Application domain (AD) is crucial for assessing the effectiveness and reliability of model predictions. Common methods for defining the application domain include those based on physicochemical properties, structural features, and biological information. In admetSAR3.0, the AD is defined by ranges of six physicochemical properties, guiding model usage. These properties are molecular weight (MW), logP, number of atoms (nAtom), number of rings (nRing), hydrogen bond acceptors (HBA), and hydrogen bond donors (HBD). We have established a strategy to assess AD by analyzing the distribution of physicochemical properties in the training data. The criteria for the AD are set using the 5th and 95th percentile values of the properties, establishing clear lower and upper boundaries.
The AD assessment classifies results into three categories: "In Domain" "Out Domain" and "Warning". A molecule is labeled "In Domain" if its physicochemical properties entirely fall within the 5th to 95th percentile range. Should any property exceed this range, the molecule receives a "Warning" Moreover, a molecule is tagged "Out Domain" if any of its properties go beyond the maximum or below the minimum values of the training data. Figure 1 illustrates the threshold settings for the applicability domain. Predictions for compounds "In Domain" are deemed reliable and valid. For those marked as "Warning" caution is recommended in using the predictions. Predictions for compounds "Out Domain" are not advisable for reference.
Additionally, we offer the data range for each modeling endpoint, spanning from the minimum to the maximum and from the 5th to the 95th percentile, for user reference. Users can rapidly access information via the interactive introduction feature specific to each endpoint.

MW: Molecular weight. Unit
Result interpretation: The molecular weight of the query molecule is given.

HBA: Number of hydrogen bond donors.
Result interpretation: The number of hydrogen bond donors for the query molecule is given.

HBD: Number of hydrogen bond acceptors.
Result interpretation: The number of hydrogen bond acceptors for the query molecule is given.

TPSA: Topological polar surface area.
Result interpretation: The topological polar surface area for the query molecule is given.

nAtom: Number of atoms.
Result interpretation: The number of atoms for the query molecule is given.

nRing: Number of rings.
Result interpretation: The number of rings for the query molecule is given.

nRot: Number of rotatable bonds.
Result interpretation: The number of rotatable bonds for the query molecule is given.

nHet: Number of heteroatoms.
Result interpretation: The number of heteroatoms for the query molecule is given.

QED: The quantitative estimate of drug-likeness (QED) indicator. The QED was calculated by integrating the output of the desirability function based on eight drug similarity related attributes including MW, log P, HBA, HBD, PSA, nRot, Number of Aromatic Rings (NAr), and Number of Undesirable Functional Group Alarms.
Result interpretation: The QED value for the query molecule is given.

SlogP: The logarithm of the n-octanol/water distribution coefficient. Based on the RDKit calculation. Lipophilicity is a property that can have a significant impact on the ADMET properties as well as the pharmacological activity of a compound.
Result interpretation: The logP value for the query molecule is given.

logP: The logarithm of the n-octanol/water distribution coefficient. Based on the CLMGraph model prediction. Lipophilicity is a property that can have a significant impact on the ADMET properties as well as the pharmacological activity of a compound.
Result interpretation: The logP value for the query molecule is given.

logS: Logarithm of water solubility value. Unit
Result interpretation: The logS value for the query molecule is given.

pKa: The logarithmic acid dissociation constant, pKa, reflects the degree of ionization of a chemical substance, which affects lipophilicity, solubility, protein binding, and ability to pass through the plasma membrane. The pKa reflects the degree of ionization of a chemical substance, which affects lipophilicity, solubility, protein binding and the ability to pass through the plasma membrane. Therefore, pKa affects the ADMET properties of chemicals.
Result interpretation: The pKa value for the query molecule is given.

Lipinski Rule: The rules assess four physicochemical properties
Result interpretation: Accept or Non-accept. Determine if the query molecule has acceptable absorption or permeation properties.

Pfizer Rule: The rule evaluates two physicochemical properties
Result interpretation: Accept or Non-accept. Determine if the query molecule has toxic potential.

GSK Rule: The rule evaluates two physicochemical properties
Result interpretation: Accept or Non-accept. Determine if the query molecule has good potential for ADMET properties.

