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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">toxreview</journal-id><journal-title-group><journal-title xml:lang="ru">Токсикологический вестник</journal-title><trans-title-group xml:lang="en"><trans-title>Toxicological Review</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0869-7922</issn><issn pub-type="epub">3034-4611</issn><publisher><publisher-name>Federal Scientific Center of Hygiene named after F.F. Erisman</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">toxreview-543</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group></article-categories><title-group><article-title>РЕАКЦИЯ ГЛУБОКИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ КРЫСЫ НА ОДНОКРАТНОЕ ИНТРАТРАХЕАЛЬНОЕ ВВЕДЕНИЕ НАНОЧАСТИЦ ОКСИДОВ НИКЕЛЯ И МАРГАНЦА ИЛИ ИХ КОМБИНАЦИИ И ЕЕ ОСЛАБЛЕНИЕ БИОПРОТЕКТОРНОЙ ПРЕМЕДИКАЦИЕЙ</article-title><trans-title-group xml:lang="en"><trans-title>LOWER AIRWAYS RESPONSE IN RATS TO A SINGLE OR COMBINED INTRATRACHEAL INSTILLATION OF MANGANESE AND NICKEL NANOPARTICLES AND ITS ATTENUATION WITH A BIO-PROTECTIVE PRE-TREATMENT</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кацнельсон</surname><given-names>Борис Александрович</given-names></name><name name-style="western" xml:lang="en"><surname>Katsnelson</surname><given-names>Boris Aleksandrovich</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, заведующий отделом токсикологии и биопрофилактики ФБУН ЕМНЦПОЗРПП, 620014, г. Екатеринбург</p><p>e-mail: bkaznelson@etel.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Минигалиева</surname><given-names>Ильзира Амировна</given-names></name><name name-style="western" xml:lang="en"><surname>Minigalieva</surname><given-names>Ilzira Amirovna</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат биологических наук, старший научный сотрудник отдела токсикологии и биопрофилактики ФБУН ЕМНЦПОЗРПП, 620014, г. Екатеринбург</p><p>e-mail: ilzira-minigalieva@yandex.ru</p><p> </p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Привалова</surname><given-names>Лариса Иванова</given-names></name><name name-style="western" xml:lang="en"><surname>Privalova</surname><given-names>Larisa Ivanovna</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, заведующая лабораторией научных основ биопрофилактики ФБУН ЕМНЦПОЗРПП, 620014, г. Екатеринбург</p><p>e-mail: privalovali@yahoo.com</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сутункова</surname><given-names>Марина Петровна</given-names></name><name name-style="western" xml:lang="en"><surname>Sutunkova</surname><given-names>Marina Petrovna</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат медицинских наук, старший научный сотрудник отдела токсикологии и биопрофилактики ФБУН ЕМНЦПОЗРПП, 620014, г. Екатеринбург</p><p>e-mail: sutunkova@ymrc.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гурвич</surname><given-names>Владимир Борисович</given-names></name><name name-style="western" xml:lang="en"><surname>Gurvich</surname><given-names>Vladimir Borisovich</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, директор ФБУН ЕМНЦПОЗРПП, 620014, г. Екатеринбург</p><p>e-mail: gurvich@ymrc.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шур</surname><given-names>Владимир Яковлевич</given-names></name><name name-style="western" xml:lang="en"><surname>Shur</surname><given-names>Vladimir Yakovlevich</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор физико-математических наук, профессор, директор Центра коллективного пользования «Современные нанотехнологии», 620000, г. Екатеринбург</p><p>e-mail: vladimir.shur@usu.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шишкина</surname><given-names>Екатерина Владимировна</given-names></name><name name-style="western" xml:lang="en"><surname>Shishkina</surname><given-names>Ekaterina Vladimirovna</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат физико-математических наук, старший научный сотрудник Центра коллективного пользования «Современные нанотехнологии», 620000, г. Екатеринбург</p><p>e-mail: ekaterina.shishkina@labfer.usu.