Herbicides and pesticides synergistically interact at low concentrations in complex mixtures.

Assessing a complex mixture of pesticides at the impacted sites has been challenging for risk assessors for 50 years. The default assumption is that at low concentrations, pesticides interact additively with one another; thus, the risk posed by each component of a complex mixture could be simply added up. The EPA interaction-based hazard index (HIInteraction) modifies this assumption using a binary weight-of-evidence (BINWOE). However, data gaps often preclude HIInteraction use at most sites. This study evaluated these assumptions using the BINWOE to estimate the hazard index (HI) of select pesticide mixtures. The lack of in vivo binary interaction data led us to use a cell line, SH-SY5Y, to obtain the data necessary for the BINWOE approach. In the risk assessment, we considered the most active exposure scenario inhaling a mixture of volatile pesticides from contaminated soil and groundwater. The potential interactions between pesticides in 15 binary mixtures were investigated using the MTT assay in SH-SY5Y cells. Our findings showed that 60% of the binary mixtures elicited synergism (in at least one concentration), 27% displayed antagonism, and 13% showed additive effects in SH-SY5Y cells. Combining human safety data with in vitro interaction data indicated that adults and toddlers were at the highest risk when considering industrial and commercial land use, respectively, compared to other subpopulations. Incorporating interaction data into the risk assessment either increased the risk by up to 20% or decreased the risk by 2%, depending on the mixture. Our results demonstrate the predominant synergistic interactions, even at low concentrations, altered risk characterization at the complex operating site. Most concerning, organochlorine pesticides with the same mechanism of action did not follow dose additivity when evaluated by SH-SY5Y cell lines. Based on our observations, we caution that current HI methods based on additivity assumptions may underestimate the risk of organochlorine mixtures.

Mixture Risk Assessment of Complex Real-Life Mixtures-The PANORAMIX Project.

Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Union's Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising 'real-life' chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for children's development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals.

Liver dysfunction and energy storage mobilization in traíra, Hoplias malabaricus (Teleostei, Erythrinidae) induced by subchronic exposure to toxic cyanobacterial crude extract.

Microcystins (MC) are hepatotoxic for organisms. Liver MC accumulation and structural change are intensely studied, but the functional hepatic enzymes and energy metabolism have received little attention. This study investigated the liver and hepatocyte structures and the activity of key hepatic functional enzymes with emphasis on energetic metabolism changes after subchronic fish exposure to cyanobacterial crude extract (CE) containing MC. The Neotropical erythrinid fish, Hoplias malabaricus, were exposed intraperitoneally to CE containing 100 µg MC-LR eq kg-1 for 30 days and, thereafter, the plasma, liver, and white muscle was sampled for analyses. Liver tissue lost cellular structure organization showing round hepatocytes, hyperemia, and biliary duct obstruction. At the ultrastructural level, the mitochondria and the endoplasmic reticulum exhibited disorganization. Direct and total bilirubin increased in plasma. In the liver, the activity of acid phosphatase (ACP) increased, and the aspartate aminotransferase (AST) decreased; AST increased in plasma. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were unchanged in the liver, muscle, and plasma. Glycogen stores and the energetic metabolites as glucose, lactate, and pyruvate decrease in the liver; pyruvate decreased in plasma and lactate decreased in muscle. Ammonia levels increased and protein concentration decreased in plasma. CE alters liver morphology by causing hepatocyte intracellular disorder, obstructive cholestasis, and dysfunction in the activity of key liver enzymes. The increasing energy demand implies glucose mobilization and metabolic adjustments maintaining protein preservation and lipid recruitment to supply the needs for detoxification allowing fish survival.

Differential neuroprotective effect of curcuminoid formulations in aluminum chloride-induced Alzheimer's disease.

