ó㳺í³÷íà ðåãëàìåíòàö³ÿ ³êàðèäèíó â ïîâ³òð³ ðîáî÷î¿ çîíè

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ó㳺í³÷íà ðåãëàìåíòàö³ÿ ³êàðèäèíó â ïîâ³òð³ ðîáî÷î¿ çîíè

Êóçüì³íîâ Á.Ï., Çàçóëÿê Ò.Ñ., Òóðê³íà Â.À., Êóçüì³íîâ Î.Á., Ëüâ³âñüêèé íàö³îíàëüíèé ìåäè÷íèé óí³âåðñèòåò ³ìåí³ Äàíèëà Ãàëèöüêîãî

Ìåòà, Îá´ðóíòóâàííÿ ã³ã³ºí³÷íîãî ðåãëàìåíòó äîïóñòèìîãî âì³ñòó ðåïåëåíòó ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè.

Îá'ºêò ³ ìåòîäè äîñë³äæåííÿ. ³êàðèäèí (1-(1-ìåòèëïðîïîêñèêàðáîí³ë)-2-(2- ã³äðîêñ³åòèë)ï³ïåðèäèí), âèðîáíèöòâà ô³ðìè S.C. Johnson Europlant B.V. (ͳäåðëàíäè). Ìåòîäè äîñë³äæåíü - òîêñèêîëîãî-ã³ã³ºí³÷í³, á³îõ³ì³÷í³, ³ìóíîëîã³÷í³, ô³çèêî-õ³ì³÷í³, ñòàòèñòè÷í³.

Ðåçóëüòàòè äîñë³äæåííÿ òà ¿õ îáãîâîðåííÿ. Ïðåäñòàâëåí³ ðåçóëüòàòè òîêñèêîëîãî-ã³ã³ºí³÷íèõ äîñë³äæåíü ðåïåëåíòó ³êàðèäèíó íà ëàáîðàòîðíèõ òâàðèíàõ (á³ë³ ìèø³, á³ë³ ùóð³, ìóð÷àêè, êðîë³). Âñòàíîâëåíî, ùî ³êàðèäèí çà ïàðàìåòðàìè ãîñòðî¿ òîêñè÷íîñò³ ïðè îäíîðàçîâîìó âíóòð³øíüîøëóíêîâîìó ââåäåíí³ òà îäíîêðàòíîìó ³íãàëÿö³éíîìó âïëèâîâ³ â³äíîñèòüñÿ äî ïîì³ðíî íåáåçïå÷íèõ ðå÷îâèí (3 êëàñ íåáåçïåêè. Âèäîâà ÷óòëèâ³ñòü òâàðèí äî ðå÷îâèíè â³äñóòíÿ. Ïðè íàíåñåíí³ íà øê³ðó ³êàðèäèí íå âèêëèêຠçàãèáåë³ òâàðèí òà ïðîÿâ³â ì³ñöå-ïîäðàçíþâàëüíî¿ ä³¿. Âïëèâ íà ñëèçîâ³ îáîëîíêè õàðàêòåðèçóºòüñÿ íåçíà÷íîþ ïîøêîäæóþ÷îþ 䳺þ (2 áàëè).

 ñóáõðîí³÷íîìó åêñïåðèìåíò³ ïðîÿâëÿº ñëàáêó êóìóëÿòèâíó àêòèâí³ñòü. Õðîí³÷íèé ³íãàëÿö³éíèé âïëèâ ³êàðèäèíó óïðîäîâæ 4 ì³ñÿö³â íå âèêëèêຠçì³í ãåìàòîëîã³÷íèõ ³ á³îõ³ì³÷íèõ ïîêàçíèê³â, ïàòîëî㳿 ðåñï³ðàòîðíèõ øëÿõ³â òà ïàðåíõ³ìàòîçíèõ îðãàí³â. ²êàðèäèí âîëî䳺 ñåíñèá³ë³çóþ÷îþ àêòèâí³ñòþ ³ âèêëèêຠçðîñòàííÿ ê³ëüêîñò³ öèðêóëþþ÷èõ ó êðîâ³ ³ìóííèõ êîìïëåêñ³â. Íå ÷èíèòü òîêñè÷íîãî âïëèâó íà ðåïðîäóêòèâíó ôóíêö³þ. Áåçïå÷íèé â ïëàí³ ðîçâèòêó êàíöåðîãåííîãî åôåêòó. Íà ï³äñòàâ³ âñòàíîâëåíèõ ïàðàìåòð³â òîêñè÷íîñò³ ðîçðàõîâàíî êîåô³ö³ºíò çàïàñó, çàïðîïîíîâàíî ã³ã³ºí³÷íèé ðåãëàìåíò äîïóñòèìîãî âì³ñòó ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè òà ðîçðîáëåíî ìåòîäèêó âèì³ðþâàííÿ ìàñîâî¿ êîíöåíòðàö³¿ ðå÷îâèíè ó ïîâ³òð³.

