h, limit of sensitivity is It. I ^g. II, ami is improved by tile use of Gu (NO,),, The extn. of II from urine was demonstratixl by treat ing a soln. of 25 pg. II/cc. in urine as almve, cutting the cons* BOR 009705