Alzheimer's disease (AD) is a slowly progressive brain degenerative disorder which gradually impairs memory, thinking, and ability to perform easy routine tasks. This degenerative disorder mainly targets the elderly people and has imposed an endemic burden on society. Hence, there is a crucial need to investigate the efficacious herbal pharmacotherapies that can effectively mitigate and prevent the pathological hallmarks of AD. The current study aims to explore the potential efficacy of curcuminoid-rich extract (CRE) and its ternary complex (TC). Experimental rodents were administered with AlCl3 (300 mg/kg) to induce AD and treated with rivastigmine, curcuminoid crude extract, CRE, and TC orally for three consecutive weeks. Neurobehavioral, biochemical, and histopathological studies were performed from the last week of the study period. The mRNA expression of different pathological biomarkers was estimated by RT-qPCR analysis. The results of the study suggested that CRE and TC significantly improved the behavioral, biochemical parameters and acetylcholinesterase inhibitory activity in treatment groups. Histological analysis was also carried out indicating that the neurodegenerative changes and neuronal loss were stabilized by CRE and TC supplementation. CRE and TC supplementation remarkably downregulated the interleukin-1α, tumor necrosis factor-α, interleukin-1ß, acetylcholinesterase, and ß-secretase pathological gene expression. Hence, it was concluded that CRE and TC may act as promising candidates in the prevention of AD via numerous underlying signaling pathways.

Evaluation of interactions in chemical mixtures containing cyanides.

Cyanides are highly toxic chemicals found indoors and outdoors, in air, water, and soil. Environmental exposures often are to mixtures of cyanides with other environmental pollutants. Interactive toxicology is the study of the toxicity of a chemical when it occurs with other chemicals or stressors. Such interactions can modify the joint toxicity of a given mixture. Several binary mixtures of cyanides have been studied in humans and animals to develop antidotes, and their mechanism of action is well understood. We used this limited binary weight of evidence to evaluate the toxicity of untested mixtures, extended it, and applied it to complex environmental mixtures to advance methods for joint toxicity assessment. Federal agencies and local entities provide guidance to evaluate such exposures in the absence of specific data. The objective of this paper is to illustrate use and applicability of ATSDR's framework for evaluation of environmental mixtures, specifically the use of weight of evidence in Tier III, using cyanide mixtures as examples. The results show, for certain cyanide mixtures for which data are available, interactions can be evaluated with a high degree of confidence. For complex mixtures that contain unidentified components, such as found in fires, similarity-based grouping risk assessment is proposed.

Associations of a metal mixture with iron status in U.S. adolescents: Evidence from the National Health and Nutrition Examination Survey.

Iron is needed for normal development in adolescence. Exposure to individual environmental metals (e.g., lead) has been associated with altered iron status in adolescence, but little is known about the cumulative associations of multiple metals with Fe status. We used data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) to examine associations between a metal mixture (lead, manganese, cadmium, selenium) and iron status in 588 U.S. adolescents (12-17 years). We estimated cumulative and interactive associations of the metal mixture with five iron status metrics using Bayesian Kernel Machine Regression (BKMR). Higher concentrations of manganese and cadmium were associated with lower log-transformed ferritin concentrations. Interactions were observed between manganese, cadmium, and lead for ferritin and the transferrin receptor, where iron status tended to be worse at higher concentrations of all metals. These results may reflect competition between environmental metals and iron for cellular uptake. Mixed metal exposures may alter normal iron function, which has implications for adolescent development.

Skin irritation and potential antioxidant, anti-collagenase, and anti-elastase activities of edible insect extracts.

This study aimed to investigate antioxidant, anti-aging, and irritation properties of Thai edible insect extracts, including Bombyx mori, Omphisa fuscidentalis, Euconocephalus sp., Patanga succincta, Acheta domesticus, and Lethocerus indicus. Insects were extracted by 2 different methods, including maceration using ethanol or hexane and digestion using DI water. Then the extracts were determined for protein content using bicinchoninic acid assay and antioxidant activities using 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), 2,2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and ferric thiocyanate assays. Anti-aging activities were investigated by determination of collagenase and elastase inhibitory activities using spectrophotometric assay. Maceration by hexane yielded the highest extract content, whereas aqueous extract from digestion possessed the significantly highest protein content and biological activities (p < 0.05). Interestingly, aqueous extracts of A. domesticus possessed the significantly highest biological activities (p < 0.05) with Trolox equivalent antioxidant capacity value of 8.8 ± 0.1 mmol Trolox/mg, DPPH· inhibition of 19.5 ± 3.8%, equivalent concentration of 12.1 ± 0.7 µM FeSO4/mg, lipid peroxidation inhibition of 31.3 ± 2.4%, collagenase inhibition of 60.8 ± 2.1%, elastase inhibition of 17.0 ± 0.1%, and no irritation effect on chorioallantoic membrane and volunteers. Therefore, aqueous extract of A. domesticus would be suggested for further topical product development.