Caco-2: Caco2 cell permeability. One of the most important challenges facing orally administered drugs is their passage through the intestinal epithelial barrier, which determines the rate and extent of absorption in the body and affects their ultimate bioavailability.The Caco-2 monolayer cell culture model is the "gold standard" for drug permeability and is widely used for prediction of human intestinal permeability in drug discovery.
Result interpretation: The Caco2 cell permeability value for the query molecule is given.

Caco_2_c: Caco2 cell permeability. In this study, the apparent intestinal permeability (Papp) value of 8*10-6 cm/s was used as the threshold value, and when Papp >= 8*10-6 cm/s, it was defined as a high permeability compound; conversely, it was a medium-low permeability compound.
Result interpretation: Determine if the query molecule is a high or low permeability compound.

HIA: Human Intestinal Absorption. Good human intestinal absorption is the primary reason considered for obtaining high oral bioavailability. In experiments, intestinal absorption is usually expressed as a measure of fraction absorption.In this study, a HIA% of 30% was used as the threshold for delineation. Absorption was considered good if HIA% > = 30%; anyway, it was labeled as poor absorption.
Result interpretation: Determine if the query molecule is a well-absorbed or poorly absorbed compound.

MDCK: Madin−Darby Canine Kidney cells (MDCK) Permeability，was utilized as a tool for assessing cell membrane permeability in the early stages of drug development. MDCK cell permeability is one of the more established several in vitro permeability tests that have been developed to mimic in vivo absorption-related characteristics. Apparent permeability (Papp) data was used as an endpoint.In this experiment, 8 * 10-6 cm/s was used as the threshold value, and when Papp >= 8*10-6 cm/s, it was defined as a high transmittance compound; conversely, it was a medium-low transmittance compound.
Result interpretation: Determine if the query molecule is a high or low permeability compound.

F: Oral bioavailability(F). Oral bioavailability is a very important pharmacokinetic parameter, which refers to the speed and degree of entry of a drug into the body circulation after it has been absorbed, and it reflects the proportion of the total dose of a drug that enters the bloodstream in the body circulation. High oral bioavailability and low oral utilization are classified with F= 20%, 30%, and 50% as thresholds, respectively.
Result interpretation: Determine if the query molecule has high oral bioavailability or low oral bioavailability.

BBB: Blood-Brain Barrier Permeability. The blood-brain barrier (BBB) protects the central nervous system (CNS) by separating brain tissue from blood as part of absorption. It is formed mainly by the brain endothelium and prevents the entry of larger (≈100%) and smaller (≈98%) molecules into the CNS, allowing only water- and lipid-soluble molecules and selective transporters to cross itself, while the channel expresses a number of active transporters, such as P-glycoprotein and glucose transporters, preventing the entry of lipophilic potential neurotoxins.
Result interpretation: Determine if the query molecule has better blood-brain barrier permeability.

Transporter-related:Transporters are a class of functional membrane proteins that control the passage of substances in and out of cells and are widely expressed in cells of various organs in the body. As an essential protein in the human body, transporters are important in controlling the uptake of physiologically relevant nutrients, the elimination of foreign substances, and the maintenance of environmental homeostasis in the body. Transporter function has a very important influence on the pharmacokinetic properties and toxicity of drugs.Based on the direction and function of transport, drug transporters can be divided into two categories

OATP1B1 inhibitor: Organic anionic polypeptide 1B1 inhibitor predictor.
Result interpretation: Determine if the query molecule is OATP1B1 inhibitor or non-inhibitor.

OATP2B1 inhibitor: Organic anionic polypeptide 2B1 inhibitor predictor.
Result interpretation: Determine if the query molecule is OATP2B1 inhibitor or non-inhibitor.

OATP1B3 inhibitor: Organic anionic polypeptide 1B3 inhibitor predictor.
Result interpretation: Determine if the query molecule is OATP1B3 inhibitor or non-inhibitor.

OCT1 inhibitor: Organic cation transporter 1 inhibitor predictor.
Result interpretation: Determine if the query molecule is OCT1 inhibitor or non-inhibitor.

OCT2 inhibitor: Organic cation transporter 2 inhibitor predictor.
Result interpretation: Determine if the query molecule is OCT2 inhibitor or non-inhibitor.