Âèñíîâêè. Ãðàíè÷íî äîïóñòèìà êîíöåíòðàö³ÿ ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè ðåêîìåíäóºòüñÿ íà ð³âí³ 10 ìã/ì³, ïàðè + àåðîçîëü, 3 êëàñ íåáåçïåêè. Ðîçðîáëåíî ãàçîõðîìàòîãðàô³÷íó ìåòîäèêó âèì³ðþâàííÿ ìàñîâî¿ êîíöåíòðàö³¿ ³êàðèäèíó ó ïîâ³òð³.

Êëþ÷îâ³ ñëîâà. ²êàðèäèí, ïàðàìåòðè òîêñè÷íîñò³, ãðàíè÷íî äîïóñòèìà êîíöåíòðàö³ÿ, ïîâ³òðÿ ðîáî÷î¿ çîíè.

Hygienic regulation of icaridin in the air of the working area

B.P. Kuzminov, T.S. Zazulyak, V.A. Turkina, O.B. Kuzminov, Danylo Halytsky Lviv National Medical University

Objective. Substantiation of the hygienic regulations for the permissible content of the repellent icaridin in the air of the working area.

Materials and methods. Icaridin (1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine), manufactured by S.C. Johnson Europlant B.V. (The Netherlands) Research methods are the following: toxicological-hygienic, biochemical, immunological, physicochemical, statistical.

Results. The results of toxicological and hygienic studies of the repellent icaridin on laboratory animals (white mice, white rats, guinea pigs, rabbits) are presented. It has been established that icaridin, in terms of acute toxicity with a single intragastric administration and a single inhalation exposure, belongs to moderately hazardous substances (hazard class 3). Species sensitivity of animals to the substance is absent. When applied to the skin, icaridin does not cause death of animals and manifestations of an irritant effect. The impact on the mucous membranes is characterized by a slight (minor) damaging effect (2 points). In the subchronic experiment, it shows a weak cumulative activity.

Chronic inhalation effect of icaridine for 4 months does not cause changes in hematological and biochemical parameters, pathology of the respiratory tract and parenchymal organs. Icaridin has sensitizing activity and causes an increase in the number of immune complexes circulating in the blood. It does not have a toxic effect on reproductive function and is safe in terms of the development of a carcinogenic effect. Based on the established toxicity parameters, a safety factor was calculated, a hygienic regulation for the permissible content of icaridin in the air of the working area was proposed, and a method for measuring the mass concentration of a substance in the air was developed.

Conclusions. The maximum allowable concentration of icaridin in the air of the working area is recommended at the level of 10 mg/m³, vapors + aerosol, hazard class 3. A gas chromatographic technique for measuring the mass concentration of icaridin in air has been developed.

Keywords. Icaridin, toxicity parameters, maximum allowable concentration, control of the working area.

Âñòóï

²êàðèäèí (1-(1-ìåòèëïðîïîêñèêàðáîí³ë)-2-(2-ã³äðîêñ³åòèë)ï³ïåðèäèí) - öèêë³÷íèé àì³í, ïîõ³äíå ï³ïåðèäèíó, áóâ ñèíòåçîâàíèé êîìïàí³ºþ Bayer ó 1980-õ ðîêàõ íà îñíîâ³ ìîëåêóëÿðíîãî ìîäåëþâàííÿ òà ïðèçíà÷åíèé äëÿ â³äëÿêóâàííÿ êîìàõ, òàêèõ ÿê êîìàð³, ìóõè, êë³ù³ òà áëîõè, øëÿõîì ì³ñöåâîãî çàñòîñóâàííÿ àáî ïîâåðõ îäÿãó. ²êàðèäèí îô³ö³éíî ë³öåíçîâàíèé äëÿ âèêîðèñòàííÿ â ÑØÀ ó 2001 ðîö³ òà â Êàíàä³ ó 2012 ðîö³. Êàíàäñüêèé êîíñóëüòàòèâíèé êîì³òåò ç òðîï³÷íî¿ ìåäèöèíè òà ïîäîðîæåé Àãåíòñòâà îõîðîíè çäîðîâ'ÿ Êàíàäè ââàæຠéîãî ðåïåëåíòîì ïåðøîãî âèáîðó äëÿ ìàíäð³âíèê³â â³êîì â³ä øåñòè ì³ñÿö³â äî 12 ðîê³â. Ïîâ³äîìëÿºòüñÿ, ùî ñòóï³íü ïîäðàçíþâàëüíî¿ ä³¿ ³êàðèäèíó ìåíøå í³æ ä³åòèëòîëóàì³äó - ùå îäíîãî ïîøèðåíîãî ðåïåëåíòó â³ä êîìàõ, ³ ïðîäóêòè, ùî ì³ñòÿòü äî 20% ³êàðèäèíó, ââàæàþòüñÿ áåçïå÷íèìè äëÿ òðèâàëîãî çàñòîñóâàííÿ ó äîðîñëèõ [1].