Evaluation of Acute and Subchronic Toxicity Induced by the Crude Ethanol Extract of Plukenetia volubilis Linneo Leaves in Swiss Albino Mice.

Plukenetia volubilis Linneo (P. volubilis), or Sacha inca, is an oleaginous plant from the Euphorbiaceae family. The presence of terpenoids, saponins, tannins, glycosides, phytosterols, and phenolic compounds in the ethanol extracts of P. volubilis L leaves has been reported, showing a range of bioactivities including antimicrobial, anti-inflammatory, antioxidant, and analgesia. However, the safety of this plant has not yet been reported explicitly. This study thus is aimed at evaluating the toxicity of the ethanol extract of P. volubilis leaves (EtPV) by acute and subchronic toxicity tests in Swiss albino mice following standard procedures set by The Organization for Economic Cooperation and Development (OECD) with slight modifications. In the acute toxicity test, the treatment groups were administered orally with the EtPV at doses of 1000, 3000, 5000, and 7000 mg/kg body weight in small fractions during 16 hours, and the mice were then observed in 14 consecutive days. In the subchronic toxicity study, the EtPV was given at doses of 100, 300, 500, and 700 mg/kg body weight for 90 days. Changes in behavior, mortality rate, and body and the weights of vital organs, hematology, clinical biochemistry, urine analysis, and histologic morphology were evaluated. The acute toxicity study showed that the EtPV causes no sign of toxicity or mortality. The hematological, biochemical and urine analyses, changes in the weight of the body and vital organs (heart, liver and kidney), and histopathological analyses of organs indicated no evidence of toxicity at any doses. It was also revealed that oral administration of EtPV is safe at the oral doses set by acute and subchronic toxicity tests, and the oral lethal dose for the EtPV is higher than 7000 mg/kg. This study is the first to confirm the safety of P. volubilis leaf ethanol extract, and as a result, encouraging further investigation to examine EtPV potential for traditional medicine.

Exploring the utility of the Threshold of Toxicological Concern (TTC) as a screening approach for complex substances.

The Threshold of Toxicological Concern (TTC) has been applied to assess chemical safety for use, particularly in the food safety area. Although the TTC was developed for application to an individual chemical structure, more recently this concept has been suggested for the assessment of combined exposures to multiple chemicals. This study evaluated the potential for applying the TTC to a specific type of co-exposure, that of a complex substance of variable composition which contains multiple constituents, following the World Health Organization/International Programme on Chemical Safety framework for risk assessment of combined exposure to multiple chemicals. The results indicated that the TTC threshold was lower (i.e., more conservative) than regulatory thresholds derived for the same substance or even its most toxic constituent, providing assurance that the TTC could meet the requirements for a conservative screening process. This case study indicates that the TTC concept can be a useful tool to screen for potential risks from complex substances, with the consideration of additional aspects such as variability in chemical constituents and their relative proportions within the substance.

An eight-compound mixture but not corresponding concentrations of individual chemicals induces triglyceride accumulation in human liver cells.

In real life, organisms are exposed to complex mixtures of chemicals at low concentration levels, whereas research on toxicological effects is mostly focused on single compounds at comparably high doses. Mixture effects deviating from the assumption of additivity, especially synergistic effects, are of concern. In an adverse outcome pathway (AOP)-guided manner, we analyzed the accumulation of triglycerides in human HepaRG liver cells by a mixture of eight steatotic chemicals (amiodarone, benzoic acid, cyproconazole, flusilazole, imazalil, prochloraz, propiconazole and tebuconazole), each present below its individual effect concentration at 1-3 µM. Pronounced and significantly enhanced triglyceride accumulation was observed with the mixture, and similar effects were seen at the level of pregnane-X-receptor activation, a molecular initiating event leading to hepatic steatosis. Transcript pattern analysis indicated subtle pro-steatotic changes at low compound concentrations, which did not exert measurable effects on cellular triglycerides. Mathematical modeling of mixture effects indicated potentially more than additive behavior using a model for compounds with similar modes of action. The present data underline the usefulness of AOP-guided in vitro testing for the identification of mixture effects and highlight the need for further research on chemical mixtures and harmonization of data interpretation of mixture effects.