BCRP inhibitor: Breast cancer resistant protein inhibitor predictor.
Result interpretation: Determine if the query molecule is BCRP inhibitor or non-inhibitor.

BSEP inhibitor: Bile acid salt efflux pump inhibitor predictor.
Result interpretation: Determine if the query molecule is BSEP inhibitor or non-inhibitor.

MATE1 inhibitor: Multidrug and toxin efflux transporter 1 inhibitor predictor.
Result interpretation: Determine if the query molecule is MATE1 inhibitors or non-inhibitors.

Pgp inhibitor: P-glycoprotein inhibitor predictor.
Result interpretation: Determine if the query molecule is P-gp inhibitor or non-inhibitor.

Pgp substrate: P-glycoprotein substrate predictor.
Result interpretation: Determine if the query molecule is P-gp substrate or non- substrate.

PPB: Plasma protein binding ratio. Plasma protein binding is a very important pharmacokinetic property, which is expressed as the binding affinity of a drug to plasma proteins, and can effectively regulate the effective concentration of a drug at a pharmacological target. When a drug is absorbed by the body into the blood circulation, it selectively binds to plasma proteins. However, only the unbound portion of the drug can reach the specific target and produce therapeutic effects. Therefore, when a drug has a high affinity for plasma proteins, it means that it often requires a higher dose to reach a therapeutic concentration at the target and to exert its effect.
Result interpretation: The predicted result is the plasma protein binding of the compound and the value is a percentage, which refers to the percentage of the drug that is bound to plasma proteins after it has been absorbed by the body into the blood circulation.

VDss: Steady state volume of distribution. Unit
Result interpretation: The VDss value of the query molecule is given.

CYP450-related: Cytochrome P450 enzymes are a superfamily of heme-containing monooxygenases that catalyze the metabolism of a wide range of endogenous and exogenous compounds. It is essential to consider the drug metabolizing role of P450 enzymes in the early stages of drug discovery. Inhibition of cytochrome P450 enzymes is one of the major causes of adverse drug reactions and drug withdrawal. And studies on whether it is a substrate for cytochrome P450 enzymes are also important.

CYP1A2 inhibitor: CYP1A2 inhibitor predictor.
Result interpretation: Determine if the query molecule is CYP1A2 inhibitor or non-inhibitor.

CYP2C9 inhibitor: CYP2C9 inhibitor predictor.
Result interpretation: Determine if the query molecule is CYP2C9 inhibitor or non-inhibitor.

CYP2C19 inhibitor: CYP2C19 inhibitor predictor.
Result interpretation: Determine if the query molecule is CYP2C19 inhibitor or non-inhibitor.

CYP2D6 inhibitor: CYP2D6 inhibitor predictor.
Result interpretation: Determine if the query molecule is CYP2D6 inhibitor or non-inhibitor.

CYP3A4 inhibitor: CYP3A4 inhibitor predictor.
Result interpretation: Determine if the query molecule is CYP3A4 inhibitor or non-inhibitor.

CYP2B6 inhibitor: CYP2B6 inhibitor predictor.
Result interpretation: Determine if the query molecule is CYP2B6 inhibitor or non-inhibitor.

CYP1A2 substrate: CYP1A2 substrate predictor.
Result interpretation: Determine if the query molecule is CYP1A2 substrate or non- substrate.

CYP2C9 substrate: CYP2C9 substrate predictor.
Result interpretation: Determine if the query molecule is CYP2C9 substrate or non- substrate.

CYP2C19 substrate: CYP2C19 substrate predictor.
Result interpretation: Determine if the query molecule is CYP2C19 substrate or non- substrate.

CYP2D6 substrate: CYP2D6 substrate predictor.
Result interpretation: Determine if the query molecule is CYP2D6 substrate or non- substrate.

CYP3A4 substrate: CYP3A4 substrate predictor.
Result interpretation: Determine if the query molecule is CYP3A4 substrate or non- substrate.

CYP2B6 substrate: CYP2B6 substrate predictor.
Result interpretation: Determine if the query molecule is CYP2B6 substrate or non- substrate.

