ACUTE TOXICITY OF GENERIC AND IN VITRO REFERENCE TOXICAMOL USING THE ARTEMIA SALINE TOXICITY BIOINDICATOR LEACH

: This study aims to analyze, through an experimental study with a quantitative and descriptive approach, the toxicity and identification of the 50% Lethal Concentration (LC50) of the reference and generic paracetamol drops, both commercially available and produced in Brazil, comparing them with each other. The lethality test was performed on Artemia salina according to the methodology described by Meyer (1982), with some modifications. When performing the toxicity test on Artemia salina, for generic paracetamol, the LC50 obtained after 24 hours was 998.3 ± 0.2μg/ mL. The reference paracetamol presented LC50 of 612.2 ± 1.3μg/mL. Based on the analysis of this research, it was found that the reference paracetamol presented signs of toxicity in nauplii of the microcrustacean Artemia salina, presenting a LC50 ≤1000μg/mL. Generic paracetamol showed a LC50 ≤1000μg/mL with a range above 1000 ug/mL indicating non-toxicity for this sample.


INTRODUCTION
Paracetamol or acetaminophene is a drug considered safe and effective, with analgesic and antipyretic properties, with poor anti-inflammatory action, to relieve light to moderate pain, being effective for all age groups (BRAYNER, SILVAEALMEIDA, 2018).It is a low -cost and low -cost drug (Mezarobba and Bitencourt, 2018).
Because it is a medicine that does not require medical prescription there is a high index of indiscriminate use.Despite being considered safe and effective in its therapeutic doses, but when consumed at doses higher than the recommendation it can cause hepatotoxicity.(Ribeiro et al. 2023).
Paracetamol -induced poisoning happens more frequently in young people 15 to 24 years old, individuals who make abuse of alcohol and individuals aged 40 years of 40 years occur at high risk, the hepatic failure and may be fatal, and may be fatal.(SILVA JUNIOR et al;2019).
There are several pharmaceutical presentations sold, among them: tablets, oral solution, suppositories and injectables (RIBEIRO et al, 2023).Due to ease and broad use in Brazil, it is important to evaluate the pharmacological patterns of acetomiphene.The variability of laboratories, forms of presentation and classification of the drug (reference, generic, similar and manipulated), suggests a diversity in the quality standard of this, and it is necessary to evaluate such criteria to avoid possible health damage (Teixeira, 2016).
In Brazil, according to Law 9,787 of February 10, 1999, the drugs considered "reference" are innovative products whose effectiveness, safety and quality were scientifically proven with the competent federal agency, at the time of registration.Upon protection period of the reference product patent, generic and similar drugs can be produced that, similar to the reference, follow the principles of bioequivalence and bioavailability to obtain the same therapeutic effect for later records and commercial use (.(Brazil, 1999;.Lopes;Costa, 2016, Garcez et al., 2019).
Soline artemia is a species of microcrustacean of the order years, found in Salgadas waters (Carvalho et al., 2008).It is used as a living food for fish, and its eggs are found in aquarizers stores and Thus, this work aimed to evaluate the toxicity of the acetaminopus drops: generic and reference, in A. saline model.

METHODOLOGY
This work resulted from an experimental study, with quantitative and descriptive approach, which evaluated toxicity and identified the lethal concentration 50% (CL50) of acetaminophen (oral solution) reference and generic, both commercially available and produced in Brazil, comparing them each other.
The lethality test was held in Artemia Salina, cultivated at the Food Analysis/Sanitation Analysis Laboratory of the Federal Institute of Piauí-IFPI/CTZS, according to the methodology described by Meyer (1982), with some modifications.
The specimens were distributed in three specimens for each concentration of brand and generic acetaminophen, as well as negative control with artificial marine water and positive control with 0.0006 mg/ml of copper sulfate (COSO4).
The tubes were left at room temperature for 24 hours.After this period, the number of surviving cassaways was held.They were observed near a light source and considered alive all those

1
Doctor, Pediatry resident-federal university of Piauí-UFPI 2 Pediatry resident-federal university of Piauí-UFPI 3 Doctor, Pediatry resident-federal university of Piauí-UFPI 4 PhD in Biotechnology at the Federal University of Piauí -UFPI ISSN: 2763-5724 / Vol.04 -n 04 -ano 2024 is widely used in toxicological studies due to low cost and easy cultivation.Several works have been trying to correlate toxicity over A. saline with antifungal, viruscid, antimicrobial, tripanosomicide and parasiticide activities.Lethality tests are done in toxicological tests and the median lethal concentration (Cl50) indicates death in half a sample (BEDNARCZUK, 2010).