Epidemiological profile of exogenous intoxications occurred in the State of Rio Grande do Sul between the years 2007 and 2020

Introduction: Exogenous intoxication occurs when humans eat, inhale or are exposed to chemicals that can harm their health. Objective: To characterize the epidemiological profile of cases of exogenous intoxications reported to the epidemiological surveillance of the State of Rio Grande do Sul between 2007 and 2020. Method: For this, data from the Notifiable Diseases Information System (Sinan-Net) were used. The information collected was evaluated in terms of socioeconomic characteristics and aspects related to the intoxication event itself. Results: The confirmed cases were 34,953 during the period evaluated. The most affected people were: female, people with incomplete primary education, people aged between 20 and 39 years who lived in cities. About the intoxications themselves, the most prevalent toxic agents were medicines and the category of circumstance of intoxication with the highest incidence was the suicide attempt. Most cases were clinically confirmed and were not related to work exposure, and 73.30% of cases were cured without sequelae. However, there was a high number of information described as ignored for several categories. Information like schooling is usually not filled because it is not relevant to diagnosis. Conclusions: Therefore, it is necessary to improve the quality of information, so that it is possible to identify the most affected categories and develop adequate prevention measures.


INTRODUCTION
Exogenous intoxication is a public health problem and can be defined as a clinical manifestation of the harmful effects produced by some (exogenous) chemical substance in a living organ-ism¹.Several toxic agents are associated to exogenous intoxication.Accidental or intentional ingestion and super dosage of drugs and pesticides can lead to controversial diagnoses and motivate cases of underreporting due to the lack of information by the population about the danger of intoxications.
In the world, among the most frequently involved substances in intoxications are pesticides, which in developing world countries correspond to 90% of cases of intoxication.In developed countries the use of medicines reaches 60% of cases².In Brazil, the suicide attempt by exogenous intoxication is alarming.In the years 1998 to 2009, poisoning by ingestion of toxic products corresponded to approximately 70% of the total reported cases.Of the 112,295 hospitalizations due to attempted suicide, 78,606 were due to exogenous intoxication³.Accidental poisoning in children generates a high rate of deaths every year 4 .In 2013 at least 50% of poisonings recorded in Fiocruz's National System of Toxic-Pharmacological Information (Sinitox) occurred in children under 20, with 29% of cases in children from one to four years old 5 .
People under 40 years old seem to be more vulnerable to poisoning, and females have a higher incidence among cases.Medication intake has become one of the most prevalent causes in recent years in the state of Rio Grande do Sul, followed by pesticides.The lack of information about the use of medicines can lead to accidental poisoning, especially in homes, as a result of error in administration.Pesticides are easily accessible and when used improperly they can expose human to serious poisoning.However, the main and most worrying factor is suicide attempts using drugs and other chemicals, in cases of intentional causes.
Due to the population's lack of information on the subject and the importance of studying aspects of exogenous intoxications in Brazil, in addition to determining which are the main toxic agents responsible for cases of poisoning, this study also aimed to identify which categories of the population are most affected and under what circumstances these intoxications occur.
The investigation was carried out through notifications of confirmed cases of poisoning reported to epidemiological surveillance of Rio Grande do Sul between 2007 and 2020.Thus, with the knowledge of which part of the population is the most affected by this important public health problem, it is possible for the state to direct its resources more effectively, guiding those who are more susceptible to poisoning and preventing more cases from occurring.

METHOD
A cross-sectional observational analytical quantitative study of cases of exogenous intoxication reported to surveillance of Rio Grande do Sul in the period between 2007 and 2020 was carried out, using data from the Notifiable Diseases Information System (Sinan-Net).This system incorporates a list of notifiable diseases and conditions, using a standardized form in which data on the individual, symptoms, need for hospitalization, laboratory tests and final classification of the case are recorded.The registration instrument is the Sinan-Net notification form, which is filled in by health professionals and later sent to the epidemiological surveillance centers.

Data collection
Secondary data, obtained from the investigation of confirmed cases of exogenous intoxications reported to surveillance of Rio Grande do Sul in the period between 2007 and 2020, were collected.The information was tabulated and evaluated as socioeconomic characteristics (gender, age group, education, area of residence and state administrative area) and aspects related to the intoxication event itself (toxic agent, circumstances of intoxication, exposure at work, confirmation criteria, final classification and evolution of the patient's condition).The analysis and interpretation of variables were performed in an Excel spreadsheet, calculating the annual frequency of the criteria evaluated.

