Dokov, V.

Georgieva, P.

Konstantinova, R.

Michailova, E.

Tzonevski, D.

Vasileva, M.

Vladov, V.

English

Varna Medical University Press: Journals

STUDY OF T H E ACUTE TOXICITY AND COMBINED ACTION OF T H E PESTICIDES A C R E X AND A C T E L I C D. Tzonevski, V. Dokov, E . Michailova, P. Georgieva, M. Vasileva, R. Konstantinova, V. Vladov Key-words: acute toxicity — pesticides — acrex — actelic Material and methods Acrex (isopropyl-2-1 methyrn-propyl-4,6-dinitrophenyl-carbonate) is a contact acaracide and fungicide from the group of the nitroderivatives of phenol. The base mechanism of action upon the insects and vertebrates is connected directly wi th disorders in the processes of oxidative phosphorilation. Actel ic (2-diethylamino-6-methylpyrimidine-4-il-dimethyl-phosphate) is an in-secticide and acaracide wi th a broad spectrum of action. The main mechanism of its toxic act iv i ty is the inhibit ion of some esterases. The experiments were carried out wi th 220 white rats, weighing 150—200 g, female and male, divided into two groups (experimental and control). The stu-died agents were given per os by means of a stomach d r i l l . We applied a techni-cal acrex (30 % active reagent) and technical actelic (50 % active reagent). The actual experiment itself wi th the combined acrex and actelic was held on 150 white rats, divided into groups of 6 animals each. The average lethal dose ( L D 5 0 ) of the acrex was determined by treating of the experimental animals wi th 25, 50, 100, 200, 250 mg/kg, whereas the actelic was respectively 500, 700, 11000, 1250, 1500, 1750, 2000 mg/kg; the rats were examined after that for a period of 14 days. As for the determination of the L D 5 0 of the combination of acrex and actelic we used equitoxic doses of both compounds: 0.2, 0.3, 0.7, 1.0, 1.5 L D 5 0 which a l l were applied consequently following an internal of maximum several seconds. The acute oral, mean lethal doses of the active substances and the combina-tion of them were estimated after Leenfield Wil lcoxon (9). The type of the combi-ned action was determined by using the method of F inney and the method of Kagan (2,9). The histological changes in parenchyma organs as a result of the application of the combination acrex and actelic were studied over a total of 70 rats, divided into 3 experimental groups and another one control. The experimental animals were treated as follows: I group — 1/2 L D 5 0 acrex (71 mg/kg), I I group — 1/2 L D 5 0 actelic (625 mg/kg), I I I group — 1/2 L D 5 0 mixture (400 mg/kg). The experimental animals were decapitated on the first, fourth and fif-teenth day after a single-dose-application. After that histological preparations from their internal organs were prepared ( l iver , heart, spleen, kidney, stomach). 3 Scpipta scientifica medica • > 34 D. Tzonevski, V . Dokov, F . Michailova. Results and discussion The development of the acute intoxication and the results of lethality were investigated in dynamics — 14 days after a single-dose-application. Table 1 shows the results of the experiment: the preparation acrex (nitrophenol) is one of the T a b l e 1 Levels of oral doses L D 5 l ) in mg/kg for white rats Preparation L D i e L D ' s o Confidential interval L D 8 4 Acrex Actelic ' Double mixture (acrex and actelic) 53,0 720.0 280,0 142,0 1250,0 800 0 71—284,0 Ю87—14З7 615—1040,0 380,0 2400,0 2300,0 highly toxic compounds wi th L D 5 0 1 42 mg/kg, whereas actelic is one cf the sl ight ' ly toxic ones wi th L D 5 0 1250 mg/kg; their mixture is an averagely toxic prepa­ration wi th L D 5 0 800 mg/kg. The quantitative evaluation of the combined effect of the pesticides acrex and actelic, held after F inney and Kagan was 115 % (88—145 % ) and 1.18=0.32. The ratio between the expected L D 5 0 and the experimental L D 5 0 , specially after the combined treatment and additive effect, according to the methods of Finney and Kagan was equal to 1.0. Hav ing in mind the individual va r i ab i l i ty the au­thors suggested al l ratios under 0.57 to be directed as antagonism and above 1.75 as synergism ( 1 , 2, 8) . According to our data the expected L D 5 0 is 696 mg/kg and the experimental one — 800 mg/kg. Rat io 0.87 shows already a tendency of antagonism after ad­dit ive action. I t is known that pesticides from the group of dinitrophenols and Р О С can be metabolised in the l iver , which is the first barrier after a stomach application. There are enough bibliographical data that the acrex is an inducer of oxidases wi th combined functions (7). The simultaneous application of acrex and actelic decreases the inhibi t ing cholinesterase action of the actelic as a result of the activated l iver metabolism of the latter (9). Th i s is a direct result of the acute intoxicative effect of the combination, as wel l as it can be established by studying the histological disorders in the parenchyma organs. When the acute intoxicat in of the preparations is wi th high