Performance of the GHS Mixtures Equation for Predicting Acute Oral Toxicity.

Acute oral toxicity classifications are based on the estimated chemical dose causing lethality in 50 % of laboratory animals tested (LD50). Given the large number of pesticide registration applications that require acute toxicity data, an alternative to the in vivo test could greatly reduce animal testing. The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Mixtures Equation estimates the acute toxicity of mixtures using the toxicities of mixture components. The goal of this study was to evaluate the concordance of LD50s predicted using the GHS Mixtures Equation and LD50s from the in vivo test results. Using the EPA classification system, concordance was 55 % for the full dataset (N = 671), 52 % for agrochemical formulations (N = 620), and 84 % for antimicrobial cleaning products (N = 51). Most discordant results were from substances LD50 > 2000 mg/kg (limit test) or 2000 < LD50 < 5000 mg/kg that were predicted as LD50 > 5000 mg/kg. A supplementary analysis combining all formulations with an LD50 > 500 mg/kg produced a concordance of 82 %. The lack of more toxic formulations in this dataset prevented a thorough evaluation of the GHS equation for such substances. Accordingly, our results suggest the GHS equation is helpful to predict the toxicity of mixtures, particularly those with lower toxicity.

Chemical interactions and mixtures in public health risk assessment: An analysis of ATSDR's interaction profile database.

The Agency for Toxic Substances and Disease Registry (ATSDR) develops interaction profiles using binary weight of evidence (BINWOE) methodology to determine interaction directions of common environmental mixtures. We collected direction of interactions, BINWOE score determination, and BINWOE score confidence rating from 13 interaction profiles along with toxicodynamic and toxicokinetic influences on interaction direction. By doing so, we quantified the 1) direction of interaction and indeterminate evaluations; 2) characterized confidence in the BINWOE determinations; and 3) quantified toxicokinetic/toxicodynamic, and other influences on projected BINWOE interaction directions. Thirty-nine percent (130/336) of the attempts to make a BINWOE were indeterminate due to no interaction data or inadequate or conflicting evidence. Out of remaining BINWOEs, 25% were additive, 9% were greater-than-additive, and 27% were less-than-additive interactions. Fifty-five percent of BINWOEs were explained by toxicokinetic interactions, 12% and 5% were explained by toxicodynamic and other explanations, respectively. High quality mixture toxicology in vivo studies along with mixture in vitro and in silico studies will lead to greater confidence in interaction directions and influences. Limitations for interpretation of the data were also included.

Developmental toxicity testing of the fume condensate extracts of bitumen and oxidized asphalt in a series of in vitro alternative assays.

The potential developmental toxicity and mode-of-action of fume condensate extracts of bitumen and oxidized asphalt were evaluated in the aryl hydrocarbon receptor (AhR) CALUX assay, the zebrafish embryotoxicity test (ZET), and the mouse embryonic stem cell test (mEST). In the AhR CALUX assay, both fume condensate extracts showed a concentration-dependent AhR induction following 6-h of exposure, but this activity was substantially reduced after 24-h, indicating a transient AhR activation. The main effect observed in the ZET was early embryonic lethality that occurred mostly in the 24 h-post-fertilization (hpf). This typically reflects non-specific toxicity rather than in vitro developmental toxicity of the fume condensate extracts tested since this effect was not seen as a result of the whole cumulative exposure period in the ZET (up to 96 hpf). No malformations were seen in any zebrafish embryo exposed to these fume condensate extracts, although some developed pericardial and/or yolk-sac edemas. Furthermore, both fume condensate extracts tested negative in the mEST. In conclusion, the results show that fume condensate extracts of bitumen and oxidized asphalt do not induce any in vitro developmental toxicity, which is in line with the results observed in the in vivo prenatal developmental toxicity studies performed with the same materials.

Growth Restriction of Rhizoctonia solani via Breakage of Intracellular Organelles Using Crude Extracts of Gallnut and Clove.