Descriptive data analysis
Some of the agents involved in cases notified to Sinan-Net were: medicines, agricultural pesticides, household pesticides, public health pesticides, rodenticides, veterinary products, household products, cosmetics, chemicals, metal, drugs of abuse, toxic plants, food, drinks, among others.The socioeconomic data analyzed in this study were: sex, education, age group, area of residence and state administrative division.The aspects of intoxication researched were: toxic agent, circumstances of intoxication, exposure at work, confirmation criteria, final classification of intoxication and evolution of the condition.

Ethical considerations
This research was carried out with secondary data, collected and used only for its purposes, with the information being presented collectively, without any prejudice to the people involved, especially with regard to the mention of people affected.These data will be under the custody of the researchers, their secrecy and confidentiality being guaranteed.

RESULTS AND DISCUSSION
Exogenous intoxication occurs when humans eat, inhale or are exposed to chemicals that can harm their health.This study aimed to characterize the epidemiological profile of cases of exogenous intoxications reported to the epidemiological surveillance of the State of Rio Grande do Sul between 2007 and 2020.
For this, data from the Sinan-Net which made it possible to identify an epidemiological profile of the cases involved.
The total of confirmed cases of exogenous intoxication reported in Rio Grande do Sul was 34,953(Figure 1).The years that present the highest rates of reported cases were 2019 (22.97% that were 8,032 of 34,953 cases); 2018 (18.57% that were 6,493 of 34,953 cases) and 2017 (14.44% that were 5,049 of 34,953 cases) (Figure 1).
The socioeconomic characteristics evaluated were sex, age group, schooling, residence (urban, rural or periurban) and state administrative area(Figure 2).In the sex category, 59.59% were the female (20,831 of the 34,953 cases), while 40.38% were male (14,116 of the 34,953 cases) (Figure 2A).Only 0.01% of the cases reported was ignored or did not respond (6 of 34,953 cases) this characteristic.During the study period, with the exception of the year 2013, all the others presented the highest occurrence in females.
The schooling of confirmed cases of exogenous intoxication is higher in elementary school, which corresponded to 14.96% (5,232 of the 34,953 cases), followed by complete high school education corresponding to 13.31% (4,655 of the 34,953 cases) (Figure 2B).The age groups evaluated in the study ranged from over 1 year to over 80 years of age, and the highest rates occurred between 20-39 years, about 42.36% of cases (14,809   of 34,953 cases), followed by age between 40-59 years, 23.67% (8,275 of 34,953 cases), and 14.03% (4,907 of 34,953 cases), between 15-19 years old(Figure 2C).
Regarding the area of residence, 80.35% of cases are in urban areas (28,085 of the 34,953 cases), and 15.16%, in rural areas (5,302 of the 34,953cases) (Figure 2D).About regions of state that occurs the notification, Passo Fundo presented 15.80% of all cases (5,523 of 34,953 cases), followed by Caxias do Sul, with 11.53% of cases (4,033 of 34,953cases) and Lajeado, 9.75% (3,410 of 34,953 cases) (Figure 2E).
As to the characteristics of the intoxication itself, the results were sequenced in: toxic agent, circumstances of intoxications, exposure at work, confirmation criteria, final classification and evolution of the patient's condition (Table ).
Among the data obtained for the category of toxic agent, the 15 main associated with the analyzed cases of exogenous intoxication were cited (Table ).The toxic agents with the highest reported incidence were drugs, corresponding to 50.04% (17,492  were clinically-epidemiologically confirmed, and 5.85% (2,045 of the 34,953 cases) were clinical-laboratory form.In the final classification category, confirmed intoxication corresponds to 57.57% of the cases (20,123 of the 34,953cases), while exposure alone corresponds to 26.73% (9,343 of the 34,953cases).Regarding the evolution of the patient's condition, 73.30% (25,623 of the 34,953cases) were cured without sequelae, while death from exogenous intoxication corresponded to 1.51% of the cases (530 of the 34,953cases), with its highest peak in 2013, with 265 patients.
As mentioned, the evaluation of the results indicated high rates of suicide attempts by medication, especially in females, which was also reported in other studies carried out in Brazil.Using research platforms like Web of Science and Scopus, which presented information collected in the Sinan-Net database, studies were obtained in the states of Minas Gerais 6 , Mato Grosso¹, Pernambuco 7 , Tocantins 8 and Rio Grande do Sul 9 .Data from other Source: Elaborated by the authors, 2022.reviews and case reports that could help in the study of exogenous intoxications were also extracted.
Analyzed the temporal trend of suicide mortality in the city of Uberaba, Minas Gerais, between 1996 and 2014 6 .This study analyzed 169 suicide attempts and 11 deaths from suicide.In female suicide attempts, the use of medication and poisoning between 15 and 29 years old stood out, and deaths by suicide in both sexes occurred mainly between 30 and 59 years old.For men, the main means of aggression were hanging followed by self-intoxication.
The ingestion of medication in households as a suicide attempt was 5.1 times more frequent in females compared to males.
In the state of Mato Grosso, an epidemiological study of children and adolescents in the municipality of Barra do Garças was car- Ingestion of low doses of GHB leads to euphoria, pain relief and antidepressant effects.High doses of GHB cause nausea, vomiting and loss of consciousness 13 .In cases of overdose of this drug, respiratory depression is frequently reported 14 .High consumption of alcohol can generate cross-reactivity in tests to detect GHB, and can influence to generate a false positive, as was the case of a 14-year-old patient transferred from another clinic to the pediatric intensive care unit with loss of consciousness, confirmed ethanol (alcoholic beverage) intoxication (3.3 g/L), and severe amnesia 15 .A similar case where ethanol resulted in a concentration of GHB much higher than expected was described 16 .This is important to realize when interpreting the results of the analysis, as the majority of patients ingesting GHB also ingested ethanol 15 .The discoloration of urine in acute cases of intoxication leaves it with a greenish appearance.Various data compiled from case reports, articles and reports point out that green discoloration can be caused by some substance abuse such as propofol, biliverdin, metoclopramide, amitriptyline, methocarbamol, indomethacin, promethazine, cimetidine, among other factors 17 .Some cases of drug capsule shell dyes may show signs of overdose, such as the suspicion of a case of intoxication by excessive ingestion of benzodiazepines carried out by the study by in which one patient showed the condition of green colored urine 17 .