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вараксин</surname><given-names>Анатолий Николаевич</given-names></name><name name-style="western" xml:lang="en"><surname>Varaksin</surname><given-names>Anatoliy Nikolayevich</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор физико-математических наук, профессор, главный научный сотрудник лаборатории математического моделирования в экологии и медицине Института промышленной экологии, нанотехнологии, 620990, г. Екатеринбург,</p><p>e-mail: varaksin@ecko.uran.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Панов</surname><given-names>Владимир Григорьевич</given-names></name><name name-style="western" xml:lang="en"><surname>Panov</surname><given-names>Vladimir Grigoryevich</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат физико-математических наук, зав. лабораторией математического моделирования в экологии и медицине Института промышленной экологии, нанотехнологии, 620990, г. Екатеринбург</p><p>e-mail: panov@ecko.uran.ru</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Budgetary Science Institution«Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers»</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Центр коллективного пользования «Современные нанотехнологии» Уральского федерального университета</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Centre for Shared Use «Modern Nanotechnologies» of the Ural Federal University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБУН «Институт промышленной экологии УрО» РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Industrial Ecology, Ural Branch of the Russian Academy of Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>22</day><month>11</month><year>2021</year></pub-date><volume>0</volume><issue>6</issue><fpage>8</fpage><lpage>14</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Кацнельсон Б.А., Минигалиева И.А., Привалова Л.И., Сутункова М.П., Гурвич В.Б., Шур В.Я., Шишкина Е.В., Вараксин А.Н., Панов В.Г., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Кацнельсон Б.А., Минигалиева И.А., Привалова Л.И., Сутункова М.П., Гурвич В.Б., Шур В.Я., Шишкина Е.В., Вараксин А.Н., Панов В.Г.</copyright-holder><copyright-holder xml:lang="en">Katsnelson B.A., Minigalieva I.A., Privalova L.I., Sutunkova M.P., Gurvich V.B., Shur V.Y., Shishkina E.V., Varaksin A.N., Panov V.G.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.toxreview.ru/jour/article/view/543">https://www.toxreview.ru/jour/article/view/543</self-uri><abstract><p>Оксид никеля (II) и разнообразные химические формы марганца, включая оксид марганца (II, III), могут присутствовать вместе в субмикронной фракции сварочного дыма. Мы приготовили с помощью лазерной абляции в деионизированной воде металлических пластинок 99,99% чистоты суспензии наночастиц NiO со средним диаметром (±σ) 30±12 нм и Mn3O4 32±10 нм. Эти суспензии вводились интратрахеально крысам одна немедленно после другой в чередующейся последовательности или же изолированно (при этом для второго введения использовалась вода), и через 24 часа мы получали жидкость бронхоальвеолярного лаважа (БАЛЖ). Увеличение общей клеточности БАЛЖ, числа альвеолярных макрофагов (АМ) и нейтрофильных лейкоцитов (НЛ), а особенно отношения НЛ/АМ (которое является надёжным сравнительным индексом цитотоксичности введенных частиц) было значительно выше при действии NiO, чем при действии Mn3O4. Полуконтактная атомно-силовая микроскопия топографии поверхности клеток продемонстрировала активный эндоцитоз наночастиц NiO и Mn3O4 лёгочными фагоцитами. Более высокая пульмонарная цитотоксичность наночастиц NiO по сравнению с наночастицами Mn3O4 была показана также по увеличению активности некоторых лизосомиальных энзимов в БАЛЖ. Математический анализ выявил субаддитивное комбинированное действие NiO и Mn3O4, судя по клеточным показателям, в то время как по разным биохимическим – аддитивность, субаддитивность либо синергизм. У крыс, которые в течение 4 недель перед введением NiO+Mn3O4 (по 0,25 мг каждого) получали перорально глютамат, глицин, ацетил-цистеин, иод и селенсодержащий поливитаминный препарат, наночастицы вызвали существенно менее выраженную мобилизацию НЛ, чем при такой же экспозиции без премедикации.