Acute oral, subacute, and developmental toxicity profiling of naphthalene 2-yl, 2-chloro, 5-nitrobenzoate: Assessment based on stress response, toxicity, and adverse outcome pathways

Anwar, Fareeha and Saleem, Uzma and Rehman, Atta Ur and Ahmad, Bashir and Ismail, Tariq and Mirza, Muhammad Usman and Ahmad, Sarfraz (2022) Acute oral, subacute, and developmental toxicity profiling of naphthalene 2-yl, 2-chloro, 5-nitrobenzoate: Assessment based on stress response, toxicity, and adverse outcome pathways. Frontiers in Pharmacology, 12. ISSN 1663-9812, DOI https://doi.org/10.3389/fphar.2021.810704.

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Abstract

The U.S. National Research Council (NRC) introduced new approaches to report toxicity studies. The NRC vision is to explore the toxicity pathways leading to the adverse effects in intact organisms by the exposure of the chemicals. This study examines the toxicity profiling of the naphthalene-2-yl 2-chloro-5-dinitrobenzoate (SF5) by adopting the vision of NRC that moves from traditional animal studies to the cellular pathways. Acute, subacute, and developmental toxicity studies were assayed according to the Organization for Economic Cooperation and Development (OECD) guidelines. The stress response pathway, toxicity pathway, and adverse effects outcome parameters were analyzed by using their standard protocols. The results showed that the acute toxicity study increases the liver enzyme levels. In a subacute toxicity study, alkaline phosphatase (ALP) levels were raised in both male and female animals. SF5 significantly increases the normal sperm count in the male animals corresponding to a decrease in the abnormality count. Developmental toxicity showed the normal skeletal and morphological parameters, except little hydrocephalus was observed in developmental toxicity. Doses of 20 mg/kg in males and 4 mg/kg in females showed decreased glutathione (GSH) levels in the kidney and liver. MDA levels were also increased in the kidney and liver. However, histopathological studies did not show any cellular change in these organs. No statistical difference was observed in histamine levels, testosterone, nuclear factor erythroid two-related factor-2 (Nrf2), and nuclear factor-kappa B (NF-kappa B), which showed no initiation of the stress response, toxicity, and adverse effect pathways. Immunomodulation was observed at low doses in subacute toxicity studies. It was concluded that SF5 did not produce abrupt and high-toxicity levels in organs and biochemical parameters. So, it is safe for further studies.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: SF5; Nrf2; Stress response pathway; Acute oral toxicity; Biochemical parameters; Oxidative stress markers
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 03 Aug 2022 00:24
Last Modified: 03 Aug 2022 00:24
URI: http://eprints.um.edu.my/id/eprint/33469

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