Hepatic metabolic stability: Hepatic metabolic stability is an important pharmacokinetic property that can affect drug clearance, half-life and oral bioavailability in vivo. Characterizing metabolic stability can be used to guide structural modification and optimization of lead compounds. Commonly used models for metabolic stability studies include the hepatic microsomal stability model, the hepatic cellular metabolic stability model, and the hepatic S9 metabolic stability model, of which the hepatic microsomal and hepatic cellular metabolic stability models are the most common. Human and rat liver microsomal stability data were mainly obtained from the ChEMBL database. The half-life = 30 min was used as the threshold value, and compounds with half-life > 30 min were categorized as metabolically stable compounds; compounds with half-life less than or equal to 30 min were categorized as unstable compounds.

HLM: Human liver microsomal stability predictor.
Result interpretation: Determine if the query molecule is metabolically stable compound or a metabolically unstable compound.

RLM: Rat liver microsomal stability predictor.
Result interpretation: Determine if the query molecule is metabolically stable compound or a metabolically unstable compound.

UGT substrate: UGT enzyme substrate predictor.
Result interpretation: Determine if the query molecule is UGT enzyme substrates or non- substrates.

CLp: Plasma clearance is the sum of hepatic and renal and other drug clearance, i.e., how many volumes of plasma are cleared of the drug per unit time, and is an important pharmacokinetic parameter. In this study, the CLp unit was ml/(min*kg), which represents the flow rate. A threshold of 5 ml/(min*kg) was used to divide the compounds into high and low plasma clearance.
Result interpretation: Determine if the query molecule is a high or low plasma clearance.

CLr: Renal Clearance. Renal clearance is the process by which a drug is excreted in its original form through the kidneys in the urine after administration. In this study, a zero threshold was used to determine whether a compound undergoes mainly active secretion or mainly reabsorption during renal clearance
Result interpretation: Determine if the query molecule is a generalized active secretion group or a generalized reabsorption group.

T1/2: Unit
Result interpretation: The half-life of the query molecule is given.

MRT: Unit
Result interpretation: The mean retention time of the query molecule is given.

Neurotoxicity: Neurotoxicity is one of the main reasons for drug discontinuation and there is a need for risk assessment of neurotoxicity of drugs or compounds. Drugs cause neurotoxicity mainly by affecting mitochondrial respiration, immune-mediated responses and inhibiting neuronal activity. Drugs with neurotoxicity can be broadly categorized into three groups, including antibacterials, antifungals, and antidepressants. In addition to drug-induced neurotoxicity, compounds on the industrial market that can cause neurotoxicity are of interest.
Result interpretation: The PLD50 value of the query molecule for producing neurotoxicity is given.

DILI: Drug-induced hepatotoxicity, also known as drug-induced liver injury (DILI), mainly refers to liver damage triggered by the toxic effects of drugs or their metabolites on the organism during clinical use of drugs.
Result interpretation: Determine if the query molecule is a DILI-positive or DILI-negative compound.

Cardiotoxicity: The human ether-a-go-go-related gene (hERG) encodes a tetrameric potassium channel as Kv11.1, which plays an important role in cardiac action potentials. hERG channel inhibition may lead to prolonged QT syndrome (LQTS), which causes avoidable sudden cardiac death. At the same time, adverse hERG-related cardiotoxicity will lead to failure of drug development and is one of the main reasons for drug delisting. half inhibitory concentration (IC50) of hERG channel block is a surrogate marker for compound-induced arrhythmias associated with long LQTS syndrome and cardiac safety testing of the drug or drug candidate.In this study, IC50 of mammals determined by membrane clamp technique was collected as endpoint values and different thresholds were set to categorize the compounds

hERG(1uM): A threshold value of 1 uM was used. compounds with an IC50 greater than 1 uM were considered not to be cardiotoxic, and vice versa for compounds that may cause cardiotoxicity.
Result interpretation: Determine if the query molecule is a hERG-positive or hERG-negative compound.

hERG(10uM): A threshold value of 10 uM was used. compounds with an IC50 greater than 10 uM were considered not to be cardiotoxic, and vice versa for compounds that may cause cardiotoxicity.
Result interpretation: Determine if the query molecule is a hERG-positive or hERG-negative compound.