Plant diseases reduce crop yield and quality, hampering the development of agriculture. Fungicides, which restrict chemical synthesis in fungi, are the strongest controls for plant diseases. However, the harmful effects on the environment due to continued and uncontrolled utilization of fungicides have become a major challenge in recent years. Plant-sourced fungicides are a class of plant antibacterial substances or compounds that induce plant defenses. They can kill or inhibit the growth of target pathogens efficiently with no or low toxicity, they degrade readily, and do not prompt development of resistance, which has led to their widespread use. In this study, the growth inhibition effect of 24 plant-sourced ethanol extracts on rice sprigs was studied. Ethanol extract of gallnuts and cloves inhibited the growth of bacteria by up to 100%. Indoor toxicity measurement results showed that the gallnut and glove constituents inhibition reached 39.23 µg/mL and 18.82 µg/mL, respectively. Extract treated rice sprigs were dry and wrinkled. Gallnut caused intracellular swelling and breakage of mitochondria, disintegration of nuclei, aggregation of protoplasts, and complete degradation of organelles in hyphae and aggregation of cellular contents. Protection of Rhizoctonia solani viability reached 46.8% for gallnut and 37.88% for clove in water emulsions of 1000 µg/mL gallnut and clove in the presence of 0.1% Tween 80. The protection by gallnut was significantly stronger than that of clove. The data could inform the choice of plant-sourced fungicides for the comprehensive treatment of rice sprig disease. The studied extract effectively protected rice sprigs and could be a suitable alternative to commercially available chemical fungicides. Further optimized field trials are needed to effectively sterilize rice paddies.

Chemical Mixture Calculator - A novel tool for mixture risk assessment.

Humans are continuously exposed to complex chemical mixtures from foods and the environment. Experimental models in vivo and in vitro have increased our knowledge on how we can predict mixture effects. To accommodate a need for tools for efficient mixture risk assessment across different chemical classes and exposure sources, we have developed fit-for-purpose criteria for grouping of chemicals and a web-based tool for mixture risk assessment. The Chemical Mixture Calculator (available at www.chemicalmixturecalculator.dk) can be used for mixture risk assessment or identification of main drivers of risk. The underlying database includes hazard and exposure estimates for more than 200 chemicals in foods and environment. We present a range of cumulative assessment groups for effects on haematological system, kidney, liver, nervous system, developmental and reproductive system, and thyroid. These cumulative assessment groups are useful for grouping of chemicals at several levels of refinement depending on the question addressed. We present a mixture risk assessment case for phthalates, evaluated with and without contributions from other chemicals with similar effects. This case study shows the usefulness of the tool as a starting point for mixture risk assessment by the risk assessor, and emphasizes that solid scientific insight regarding underlying assumptions and uncertainties is crucial for result interpretation.

Pararamosis: Disease of the Rubber Plantations.

Pararamosis is a medical condition, described in the latex extracting areas of the Amazon (rubber tree regions), resulting from contact with the caterpillar of the Premolis semirufa moth. The disease can present itself in an acute form-similarly to other erucisms (injuries caused by moth larvae in humans)-or in a chronic form, typically characterized by the occurrence of changes in the joints of the hands. Because of its importance, in the context of tropical diseases, the objective of this article was to review the main facets of the disease, emphasizing the different pathogenic aspects of the interaction between the arthropod and man.

Mutagenicity and genotoxicity assessments of some industrially processed meat products in Algeria.

Processed meat products are presumptive sources of mutagens and genotoxins for consumers. Several epidemiological studies have reported that these products' high intakes have a positive link with cancer incidence. In Algeria, industrially processed meat products are widely consumed. However, there are no earlier studies involving their genotoxic activity. For this end, the current study aimed at evaluating the mutagenicity and the genotoxicity of some representative industrially processed meat products sold in popular supermarkets. All samples were extracted by established method, using both polar and non-polar solvents. The meat extracts mutagenicity was assessed by Ames test, using four strains of Salmonella typhimurium in the presence and absence of metabolic activation, and subsequently by treat and wash assay for extracts showing biologically significant results. The genotoxicity was determined in TK6 human lymphoblastoid cells using the in vitro micronucleus assay in micromethod. The results showed that all extracts analyzed induce no mutagenic activity. However, one of these extracts induced a biologically significant increase in the number of micronucleated cells. Our findings indicate the importance of the genetic damage detection for taking measures to suppress or reduce the exposure to harmful contaminants and encourage further research investigating genotoxic effects of industrially processed meat worldwide.