doses of the rea­gents (absolute lethal dose L D 1 0 0 ) , we register a decreased mobility of the trea­ted wi th acrex animals, higher frequency of breathing and pulse, a taxia , relea­sed evacuation of reservoirs, febri l i ty . The acute intoxication wi th actelic can be demonstrated 65 minutes after the oral application and is characterized by increased irr i tat ion, a taxia , strong atonia, even paresis of the rear extremities, sal ivat ion, frequent breathing, tremor and pulsations. The animals die in teta­nic spasm. The acute intoxication after the combined action of both reagents is manifested about 75—80 minutes after the oral application and the syndrome here is slightly weaker (muscarin-like), also there are no tetanic spasms. After decapitation of the treated rats wi th L D 5 0 of both reagents and their mixture in the parenchyma organs cf the a r i r ra l s can be seen macroscopic haemor-Study of the acute toxicity and. 35 rhages and oedema. The histological analysis of the organs after treatment wi th acrex shows cyanosis and slight parenchyma distrophy. After actelic treatment the tissue changes are quite heavier: parenchyma, even vacuolar distrophy prevail­ing in the hepatocytes. I n the parenchyma of the lungs can be registered larger haemorrhages than those after acrex treatment. Most weakly expressed chan­ges are established after a combined treatment wi th both reagents together. More demonstrative are those disorders in the organs of the animals after 4 days. I n the l iver , for example, for a l l three types of intoxication we found a vacuolar-spotted distrophy of the hepatocytes, vessels' di latat ion, erythrostasis, some­where wi th plasmorrhagia. I n the myocard can be seen erythrostasis, vessels' dila­tation, parenchyma microhaemorrhages, distrophic changes and zones fragmen­tation of cardiomyocytes. I n the kidneys we registered vessels' di atation and erythrostasis. Most serious are the lung disorders: large parenchyma haemorrhages, ves­sels' dilatation and actelectasis wi th stightly expressed oedema (in the rats trea­ted separately wi th the reagents). Weaker were the changes in the animals trea­ted wi th the combined mixture: only parenchyma microhaemorrhages. Conclusions 1. The combined effect of the preparations acrex and actelic is demonstra­ted by the type of additive action wi th a tendency towards antagonism. 2. The weaker toxic ac t iv i ty of the combination upon experimental animals and its relat ively well expressed insecticidic and acaracidic properties allows the simultaneous application of acrex and actelic in the agriculture. R E F E R E N C E S 1. Б а й н о В а, А. Хигиенна токсикология. С , Медицина и физкултура, 1981. 112 с. — 2. К а г а н , Ю. С. Гиг. и санит., 1973, 12, 890. — 3. О с е т р о в , В. В. В: Ги­гиена, токсикология новых пестицидов и клиника отравлений. Киев, 1962, 396—401. — 4. С в е т л ы й , С. С. В: Основные подходы и актуальные вопросы применения пестици­дов в различных климато-географических зонах. Ереван, 1976, 89—92. — 5. Ц о н е в -с к и, Д . Лет. ХЕС, 1979, 8, 53—59. — 6. Ц о н е в с к и, Д . Канд. дис. С , 1974. — 7. Я к у ш к о, В. , З . З л а т е в . Гиг. труда и проф. забол., 1975, 9, 55—57. — 8. D u ­b o i s , К . P . Canad. Med. Assoc. J . , 100, 1969, 173. — 9. F i n n e y , D. Probe analysis. A statistical treatment of the sigmoid response curve. London, Cambridge Univ . Press, 2 ed.1952. ИССЛЕДОВАНИЕ ОСТРОЙ ТОКСИЧНОСТИ И КОМБИНИРОВАННОГО ДЕЙСТВИЯ ПЕСТИЦИДНЫХ АКРЕКС И АКТЕЛИК Д . Цоневски, В. Доков, Е . Михайлова, П. Георгиева, М. Василева, Р. Константинова, В. В ладов Р Е З Ю М Е Авторы изучают острую токсичность, симптомы отравления и морфологические изме­нения внутренних органов белых крыс, которым вводились пестицидные препараты — акрекс (30 % ) , актелик (50 % ) и двойная смесь обоих веществ. Зб D. Tzonevski, V . Donkov, Е. Michailova.. . Устанавливается, что препарат акрекс принадлежит у высокотоксичным веществам, соответствено с ЛД 5 0 -142 мг/кг, а препарат актелик относится к слабо токсичным пестици­дам — с ЛД 5 0 -800 мг/кг. Комбинированный эффект обоих веществ проявляется по типу адитивного действия, установленого методом Фини — 115 % (88 % —145 % ) и методом Ю. С. Каган — 1,18—0,32 с тенденцией к антагонизму. При анализе морфологических изменений паренхиматозных органов животных, которым вводились препараты, устанавливаются значительные дистро­фические, некротические и воспалительные увреждания, что отмечалось преимущественно при введении препаратов в дозах 1/2 Л Д 5 0 . В результате проведенного исследования авторами рекомендуется применение двой­ной смеси препаратов акрекс и актелик в оранжерийных условиях. 

STUDY OF THE ACUTE TOXICITY AND COMBINED ACTION OF THE PESTICIDES ACREX AND ACTELIC

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STUDY OF THE ACUTE TOXICITY AND COMBINED ACTION OF THE PESTICIDES ACREX AND ACTELIC

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