Some athletes who practice strength sports, such as bodybuilding, are at greater risk of abusing drugs and hormones, such as exogenous insulin, a drug fraudulently used as an ergogenic resource with the aim of improving sports performance and recovery after exercise.However, when administered in high doses, athletes can enter into a condition of hypoglycemia 18 .Another important factor is hormone replacement therapy and the use of oral contraceptives, which are factors that can increase the risk of venous thromboembolism (VTE), and the risk depends on the dose of estrogen administered.Exogenous estrogen significantly increases the risk of VTE, whereas the amount of endogenous estrogen and testosterone does not increase the risk of embolism.Pulmonary embolism can be the result of a single intake of exogenous estrogen when administered in high dose, and may increase the risk of triggering VTE even in patients who are on therapeutic use.Therefore, it is important to question the use of these hormones in people who seek medical care with symptoms similar to pulmonary embolism 19 .
Exogenous intoxication from heavy metal poisoning (defined as the accumulation of any element that exhibits metallic characteristics at toxic levels in the soft tissues of the human body) can result in morbidity and mortality if not properly treated.
Even though this study showed a low incidence, approximately 0.21% (75 of 35,030 cases), this is an important contamination to be studied due to its cumulative effects on the body.The diagnosis is unusual in clinical practice, due to its complexity in the variations of symptoms presented by different types of metals, and the non-specific signs that can be confused with common diseases, making it an unfamiliar subject in the medical routine.
Inhalation of heavy metals such as lead and cadmium can occur through smoking, an exogenous source of contamination 20 .The rapid exchange between blood lead contents with the cardiovascular system and soft tissue components allows, on average, 90% to 99% of body lead to be associated with red blood cells, and the other part is closely related to environmental exposure.
This freely accessible part has toxic effects on various biological systems, inducing acute intoxication in organs 20,21 .Another commonly detected intoxication is by inadequate use of supplements.Vitamin D intoxication is considered rare in children and adolescents, and is often associated with errors in handling and the amount ingested daily.In the case reports 22 , in which the dose ranged from 40,000 to 560,000 IU/day, patients had severe hypercalcemia, hypercalciuria and nephrocalcinosis 22 .However, there are cases of vitamin D intoxication, even with consumption within the recommended daily dose 21 .Acute hypercalcemia in childhood can be due to several factors, ranging from inflammatory and infectious causes, as well as exogenous vitamin D intoxication 23 .In Brazil, a patient of 64-year-old retired woman Brodifacoum is a potent pesticide used to kill mice.Due to its anticoagulant effect, intoxication by this substance and vitamin K deficiency appear similarly in laboratory tests 24 .In a case Goulart JQ et al.Exogenous intoxications occurred in Rio Grande do Sul report, in which a woman was admitted to the hospital with persistent abdominal pain, diarrhea with no defined etiology, hematuria and anemia, after sending serum samples to the laboratory, levels of this rodenticide were found 24 .Patients who present disproportionate bleeding from an injury suffered, with elevated prothrombin time (PT) and partial thromboplastin time (PTT), without signs of disseminated intravascular coagulation and without a factor inhibitor as a cause, should be investigated for the possibility of poisoning by rodenticides 25 .
The high toxicity of pesticides in general is considered a public health problem.The organophosphates (OPP) that are used in plant protection, and their use as a source of poisoning, make them a constant danger.According to the study 26  present in brown sugar consumed was 3,000 times greater than the acceptable daily intake for this substance in humans (0.004 mg/kg/day) 27 .The presence of sulfite in this product was due to the intentional and illegal addition of sodium hydrosulfite in the production of rapadura, for whitening 27 .
Food poisoning is very common, especially among children.
The study 28 showed a case report of a 6-year-old girl who ingested about 10 beans of bitter lupine beans.When seeking care 1 hour after ingestion, the symptoms presented were headache, blurred vision, photophobia and nausea.The child recovered in approximately 12 hours, was discharged 24 hours after entering the Emergency Room, and in the one-month follow-up period remained asymptomatic 28 .Lupine beans are a food whose use is widespread throughout the world.Despite containing in its composition many nutrients such as proteins, fibers and vitamins, the bitter varieties of this food are rich in a kind of alkaloid, which are capable of causing acute anticholinergic syndrome in children and adults 28 .Therefore, the correct treatment of this food is important.The necessary recommendations for the correct handling of the bitter lupine are its immersion in water for 12 hours, followed by its cooking and, finally, washing for about 30 seconds, three times a day for five days before its consumption 29 .Intoxication caused by the ingestion of mushrooms can cause irritating gastroenterocolitis 30 .In Bulgaria, acute food poisoning has a high frequency and is responsible for 10.7% of hospitalizations.They affect both sexes and different ages to the same extent 30  cluded that the cause of his death was TTX contained in the liver of wild T. poecilonotus 33 .
One of the limitations faced in the data collected for this study, was the high number of information described as 'ignored', for several variables of the mentioned categories.This becomes an obstacle for substantiating the data.Some of the possible reasons may be related to registration problems, such as carelessness on the part of the professional responsible for filling in the intoxication form available or the population' absence of information.Thus, it is necessary to improve the quality of the registration of information so that underreported cases can be related to various social and cultural issues, among others.Exogenous intoxications are a public health problem, and anyone can be exposed to the risks of contamination, so it is essential to properly record data in order to draw an epidemiological profile of intoxications so that prevention measures can be developed.