</p></abstract><trans-abstract xml:lang="en"><p>Nickel(II) oxide and multiple manganese species [manganese(II, III) oxide included], may be jointly present in welding fumes submicron fraction. Using laser ablation of 99.99% pure metallic plates in deionized water, suspensions of NiO and Mn3O4 nanoparticles with mean (±σ) diameters 30±12 nm and 32±10 nm respectively were created. Both suspensions were instilled intratracheally to rats, one immediately after another in alternating sequence or separately (another instillation being with water). The broncho alveolar lavage fluid (BALF) was obtained 24 h after. The increase in total BALF cells, alveolar macrophages (AM) and neutrophil leukocytes (NL) counts and especially in the NL/AM ratio (which is a reliable сomparison index of instilled particles cytotoxicity) was significantly higher at exposure to NiO than to Mn3O4. Semi-contact atomic force microscopy of cell surface topography demonstrated active endocytosis of NiO and Mn3O4 nanoparticles by pulmonary phagocytes. The higher pulmonary cytotoxicity of NiO as compared with Mn3O4 nanoparticles was also shown by increase in some lysosomal enzyme activities. Mathematical analysis revealed a sub-additive combined action of NiO and Mn3O4, judging by cellular indices, while judging by different biochemical indices additivity, sub-additivity or synergism were shown. In rats fed glutamate, glycine, acetyl cysteine, iodide and a Se-containing multivitamin preparation orally during 4 weeks before exposure to NiO+Mn3O4 (0.25 mg each), the latter evoked a significantly weaker NL recruitment than in rats so exposed without pretreatment.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>наночастицы</kwd><kwd>оксид никеля</kwd><kwd>оксид марганца</kwd><kwd>бронхоальвеолярный лаваж</kwd><kwd>лёгочая цитотоксичность</kwd><kwd>комбинированное действие</kwd><kwd>биопротекторы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>nanoparticles</kwd><kwd>nickel oxide</kwd><kwd>manganese oxide</kwd><kwd>bronchoalveolar lavage</kwd><kwd>pulmonary cytotoxicity</kwd><kwd>combined action</kwd><kwd>bioprotectors</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Кацнельсон Б.А. Комбинированное действие химических веществ. В кн.: Общая токсикология (ред. Б.А. Курляндский, В.А. Филов). М.: Медицина. 2002: 497–520.</mixed-citation><mixed-citation xml:lang="en">Katsnelson B.A. Combined action of chemicals. In: Kurlyandsky BA, Filov VA (eds.). Moscow: «Meditsina» Publishers, 2002: 497-520 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Varaksin A.N., Katsnelson B.A., Panov V.G., Privalova L.I., Kireyeva E.P., Valamina I.E., Beresneva O.Yu. Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead. Food Chem. Toxicol. 2014; 64: 144–156.</mixed-citation><mixed-citation xml:lang="en">Varaksin A.N., Katsnelson B.A., Panov V.G., Privalova L.I., Kireyeva E.P., Valamina I.E., Beresneva O.Yu. Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead. Food Chem. Toxicol. 2014; 64: 144-156.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Keane M., Stone S., Chen B. Welding fumes from stainless steel gas metal arc processes contain multiple manganese chemical species. J. Environ. Monit. 2010; 12: 1130–1140.</mixed-citation><mixed-citation xml:lang="en">Keane M., Stone S., Chen B. Welding fumes from stainless steel gas metal arc processes contain multiple manganese chemical species. J. Environ. Monit. 2010; 12: 1130-1140.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Taube F. Manganese in occupational arc welding fumes – aspects on physiochemical properties, with focus on solubility. Ann. Occup. Hyg. 2012; 57: 6–25.