 Óêðà¿í³ ðîçïî÷àòî âèïóñê «Raid ïëàñòèíè â³ä ìóõ äëÿ åëåêòðîôóì³ãàòîðà» ç âèêîðèñòàííÿì ³êàðèäèíó, âèðîáíèöòâà ô³ðìè S.C. Johnson Europlant B.V. (ͳäåðëàíäè), ùî îáóìîâëþº íåîáõ³äí³ñòü çä³éñíåííÿ êîíòðîëþ çà áåçïå÷íèì âì³ñòîì ñïîëóêè ó ïîâ³òð³ ðîáî÷î¿ çîíè âèðîáíè÷èõ ïðèì³ùåíü.

Ìåòà ðîáîòè. Îá´ðóíòóâàííÿ ã³ã³ºí³÷íîãî ðåãëàìåíòó äîïóñòèìîãî âì³ñòó ðåïåëåíòó ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè.

Îá'ºêò ³ ìåòîäè äîñë³äæåíü

Îá'ºêòîì äîñë³äæåííÿ áóâ ðåïåëåíò ³êàðèäèí. Õ³ì³÷íà íàçâà 1-(1-ìåòèëïðîïîêñèêàðáîí³ë)-2-(2-ã³äðîêñ³åòèë)ï³ïåðèäèí. Ðåºñòðàö³éíèé íîìåð çà CAS: 119515-38-7. Åìï³ðè÷íàôîðìóëà: Ñ12Í23ÍÎ3.

Ñòðóêòóðíà ôîðìóëà:

Çà àãðåãàòíèì ñòàíîì ³êàðèäèí - ð³äèíà, áåç çàïàõó, â³ä áåçáàðâíîãî äî ñâ³òëî-æîâòîãî êîëüîðó. Ñòóï³íü ÷èñòîòè ðå÷îâèíè ñòàíîâèòü 98,7%. Ãóñòèíà: 1,07 ã/ñì³ (ïðè 20°Ñ). ³äíîñíà ìîëåêóëÿðíà ìàñà 229,320. Òî÷êà êèï³ííÿ: 296°Ñ ïðè 760 ìì ðò. ñò. Òî÷êà ïëàâëåííÿ 170°Ñ. Òèñê ïàðè: 3,4*10^-4 ãÏà ïðè 20°Ñ; 5,9*10^-4 ãÏà ïðè 25°Ñ; 7,1 *10^-3 ãÏà ïðè 50°Ñ. Ðîç÷èíí³ñòü ó âîä³ (ã/100 ñì³) ïðè 20°Ñ - 0,82. Ðîç÷èíí³ñòü â àöåòîí³ - 752 ã/100 ñì³).

Äîñë³äæåííÿ ïðîâîäèëèñü íà ëàáîðàòîðíèõ òâàðèíàõ (á³ë³ ìèø³, á³ë³ ùóð³, ìóð÷àêè, êðîë³), ÿê³ óòðèìóâàëèñü â óìîâàõ â³âàð³þ Ëüâ³âñüêîãî íàö³îíàëüíîãî ìåäè÷íîãî óí³âåðñèòåòó ³ìåí³ Äàíèëà Ãàëèöüêîãî. Åêñïåðèìåíòàëüí³ òâàðèíè îòðèìóâàëè ñòàíäàðòíèé ãðàíóëüîâàíèé êîðì ç íåîáìåæåíèì äîñòóïîì äî ïèòíî¿ âîäè. ϳä ÷àñ ïðîâåäåííÿ äîñë³äæåíü íà òâàðèíàõ äîòðèìóâàëèñü ïðèíöèï³â á³îåòèêè, çàêîíîäàâ÷èõ íîðì òà âèìîã çã³äíî ç ïîëîæåííÿìè «ªâðîïåéñüêî¿ êîíâåíö³¿ ïðî çàõèñò õðåáåòíèõ òâàðèí, ùî âèêîðèñòîâóþòüñÿ äëÿ äîñë³äíèõ òà íàóêîâèõ ö³ëåé» [2] òà «Ïîðÿäêîì ïðîâåäåííÿ íàóêîâèìèóñòàíîâàìè äîñë³ä³â, åêñïåðèìåíò³â íàòâàðèíàõ» [3].