CONCLUSIONS
Exogenous intoxications are a relevant public health problem, and it is essential to identify which part of the population is most affected, as well as the circumstances of intoxication with the highest incidence, so that adequate prevention measures can be developed.Suicide attempt was the circumstance of intoxication with the highest number of cases reported to Sinan-Net, followed by accidental intoxications.Thus, to avoid an increase in the number of cases of exogenous intoxication, the State of Rio Grande do Sul must provide psychological assistance to the population most susceptible to intoxication by suicide attempt, as well as alert and guide the population about the risks of accidental intoxication.This support is necessary for all those affected as a result of damage to the physical, mental and social health of each individual.It is also possible to reduce the number of information described as "ignored", which often occurs due to the population' absence absence of information.Such registration problems were one of the limitations faced during data collection in this study, as they may contribute to the diagnosis of some intoxications in which the symptoms are confused with other diseases.In addition to the population' lack of knowledge, the carelessness of the professional responsible for filling in the poisoning form is a factor that favors the lack of information about the cases.Therefore, it is also necessary to improve the quality of the registration of information in order to avoid underreporting and errors in the notification records.However, despite the registration problems, the article was successful in characterizing the epidemiological profile of cases of exogenous intoxication that occurred in the State of Rio Grande do Sul during the period studied, between 2007 and 2020.Still, more studies are needed about the subject that bring more information and enrich the discussion about this relevant public health problem so that it can be prevented.

Figure 1 .
Figure 1.Total of confirmed cases of exogenous intoxication reported in Rio Grande do Sul per year (2007-2020).
Goulart JQ et al.Exogenous intoxications occurred in Rio Grande do Sul Source: Elaborated by the authors, 2022.Socioeconomic characteristics evaluated were sex (A), age group (B), schooling (C), area of residence (urban, rural or periurban) (D) and state administrative area (E) notified in the period from 2007 to 2020.