</mixed-citation><mixed-citation xml:lang="en">Taube F. Manganese in occupational arc welding fumes - aspects on physiochemical properties, with focus on solubility. Ann. Occup. Hyg. 2012; 57: 6-25.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Andujar P., Simon-Deckers A., GalateauSalle F., Fayard B., Beaune G., Clin B., Billon-Galland M-A., Durupthy O., Pairon J-C., Doucet J., et al. Role of metal oxide nanoparticles in histopathological changes observed in the lung of welders. Part. Fibre Toxicol. 2014; 11: 23.</mixed-citation><mixed-citation xml:lang="en">Andujar P., Simon-Deckers A., Galateau-Salle F., Fayard B., Beaune G., Clin B., Billon-Galland M-A., Durupthy O., Pairon J-C., Doucet J., et al. Role of metal oxide nanoparticles in histopathological changes observed in the lung of welders. Part. Fibre Toxicol. 2014; 11: 23.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Katsnelson B.A., Privalova L.I., Kuzmin S.V., Degtyareva T.D., Sutunkova M.P., Yeremenko O.S., Minigalieva I.A., Kireyeva E.P., Khodos M.Y., Kozitsina A.N., et al. Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: Are we defenseless against nanoparticles? Int. J. Occup. Environ. Health. 2010; 16: 508–524.</mixed-citation><mixed-citation xml:lang="en">Katsnelson B.A., Privalova L.I., Kuzmin S.V., Degtyareva T.D., Sutunkova M.P., Yeremenko O.S., Minigalieva I.A., Kireyeva E.P., Khodos M.Y., Kozitsina A.N., et al. Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: Are we defenseless against nanoparticles? Int. J. Occup. Environ. Health. 2010; 16: 508-524.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Katsnelson B.A., Privalova L.I., Degtyareva T.D., Sutunkova M.P., Yeremenko O.S., Minigalieva I.A., Kireyeva E.P., Kozitsina A.N., Malakhova N.A., Glazyrina J.A., et al. Experimental estimates of the toxicity of iron oxide Fe3O4 (magnetite) nanoparticles. Cent. Eur. J. Occup. Environ. Med. 2010; 16: 47–63.</mixed-citation><mixed-citation xml:lang="en">Katsnelson B.A., Privalova L.I., Degtyareva T.D., Sutunkova M.P., Yeremenko O.S., Minigalieva I.A., Kireyeva E.P., Kozitsina A.N., Malakhova N.A., Glazyrina J.A., et al. Experimental estimates of the toxicity of iron oxide Fe3O4 (magnetite) nanoparticles. Cent. Eur. J. Occup. Environ. Med. 2010; 16: 47-63.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Katsnelson B.A., Privalova L.I., Gurvich V.B., Makeyev O.H., Shur V.Y., Beikin J.B., Sutunkova M.P., Kireyeva E.P., Minigalieva I.A., Loginova N.V., et al. Comparative in vivo assessment of some adverse bio-effects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver’s effects with a complex of innocuous bioprotectors. Int. J. Mol. Sci. 2013; 14: 2449–2483.</mixed-citation><mixed-citation xml:lang="en">Katsnelson B.A., Privalova L.I., Gurvich V.B., Makeyev O.H., Shur V.Y., Beikin J.B., Sutunkova M.P., Kireyeva E.P., Minigalieva I.A., Loginova N.V., et al. Comparative in vivo assessment of some adverse bio-effects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver’s effects with a complex of innocuous bioprotectors. Int. J. Mol. Sci. 2013; 14: 2449-2483.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Привалова Л.И., Кацнельсон Б.А., Логинова Н.В., Гурвич В.Б., Шур В.Я., Бейкин Я.Б., Сутункова М.П., Минигалиева И.А., Шишкина Е.В., Пичугова С.В., Тулакина Л.Г., Беляева С.В., Рузаков В.О. Цитологические и биохимические особенности жидкости, получаемой при бронхо-альвеолярном лаваже у крыс после интратрахеального введения наноразмерных меднооксидных частиц // Токсикол. вестник. 2014; № 5.</mixed-citation><mixed-citation xml:lang="en">Privalova L.I., Katsnelson B.A., Loginova N.V., Gurvich V.B., Shur V.Y., Beikin J.B.et al. Cytological and biochemical characteristics of bronchoalveolar lavage fluid in rats after intratracheal instillation of nano-scale copper oxide particles. Toxic. Vestnik. 