Ðåçóëüòàòè äîñë³äæåííÿ òà ¿õ îáãîâîðåííÿ

Âñòàíîâëåííÿ ïàðàìåòð³â òîêñè÷íîñò³ ïðè ïåðîðàëüíîìó íàäõîäæåíí³ ³êàðèäèíó çä³éñíþâàëîñü â ãîñòðîìó äîñë³ä³ íà 36 á³ëèõ ìèøàõ, ÿêèì ó øëóíîê çà äîïîìîãîþ çîíäà ââîäèëè ïðåïàðàò â äîçàõ 1000-4000 ìã/êã. Õàðàêòåð òîêñè÷íî¿ ä³¿ âèçíà÷àëè çà ïîêàçíèêîì âèæèâàííÿ, ïîâåä³íêîþ òâàðèí, ñïîæèâàííÿì ¿æ³ òà âîäè. Ñïîñòåðåæåííÿ çà òâàðèíàìè çä³éñíþâàëè óïðîäîâæ 14 ä³á.

Êë³í³÷í³ ïðîÿâè îòðóºííÿ õàðàêòåðèçóâàëèñü íåòðèâàëèì ïåð³îäîì çáóäæåííÿ, ÿêå çì³íþâàëîñü çíèæåííÿì ðóõîâî¿ àêòèâíîñò³ óïðîäîâæ 1-2 ãîäèí ï³ñëÿ ââåäåííÿ. Çàãèáåëü òâàðèí â³äáóâàëàñü óïðîäîâæ ïåðøî¿ äîáè. Ñåðåäíüîñìåðòåëüíà äîçà (DL₅q) ³êàðèäèíó ñòàíîâèòü 4700 ìã/êã, ùî â³äïîâ³äຠ3 êëàñó íåáåçïåêè - ðå÷îâèíè ïîì³ðíî òîêñè÷í³.

Îäíîêðàòíó ³íãàëÿö³éíó ä³þ ³êàðèäèíó âèâ÷àëè øëÿõîì ³íòðàíàçàëüíîãî ââåäåííÿ ïðåïàðàòó á³ëèì ùóðàì â ê³ëüêîñò³, ùî â³äïîâ³äàëà êîíöåíòðàö³ÿì 1000,0 ìã/ì³ ³ 2000,0 ìã/ì³. Ïðè öüîìó çàãèáåë³ òâàðèí íå çàô³êñîâàíî óïðîäîâæ âñüîãî ïåð³îäó ñïîñòåðåæåííÿ (14 ä³á). ϳñëÿ ââåäåííÿ ðå÷îâèíè ó á³ëèõ ùóð³â ñïîñòåð³ãàëîñü çá³ëüøåííÿ ðóõîâî¿ àêòèâíîñò³, ÿêå çì³íþâàëîñü àäèíà쳺þ. ×åðåç 30-60 õâèëèí ñòàí òâàðèí íîðìàë³çóâàâñÿ. Çàãèáåë³ òâàðèí óïðîäîâæ 14 äí³â ñïîñòåðåæåííÿ íå â³äì³÷åíî.

Çà äàíèìè ë³òåðàòóðè ñåðåäíüîñìåðòåëüíà êîíöåíòðàö³ÿ (CL50) ³êàðèäèíó äëÿ ñàìö³â ùóð³â ïåðåâèùóº 4364 ìã/ì³ [4]. Êîåô³ö³ºíò âèäîâî¿ ÷óòëèâîñò³ äîð³âíþº 2,1 ³ ñâ³ä÷èòü ïðî â³äñóòí³ñòü âèäîâî¿ ÷óòëèâîñò³ òâàðèí äî ðå÷îâèíè.

Ç ìåòîþ âèçíà÷åííÿ ïîðîãîâî¿ êîíöåíòðàö³¿ ³êàðèäèíó ïðè îäíîêðàòíîìó ³íãàëÿö³éíîìó âïëèâ³ (Limac) ðå÷îâèíó ââîäèëè ³íòðàíàçàëüíî á³ëèì ùóðàì â äîçàõ 2 ìã, 5 ìã ³ 15 ìã, ùî â³äïîâ³äàëî êîíöåíòðàö³ÿì 64 ìã/ì³, 160 ìã/ì³ òà 480 ìã/ì³.