hERG(30uM): A threshold value of 30 uM was used. compounds with an IC50 greater than 30 uM were considered not to be cardiotoxic, and vice versa for compounds that may cause cardiotoxicity.
Result interpretation: Determine if the query molecule is a hERG-positive or hERG-negative compound.

hERG(<1μM >10μM): Compounds with an IC50 greater than 10uM are considered to be compounds that do not cause cardiotoxicity, and compounds with an IC50 less than 1uM are considered to be compounds that may cause cardiotoxicity.
Result interpretation: Determine if the query molecule is a hERG-positive or hERG-negative compound.

hERG(<10μM >30μM): Compounds with an IC50 greater than 30uM are considered to be compounds that do not cause cardiotoxicity, and compounds with an IC50 less than 10uM are considered to be compounds that may cause cardiotoxicity.
Result interpretation: Determine if the query molecule is a hERG-positive or hERG-negative compound.

Respiratory toxicity: The respiratory system is the most common route for compounds to enter the body, and the lungs are the body's largest organ in contact with the environment. Drugs or environmental compounds that enter the respiratory tract may cause direct damage to the respiratory tract and lungs, in addition to toxic effects on the lungs from drugs that have been absorbed via other routes. The types of toxic effects produced by drugs/compounds on the respiratory system include respiratory depression, respiratory reactions, pulmonary edema, pneumonia, pulmonary fibrosis, pulmonary embolism, pulmonary hemorrhage, and other adverse effects. These toxic effects can cause serious harm and are often not easily diagnosed or detected in the early stages, and early identification of compounds that can cause respiratory toxicity is essential.
Result interpretation: Determine if the query molecule produces respiratory toxicity.

Nephrotoxicity: The kidney is one of the two most important excretory organs in the body. Its basic functions include reabsorption to retain water molecules and other useful substances such as glucose, amino acids, sodium ions, etc., as well as the production of urine to clear the body of certain wastes and toxins. In addition, it regulates the water, electrolyte and acid-base balance of the body's environment. These functions of the kidneys enable metabolism to proceed normally and maintain the stability of the body's internal environment. However, during these processes, the kidneys are usually naturally exposed to drugs and chemicals circulating in the body and are therefore susceptible to damage caused by the effects of the compounds.
Result interpretation: Determine if the query molecule is a DIN-positive or DIN-negative compound.

Eye corrosion: Compounds labeled H314 and H318 were collected as eye corrosion-positive compounds according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).
Result interpretation: Determine if the query molecule has eye corrosive potential.

Eye irritation: H319-labeled compounds were collected as eye irritation-positive compounds according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).
Result interpretation: Determine if the query molecule has eye irritation potential.

Skin corrosion: H314-labeled compounds were collected as skin corrosion-positive compounds according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).
Result interpretation: Determine if the query molecule has skin corrosive potential.

Skin irritation: H315-labeled compounds were collected as skin irritation-positive compounds according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).
Result interpretation: Determine if the query molecule has skin irritation potential.

Skin sensitisation: Skin sensitization is a complex cutaneous immune process caused by local contact of chemical allergens with sensitive skin, often resulting in an inflammatory skin reaction called Allergic Contact Dermatitis (ACD). Due to the prevalence of ACD, skin sensitization has become an important human health indicator that should be considered in chemical hazard and risk assessment. Data for this experiment were obtained from the Murine Local Lymph Node Assay (LLNA) (OECD TG 429). Substances with an induced irritation index greater than or equal to three times the test concentration were classified as skin sensitizers. The degree of skin sensitization of a compound is measured on the basis of its EC3 value, which is the estimated concentration (in g/100 ml) required to produce a threefold irritation index. Compounds are categorized into two groups based on their tested EC3 values
Result interpretation: Determine if the query molecule produce skin sensitization.

Acute dermal toxicity: Acute dermal toxicity refers to the adverse effects of a single administration of a drug that is ingested through the skin of an animal and results in poisoning or even death of the animal, often expressed as the LD50 value, i.e., the lethal dose. It is the smallest dose of a drug required to cause half death of a certain weight or age of a certain drug within a specified period of time and through a specified route of infection. A threshold value of 5000 mg/kg is used, with greater than or equal to 5000 being negative and less than 5000 being positive.
Result interpretation: Determine if the query molecule produce acute dermal toxicity.