2014; 5 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Gessner P.K. Isobolographic analysis of interactions: an update on applications and utility. Toxicology. 1995; 105: 161–179.</mixed-citation><mixed-citation xml:lang="en">Gessner P.K. Isobolographic analysis of interactions: an update on applications and utility. Toxicology. 1995; 105: 161-179.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Privalova L.I., Katsnelson B.A., Osipenko A.B., Yushkov B.H., Babushkina L.G. Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity. Environm. Health Perspect.1980; 35: 205–218.</mixed-citation><mixed-citation xml:lang="en">Privalova L.I., Katsnelson B.A., Osipenko A.B., Yushkov B.H., Babushkina L.G. Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity. Environm. Health Perspect.1980; 35: 205-218.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Katsnelson B.A., Privalova L.I. Recruitment of phagocytizing cells into the respiratory tract as a response to the cytotoxic action of deposited particles. Environ. Health Perspect.1984; 55: 313–325.</mixed-citation><mixed-citation xml:lang="en">Katsnelson B.A., Privalova L.I. Recruitment of phagocytizing cells into the respiratory tract as a response to the cytotoxic action of deposited particles. Environ. Health Perspect.1984; 55: 313-325.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Gennings C. On testing for drug/ chemical interaction: definitions and inference. J. Biopharm. Stat. 2000; 10(4): 457–467.</mixed-citation><mixed-citation xml:lang="en">Gennings C. On testing for drug/ chemical interaction: definitions and inference. J. Biopharm. Stat. 2000; 10(4): 457-467.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Кацнельсон Б.А., Балезин С.Л., Давыдова В.И., Неизвестнова Е.М., Привалова Л.И., Конышева Л.И. Закономерности, экспериментальные и математические методы оценки комбинированного токсического действия металлов. Материалы докладов пленумов правлений Всесоюзного и армян. науч. обществ токсикологов, посвященные вопросам комбинированного действия химических веществ на организм. Ереван, 1989:14–17.</mixed-citation><mixed-citation xml:lang="en">Katsnelson D.A., Balesin S.L., Davydova V.I., Neisvestnova E.M., Privalova L.I., Konysheva L.I. General patterns, experimental and mathematical methods of assessing combined toxicity of metals. In: «Proceedings of the plenary meetings of executive boards of the All-Union and Armenian Toxicological Societies dedicated to the problem of combined action of chemicals on the organism», Yerevan, 1989: 14-17 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Donaldson K., Bolton R., Jones E. A., Brown G. M., Robertson M. D., Slight J., Cowie H., Davis J.M.G. Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.Thorax. 1988;43: 525–533.</mixed-citation><mixed-citation xml:lang="en">Donaldson K., Bolton R., Jones E.A., Brown G.M., Robertson M.D.,Slight J., Cowie H., Davis J.M.G. Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide. Thorax. 1988;43: 525-533.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Q., Yukinori K., Sato K., Nakakuki K., Koyahama N., Donaldson K. Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. J. Toxicol. Environ. Health. 1998; 53: 423–438.</mixed-citation><mixed-citation xml:lang="en">Zhang Q., Yukinori K., Sato K., Nakakuki K., Koyahama N., Donaldson K. Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. J. Toxicol. Environ. Health. 1998; 53: 423-438.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Q., Yukinori K., Zhu X., Sato K., Mo Y., Kluz T., Donaldson K. Comparative toxicity of standard nickel and ultrafine nickel after intratracheal instillation. J. Occip. Health. 2003; 45: 23–30.</mixed-citation><mixed-citation xml:lang="en">Zhang Q., Yukinori K., Zhu X., Sato K., Mo Y., Kluz T., Donaldson K. Comparative toxicity of standard nickel and ultrafine nickel after intratracheal instillation. J. Occip. Health. 2003; 45: 23-30.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