ßê êðèòå𳿠òîêñè÷íîãî âïëèâó âèçíà÷àëè á³îõ³ì³÷í³ òà ãåìàòîëîã³÷í³ ïîêàçíèêè.

Çà ðåçóëüòàòàìè äîñë³äæåíü áóëî âñòàíîâëåíî, ùî îäíîêðàòíèé ³íãàëÿö³éíèé âïëèâ ³êàðèäèíó â óñ³õ äîñë³äæåíèõ êîíöåíòðàö³ÿõ íå âèêëèêàâ çàãèáåë³ ï³ääîñë³äíèõ òâàðèí. Êë³í³÷í³ ñèìïòîìè ³íòîêñèêàö³¿ õàðàêòåðèçóâàëèñÿ çíèæåííÿì ðóõîâî¿ àêòèâíîñò³ óïðîäîâæ 2-3 ãîäèí â³ä ïî÷àòêó åêñïåðèìåíòó.

ßê âåëè÷èíà Limac ³êàðèäèíó ïðè îäíîêðàòíîìó ³íãàëÿö³éíîìó âïëèâîâ³ ïðèéíÿòà êîíöåíòðàö³ÿ 160 ìã/ì³, ïðè 䳿 ÿêî¿ ó ï³ääîñë³äíèõ òâàðèí ÷åðåç 2 ãîäèíè ñïîñòåð³ãàëîñü ñòàòèñòè÷íå çá³ëüøåííÿ ïðîöåíòíîãî âì³ñòó åîçèíîô³ë³â, íåéòðîô³ë³â ³ ë³ìôîöèò³â òà çá³ëüøåííÿ ð³âí³â öèðêóëþþ÷èõ ³ìóííèõ êîìïëåêñ³â. Ðåøòà äîñë³äæóâàíèõ ïîêàçíèê³â ñóòòºâî íå â³äð³çíÿëèñü ó ïîð³âíÿíí³ ç êîíòðîëåì.

Çîíà ãîñòðî¿ ä³¿ ³êàðèäèíó ñòàíîâèòü 27 (3 êëàñ íåáåçïåêè).

Îäíîêðàòíå çàíóðþâàííÿ õâîñò³â á³ëèõ ìèøåé ó íàòèâíó ðå÷îâèíó âïðîäîâæ 2 ãîäèí íå âèêëèêàëî çàãèáåë³ òâàðèí òà ñèìïòîì³â ðåçîðáòèâíîãî åôåêòó. Âîäíî÷àñ çì³í íà øê³ð³ íå â³äì³÷åíî.

Âíåñåííÿ 50 ìã ³êàðèäèíó ó êîí'þíêòèâàëüíèé ì³øîê îêà êðîëÿ âèêëèêàëî íåçíà÷íó ïîøêîäæóþ÷ó ä³þ: 2 áàëè çà êëàñèô³êàö³ºþ A. Mayda ³ Ê. Chrusaielska (âèä³ëåííÿ - 1 áàë, íàáðÿê - 0 áàë³â, ã³ïåðåì³ÿ - 1 áàë). ³äíîâëåííÿ îôòàëüìîñòàòóñó ñïîñòåð³ãàëîñü íà 2 äîáó áåç ïðîâåäåííÿ ìåäèêàìåíòîçíîãî ë³êóâàííÿ.

Êóìóëÿòèâíó àêòèâí³ñòü ³êàðèäèíó âèçíà÷àëè â ñóáõðîí³÷íîìó åêñïåðèìåíò³ çà ìåòîäèêîþ ˳ìà ³ ñï³âàâòîð³â. Ðå÷îâèíó ââîäèëè ùîäåííî á³ëèì ùóðàì ó ïîñòóïîâî (÷åðåç êîæí³ 4 äí³) íàðîñòàþ÷èõ äîçàõ. Ïî÷àòêîâèé ð³âåíü âïëèâó ñòàíîâèâ 1/10 DL50. Êë³í³÷íà êàðòèíà ³íòîêñèêàö³¿ ðîçâèâàëàñü íà 18-20 äîáó ³ ïðîÿâëÿëàñü ó çìåíøåíí³ ðóõîâî¿ àêòèâíîñò³. Çàãèáåë³ òâàðèí íå â³äì³÷åíå. Êîåô³ö³ºíò êóìóëÿö³¿ ïåðåâèùóº 8,0 ³ ñâ³ä÷èòü ïðî ñëàáêó êóìóëÿòèâíó àêòèâí³ñòü ³êàðèäèíó.