Figure 2 .
Figure 2. Socioeconomic characteristics of patients involved in confirmed cases of exogenous intoxication reported in Rio Grande do Sul.
was admitted to the emergency department with postprandial food vomiting of undigested content and abdominal pain that worsened on palpation.Concomitantly, onset of sporadic frontal headache, fatigue, hyporexia, weight loss of 18 kg in the same period, intense pruritus, musculoskeletal pain in limbs and nocturia.Physical examination revealed hypertension (160/80 mmHg) and itchy macules on the lower limb.The dosage of vitamin D 25 OH and the diluted vitamin D test confirmed the diagnosis of hypervitaminosis D 24 .
Agricultural pesticides accounted for 8.38% of cases (2,931 of 34,953 cases), and in 2019, they affected 607 patients.Suicide attempt, of the 14 circumstances listed, had the highestincidence, 46.84% of the cases (16,375 of the 34,953 cases).There were 4,406 reported cases in 2019 attributed to this circumstance.The circumstance of accidental form corresponded to 22.90% of the cases (8,005 of the 34,953 cases), and ingestion of food corresponded to 1.85% of the cases (647 of the 34,953 cases).Work exposure to intoxicating agents happened in 14.78% of the cases (5,169 of the 34,953 cases).The confirmation criterion category shows that 57.98% of the cases (20,267 of the 34,953 cases) were only clinically confirmed, 22.70% (7,936 of the 34,953 cases)

Table .
Aspects of exogenous intoxications considering toxic agent, circumstances of intoxication, exposure at work, criteria of confirmation, final classification and evolution of sickness, by year.

048 1,180 2,554 1,726 2,235 2,848 5,049 6,493 8,032 2,012 34,953 Source
11llow: Main results identified and described in the text; Orange: Identified result and topic of discussion.546(80.6%)were male and 131 (19.4%) were female.The largest number of poisonings occurred in the age group up to 24 years (66%).Death was recorded in six (0.9%) patients.Most of the intoxications by narcotic drugs were in patients up to 44 years old, due to accidental or systematic use of narcotics.Opioids, like heroin, were the most cause of hospitalizations for drug poisoning in this study period11.
9.The age group was from 0 to 19 years and the period studied was from 2008 to 2013.Of the 125 cases of exogenous intox-In a study carried out in the Municipality of Moreno (state of Pernambuco), during the period from 2012 to 2015, the age, sex, type of toxic agent, use of pesticides and reason for exposure of individuals were analyzed affected by exogenous intoxications registered in Sinan.There were 109 cases of exogenous intoxication reported from 2012 to 2015, with the highest frequencies found in adults (51.1%).The main toxic agents corresponded to medicines (41.3%) and agricultural pesticides (12%).Of the 109 cases of exogenous intoxication, 37 (33.9%)occurreddue to attempted suicide 7 .Also, in the state of Pernambuco, cases of exogenous intoxication occurred in adolescents notified by the Centro de Assistência Toxicológica at a hospital in Recife/PE and, of the 25 cases of suicide attempts in the period from March to May 2010, 21 were female adolescents aged between 13 and 19 years.The exogenous intoxication by the use of pesticides was the most frequent (61.9%).These toxic substances are easily accessible, and their lack of control from production to commercialization increases the chances of intoxication 10 .85.52% lived in urban areas.Of the total number of reported cases, 1,038 cases (81.28%) of attempted suicide stand out9.In the city of Varna, Bulgaria, a study was carried out on acute intoxications by narcotic drugs between 1991 and 2015.This study reported that of the 677 patients intoxicated by narcotics, : Elaborated by the authors, 2022.*Ign:Ignored.Drug use is also an important cause of exogenous intoxicationand corresponded in this study to 3.80% of the cases (1,334 of the 35,030 cases).A study carried out with a case report of fatal intoxication by GHB (γ -hydroxybutyric), called "drug of abuse", analyzed the victim's hair through the Institute of Loyal Medicine in Bonn, which found frequent use of this substance by the victim, at least 4 months before death.The pharmacological effects of exogenous GHB ingestion are dose dependent.
26ock syndrome, spasm and failure of multiple organs.With this analysis performed through scores, it is possible to build estimates designed for the application of practices that improve and speed up the care of lethal cases of intoxication26.The decisive diagnosis is made through blood or urine tests in cases of recent exposure26.In Brazil, in the state of Rio Grande do Norte, a Takifugu poecilonotus and ingested it.After 30 to 60 minutes, he began to experience numbness in his hands and limbs, followed by cyanosis and respiratory failure.Although immediately hospitalized, he died within an hour, and it was con- 31.CD-associated mucosal inflammation can also cause hyponatremia due to reversal of sodium-water flow in the colonic epithelium.Hypernatremia caused by disruption of water homeostasis is a commonly encountered electrolyte disturbance that often progresses to serious complications such as hemorrhage, thrombosis, and cerebral edema, resulting not from the hypernatremia itself, but from its inadequate rate of sodium correction.