4.1 Article

METABOLISM AND IN VITRO ASSESSMENT OFTHE MUTAGENIC ACTIVITY OF URINARY EXTRACTS FROM RATS AFTER INHALATION EXPOSURE TO 1-METHYLNAPHTHALENE

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NOFER INST OCCUPATIONAL MEDICINE, POLAND
DOI: 10.13075/ijomeh.1896.01955

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rats; inhalation; micronucleus test; toxicokinetics; 1-methylonaphthalene; 1-naphthoic acid

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  1. Nofer Institute of Occupational Medicine

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This study investigated the distribution of 1-naphthoic acid (1-NA) in different tissues and urinary excretion after rats were exposed to 1-methylnaphthalene (1-MN) vapor. The results showed that the levels of 1-NA in the tissues were dependent on the exposure dose of 1-MN. The activity of cytochrome in the liver increased with the dose of 1-MN, and there was a significant increase in ALT activity in the serum of exposed rats. Furthermore, urine extracts from exposed rats resulted in a significant increase in the frequency of micronuclei compared to control animals.
Objectives: 1-Methylnaphthalene (1-MN) is composed of 2 benzene rings and belongs to polycyclic aromatic hydrocarbons. The metabolism of 1-MN in laboratory animals and bacteria leads to the formation of 1-naphthoic acid (1-NA). Material and Methods: In this study the distribution of 1-NA in lung, liver, spleen, kidney and urinary excretion of 1-NA in rats after single and repeated inhalation exposure to 1-MN vapors were in-vestigated. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cytochrome were measured of the rats. Genotoxic effects were evaluated with the in vitro micronucleus test on V79 hamster fibroblasts. Results: The concentrations of 1-NA in the tissues of rats after single and repeated exposure to 1-MN were dependent on the exposure dose. High levels of 1-NA were found in kidneys of animals after the single and repeated exposure to 1-MN. With an increase of 1-MN dose, an increase in the activity of cytochrome P450 (CYP1A1 and CYP1A2) was ob-served in the liver of rats. Compared to control animals, significantly higher ALT activity was noted in serum of rats exposed to 1-MN. The micronu-clei frequency in V79 cells exposed to 1-MN (in the range of analyzable concentrations; i.e., 5-25 lig/ml) did not differ significantly from the vehicle control, whereas urine extracts from rats exposed to 1-MN induced a significant increase in the frequency of micronuclei compared to urine extracts from the group of control animals. Conclusions: Metabolism of 1-MN in rats after the inhalation exposure leading to 1-NA was mainly observed during the first day after the end of exposure. It is likely that 1-MN metabolites present in rat urine can induce the increased micronuclei frequency as was shown in V79 cells. Int J Occup Med Environ Health. 2022;35(6):731 - 46

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