Äëÿ âñòàíîâëåííÿ ïîðîãîâî¿ êîíöåíòðàö³¿ ³êàðèäèíó ïðè õðîí³÷íîìó ³íãàëÿö³éíîìó âïëèâîâ³ (Limch) ïðîâîäèëè ³íòðàíàçàëüíå çàòðóºííÿ á³ëèõ ùóð³â óïðîäîâæ 4 ì³ñÿö³â â äîçàõ, ùî â³äïîâ³äàëè êîíöåíòðàö³ÿì 16 ìã/ì³; 40 ìã/ì³; 120 ìã/ì³.

Äëÿ âèçíà÷åííÿ òîêñè÷íî¿ ä³¿ ³êàðèäèíó íà îðãàí³çì òâàðèí ó õðîí³÷íîìó åêñïåðèìåíò³ îáðàíî íàñòóïí³ êðèòåð³¿: çàãàëüíèé ñòàí òà âàãà òâàðèí, ìîðôîëîã³÷í³ ïîêàçíèêè âíóòð³øí³õ îðãàí³â, çì³íè ãåìàòîëîã³÷íèõ òà á³îõ³ì³÷í³ ïîêàçíèê³â.

Âïëèâ ïðåïàðàòó óïðîäîâæ åêñïåðèìåíòó íå âèêëèêàâ â³ðîã³äíèõ çì³í á³îõ³ì³÷íèõ ïîêàçíèê³â ó ïîð³âíÿíí³ ç êîíòðîëüíîþ ãðóïîþ. Ïàòîëî㳿 ðåñï³ðàòîðíèõ øëÿõ³â òà ïàðåíõ³ìàòîçíèõ îðãàí³â íå âèÿâëåíî.

Ó ï³ääîñë³äíèõ òâàðèí, ÿêèõ ï³ääàâàëè âïëèâó ðå÷îâèíè â êîíöåíòðàö³ÿõ 120 ìã/ì³ ³ 40 ìã/ì³, ñòàòèñòè÷íî äîñòîâ³ðíî çìåíøóâàëàñÿ ìàñà ò³ëà.

гâåíü âïëèâó ïðåïàðàòó 16 ìã/ì³ íå âèêëèêàâ çì³í ìàñè ò³ëà ó òâàðèí.

Çà âåëè÷èíó Limch ïðèéíÿòà êîíöåíòðàö³ÿ ³êàðèäèíó 40 ìã/ì³.

Îö³íêó ñåíñèá³ë³çóþ÷èõ âëàñòèâîñòåé ³êàðèäèíó ïðîâîäèëè íà ìóð÷àêàõ. Äëÿ äîñë³äæåííÿ àëåðãî÷óòëèâîñò³ òà ³ìóíîòîëåðàíòíîñò³ áóâ îáðàíèé ìåòîä îäíîðàçîâîãî ââåäåííÿ ðå÷îâèíè ó âíóòð³øíþ ïîâåðõíþ âóõà ìîðñüêèõ ñâèíîê ç ïîäàëüøèìè ùîäåííèìè àïë³êàö³ÿìè íà äåï³ëüîâàí³ ä³ëÿíêè áîêîâî¿ ïîâåðõí³ øê³ðè óïðîäîâæ 10 äí³â ç ìåòîþ ïîñèëåííÿ éìîâ³ðíî¿ ñåíñèá³ë³çàö³¿.

Äëÿ âèÿâëåííÿ àëåðã³÷íî¿ ðåàêö³¿ ñïîâ³ëüíåíîãî òèïó âèçíà÷àëè çì³íè ïîêàçíèê³â ïåðèôåðè÷íî¿ êðîâ³ (åðèòðîöèòè, ëåéêîöèòè ãåìîãëîá³í òà ëåéêîöèòàðíà ôîðìóëà). Îêð³ì öüîãî äëÿ ê³ëüê³ñíî¿ îö³íêè ñåíñèá³ë³çàö³¿ âèêîðèñòîâóâàëè ìåòîä ç âèÿâëåííÿ ðåàêö³¿ êë³òèí êðîâ³ íà àëåðãåí «in vitro» - ðåàêö³þ ñïåöèô³÷íî¿ àãëîìåðàö³¿ ëåéêîöèò³â (ÐÑÀË) ³ ðåàêö³þ ñïåöèô³÷íîãî ë³çèñó ëåéêîöèò³â (ÐÑËË).