Cicadidae Periostracum Attenuates Atopic Dermatitis Symptoms and Pathology via the Regulation of NLRP3 Inflammasome Activation.

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease of complex etiology. Despite its increasing prevalence, treatment for AD is still limited. Crude drugs, including herbal extracts or natural resources, are being used to treat AD symptoms, with minimum side effects. Cicadidae Periostracum (CP), derived from the slough of insects belonging to the family Cicadidae, is a commonly used crude drug in traditional Asian medicine to treat/control epilepsy, shock, and edema. However, the effect of CP on AD-like skin lesions is unknown. In this study, we examined the effect of a CP water extract on AD disease development in vivo, using a house dust mite-induced AD mouse model, and in vitro, using HaCaT keratinocytes and a 3D human skin equivalent system. Importantly, CP administration alleviated house dust mite-induced AD-like symptoms, suggested by the quantified dermatitis scores, animal scratching behaviors, skin moisture retention capacity, and skin lesion and ear thickness. Furthermore, histopathological analysis demonstrated that CP decreased intralesional mast cell infiltration. In addition, CP treatments decreased the systemic levels of immunoglobulin E, histamine, and thymic stromal lymphopoietin (TSLP) and the local mRNA expression of TSLP and several Th1/Th2 cytokines. Our data suggest that these effects were mediated by the inhibition of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation. In vivo and in vitro CP treatments resulted in the downregulation of inflammasome components, such as ASC and cleaved caspase-1, as well as related mediators such as IL-1ß and reactive oxygen species. Collectively, our results suggest that CP is a potential therapeutic agent for AD, controlling inflammatory responses through the suppression of NLRP3 inflammasome activation.

Acaricidal activity of Furcraea foetida leaf extract against engorged female Rhipicephalus (Boophilus) microplus ticks

The Rhipicephalus (Boophilus) microplus tick is a major concern for the livestock market worldwide, as it causes serious economic damage. Plant-derived acaricides are an attractive alternative to control this ectoparasite and limit the development of resistance. Therefore, the aim of this study was to evaluate the acaricidal activity of Furcraea foetida leaf extract against engorged female R. (B.) microplus ticks. Our in vitro bioassays showed that the crude extract of leaves from F. foetida caused hemorrhagic swelling and skin lesions in the ticks, and three days of treatment caused 100% mortality. Dose-response assay indicated that this toxicity effect was dose-dependent. Similar effects were observed when the crude extract from F. foetida leaves was denatured by boiling at 100°C. These results suggest that the toxicity of the leaf extract might be associated with thermostable biomolecules. Together, our results show for the first time that the crude extract of F. foetida leaves has acaricidal activity against engorged female R. (B.) microplus ticks and it acts in a dose-dependent manner.

Sub-acute oral toxicity study of aqueous extract of tobacco leaves (Nicotiana tabacum L.) on lipid profile, the tissue, and serum of the liver and kidney of male Wistar rats.

CONTEXT: Tobacco consumption may pose a very serious threat to the physiological state of the body; yet, fewer records have been documented in that regard. OBJECTIVE: We investigated the impact of aqueous extract of tobacco leaves on the lipid profile, the tissue, and serum levels of the liver and kidney of male Wister rats. MATERIALS AND METHODS: Rats (n = 52; weight = 33 - 47 g; ∼ 2½ weeks old) were acclimatised for 7 days and administered aqueous extract of tobacco leaves at 100, 200, 400, 0 mg/kg of body weight (to group A, B, C, D) for 30 days. RESULTS: Compared with the control group, the kidney tissue and serum (i.e., urea and creatinine) were not influenced, in contrast, indices of the liver such as AST, ALT, and ALP, dose-dependently increased. Changes such as coagulative necrosis resulted in the infiltration of mononuclear inflammatory cells and the vacuolar degeneration of the liver. Beside the reduction in the high-density lipoprotein of the rats, there was an increase in the concentration of triglycerides, very low-density lipoprotein, low-density lipoprotein, and the total cholesterol. CONCLUSION: Thus, extract of tobacco leaves can greatly influence the body lipid profile, beside the serum and tissues of the liver.