Ó ñåíñèá³ë³çîâàíèõ òâàðèí â³äì³÷åíå äîñòîâ³ðíå çá³ëüøåííÿ àáñîëþòíî¿ ê³ëüêîñò³ ³ âì³ñòó åîçèíîô³ë³â, íåéòðîô³ë³â ³ àáñîëþòíî¿ ê³ëüêîñò³ ë³ìôîöèò³â ó ïîð³âíÿíí³ ç ïîêàçíèêàìè òâàðèí êîíòðîëüíî¿ ãðóïè. ²íäåêñè ñï³ââ³äíîøåííÿ ë³ìôîöèò³â äî ìîíîöèò³â (²ÑËÌ) òà ñï³ââ³äíîøåííÿ íåéòðîô³ë³â äî ìîíîöèò³â (²ÑÍÌ), ëåéêî-Ò-êë³òèííîãî òà ëåéêî- Â-êë³òèííîãî ³íäåêñ³â äîñòîâ³ðíî çì³íèëèñÿ ó ñåíñèá³ë³çîâàíèõ òâàðèí ó ïîð³âíÿíí³ ç êîíòðîëüíîþ ãðóïîþ. Ïðîâåäåí³ àëåðãîòåñòè (ÐÑËË, ÐÑÀË, III²Í) äàëè äîñòîâ³ðí³ çì³íè ó ñåíñèá³ë³çîâàíèõ òâàðèí. Òàêîæ çðîñëà ê³ëüê³ñòü öèðêóëþþ÷èõ â êðîâ³ ³ìóííèõ êîìïëåêñ³â ó ñåíñèá³ë³çîâàíèõ òâàðèí ó ïîð³âíÿíí³ ç êîíòðîëüíîþ ãðóïîþ.

Äîñë³äæåííÿ âïëèâó ³êàðèäèíó íà ðåïðîäóêòèâíó ôóíêö³þ ïðîâåäåíî íà äâîõ ïîêîë³ííÿõ ùóð³â ç íàíåñåííÿì ðå÷îâèíè íà øê³ðó â äîçàõ 50, 100 àáî 200 ìã/êã ùîòèæíÿ, ïî÷èíàþ÷è ç 10 òèæí³â äî ñïàðþâàííÿ ³ ïðîäîâæóþ÷è äî â³äëó÷åííÿ äèòèí÷àò. Ðåçóëüòàòè äîñë³äæåííÿ ïîêàçàëè, ùî õðîí³÷íà ä³ÿ ³êàðèäèíó íà øê³ðó â äîçàõ äî 200 ìã/êã íå ïðèçâîäèòü äî ðåïðîäóêòèâíî¿ òîêñè÷íîñò³ [4].

Äîñë³äæåííÿ êàíöåðîãåííèõ âëàñòèâîñòåé ³êàð³äèíó ïðîâåäåíî ó õðîí³÷íèõ åêñïåðèìåíòàõ (18 ì³ñÿö³â) íà ìèøàõ ïðè íàäõîäæåíí³ éîãî ç êîðìîì. Äîêàç³â êàíöåðîãåííîñò³ íå îòðèìàíî [4].

Äëÿ îá´ðóíòóâàííÿ ãðàíè÷íî äîïóñòèìî¿ êîíöåíòðàö³¿ ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè íà ï³äñòàâ³ âñòàíîâëåíèõ ïàðàìåòð³â òîêñè÷íîñò³ áóëî ðîçðàõîâàíî êîåô³ö³ºíò çàïàñó çà ìåòîäèêîþ Ê.Ê. Ñèäîðîâà [5], ÿêèé ñòàíîâèòü 4 (òàáë. 1).

Òàáëèöÿ 1. Ðîçðàõóíîê êîåô³ö³ºíòà çàïàñó ïî Ê.Ê. Ñèäîðîâó (2 âàð³àíò) äëÿ îá´ðóíòóâàííÿ ÃÄÊ ³êàðèäèíó.

ßê ãðàíè÷íî äîïóñòèìó êîíöåíòðàö³þ ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè ðåêîìåíäîâàíî ð³âåíü 10 ìã/ì³, ïàðè + àåðîçîëü, 3 êëàñ íåáåçïåêè.

Äëÿ êîíòðîëþ çà âì³ñòîì ³êàðèäèíó ó ïîâ³òð³ ðîçðîáëåíî ìåòîäèêó âèì³ðþâàííÿ ìàñîâî¿ êîíöåíòðàö³¿ ðå÷îâèíè (MB ¹78-00146137:2022) ìåòîäîì ãàçî-ð³äèííî¿ õðîìàòîãðàô³¿ ç âèêîðèñòàííÿì åëåêòðîííî-çàõîïëþâàëüíîãî äåòåêòîðà çà äîïîìîãîþ êàï³ëÿðíî¿ êâàðöîâî¿ êîëîíêè DB-5. Àíàë³çóâàííÿ ïðîâîäÿòü øëÿõîì àñï³ðàö³¿ ïàð³â òà àåðîçîëþ ðå÷îâèíè ç êîíöåíòðóâàííÿì íà ïîñë³äîâíî ç'ºäíàí³ ô³ëüòð ÀÔÀ-ÕÏ-20 òà øâèäê³ñíèé ïîãëèíà÷ гõòåðà, çàïîâíåíèé àöåòîíîì. Ìàñîâó êîíöåíòðàö³þ ³êàðèäèíó îá÷èñëþþòü çà ãðàäóþâàëüíîþ õàðàêòåðèñòèêîþ çàëåæíîñò³ âåëè÷èíè àíàë³òè÷íîãî ñèãíàëó â³ä ê³ëüêîñò³ ðå÷îâèíè ó ãðàäóþâàëüíèê ðîç÷èíàõ. ×àñ âèêîíàííÿ ìåòîäèêè - 2 ãîäèíè, ðîáî÷èé ä³àïàçîí - â³ä 5,0 ìã/ì³ äî 20,0 ìã/ì³.

ðåïåëåíò ³êàðèäèí ïîâ³òðÿ

Âèñíîâêè

²êàðèäèí çà ïàðàìåòðàìè ãîñòðî¿ òîêñè÷íîñò³ ïðè îäíîðàçîâîìó âíóòð³øíüîøëóíêîâîìó ââåäåíí³ òà îäíîêðàòíîìó ³íãàëÿö³éíîìó âïëèâîâ³ â³äíîñèòüñÿ äî ïîì³ðíî íåáåçïå÷íèõ ðå÷îâèí, ïðè îäíîêðàòíîìó íàíåñåíí³ íà øê³ðó - äî ìàëîíåáåçïå÷íèõ ðå÷îâèí, íå âîëî䳺 ðåçîðáòèâíî-òîêñè÷íîþ ³ ì³ñöåâî-ïîäðàçíþâàëüíîþ 䳺þ ïðè íàíåñåíí³ íà øê³ðó, ïðîÿâëÿº ñëàáêó ïîäðàçíþâàëüíó ä³þ ïðè ïîïàäàíí³ íà ñëèçîâ³ îáîëîíêè, ìîæå âèêëèêàòè ñåíñèá³ë³çàö³þ îðãàí³çìó, áåçïå÷íèé â ïëàí³ ðîçâèòêó â³ääàëåíèõ åôåêò³â âïëèâó. Ãðàíè÷íî äîïóñòèìà êîíöåíòðàö³ÿ ³êàðèäèíó ó ïîâ³òð³ ðîáî÷î¿ çîíè ðåêîìåíäóºòüñÿ íà ð³âí³ 10 ìã/ì³, ïàðè + àåðîçîëü, 3 êëàñ íåáåçïåêè. Ðîçðîáëåíî ìåòîäèêó âèì³ðþâàííÿ ìàñîâî¿ êîíöåíòðàö³¿ ³êàðèäèíó ó ïîâ³òð³.

References

1. U.S. National Library of Medicine [Internet]. Bethesda (MD): National Library of Medicine; 2004 [cited 2022 Jan 15]. PubChem. Icaridin.

2. European Convention for the Protection of Vertebrate Animals us ed for Experimental and Other Scientific Purposes: European Communities (EC) - Strasbourg, 18.III.1986. [Internet]. European Treaty Series ¹ 123.

3. [The procedure for research and experiments on animals by scientific institutions: Order of the Ministry of Education, Science, Youth and Sports of Ukraine dated March 1, 2012 ¹ 249]. [Ofitsiinyi Visnyk Ukrainy]. 2012;24:82. Ukrainian.

4. U.S. United States Environmental Protection Agency. Pesticides [Internet]. Fact Sheet for Picaridin; 2005 [cited 2022 Jan 15].

5. [Methodical guidelines for establishing indicative safe exposure levels of harmful substances in the air of the working area: approved by the Ministry of Health of the USSR from 15.09.85 ¹4000-85]. 1985:34. Ukrainian.

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