Ames mutagenesis: Mutagenicity of compounds is a serious issue that needs to be addressed in early drug development. Currently, the most commonly used in vitro assay for assessing the mutagenic potency of compounds is the bacterial revertant mutation assay, also known as the Ames assay.The main purpose of the Ames assay is to investigate whether compounds have the ability to cause genetic damage as well as base-pair mutations.
Result interpretation: Determine if the query molecule produces Ames mutagenic potential.

Carcinogenicity-related: Carcinogenicity is one of the harmful properties of greatest concern in toxicity studies of compounds. Carcinogenic compounds are compounds that cause tumors or increase the incidence of tumors, which can be a serious hazard to human health. Carcinogenicity data for compounds are measured by the median toxic dose (TD50), which is the dose that causes toxicity (in this case cancer) in 50% of the animals in a toxicity test when the exposure to a substance is sustained over a long period of time. There are three main categories depending on the species tested

Mouse carcinogenicity (c): The test species was mouse and the compounds were evaluated for carcinogenicity.
Result interpretation: Determine if the query molecule produces carcinogenicity potential.

Mouse carcinogenicity: Unit
Result interpretation: The TD50 value of the query molecule for producing carcinogenicity is given.

Rat carcinogenicity (c): The test species was rat and the compounds were evaluated for carcinogenicity.
Result interpretation: Determine if the query molecule produces carcinogenicity potential.

Rat carcinogenicity: Unit
Result interpretation: The TD50 value of the query molecule for producing carcinogenicity is given.

Rodents carcinogenicity: Unit
Result interpretation: Determine if the query molecule produces carcinogenicity potential.

Micronucleus: Genotoxicity testing of new chemical entities is an integral part of the drug development process and is a regulatory requirement prior to approval of new drugs. Genotoxicity is mainly the study of the adverse effects of chemicals on genetic material, and there are many experimental methods commonly used to test the genotoxicity of compounds, such as comet assay, chromosomal aberration assay, bacterial reverse mutation test, bacterial reverse mutation test, micronucleus assay, etc. Among them, in vivo micronucleus assay is a method for detecting toxicity. Among them, in vivo micronucleus assay is a commonly used genotoxicity test method to detect chromosomal damage. The micronucleus assay can detect chemicals that can disrupt the mitotic process and form micronuclei.
Result interpretation: Determine if the query molecule produces genotoxicity potential.

Reproductive toxicity: Among these many safety concerns, reproductive toxicity is one of the main causes of drug withdrawal. Reproductive toxicity not only causes significant damage to the foetus, such as teratogenicity, growth retardation and stunting, but also has a significant impact on the sexual function and reproductive capacity of the offspring. Mechanisms of drug-induced reproductive toxicity include interference with cellular signalling, altered gene expression or oxidative stress.
Result interpretation: Determine if the query molecule produces reproductive toxicity potential.

Mitochondrial toxicity: Mitochondria are important organelles in human cells, providing more than 95% of the energy. However, several drugs and environmental chemicals may induce mitochondrial dysfunction leading to complex diseases. Compounds may affect mitochondrial function through a variety of mechanisms, such as directly affecting mtDNA, inhibiting oxidative phosphorylation, increasing oxidative stress and decreasing mitochondrial inner membrane potential.
Result interpretation: Determine if the query molecule produces mitochondria toxicity potential.

Hemolytic toxicity: The hemolytic toxicity of compounds can cause cell membrane lysis of erythrocytes, allowing hemoglobin to leak into the plasma, which can lead to a variety of side effects, and is one of the important predictive endpoints of toxicity. Compounds with hemolytic toxicity can act directly or indirectly on erythrocytes, affecting osmotic fragility, membrane oxidation, morphology, and ATP energy metabolism of erythrocytes, which in turn can cause rupture of the cell membrane of erythrocytes, resulting in the release of plasma proteins and hemoglobin into plasma, leading to a variety of adverse clinical signs and symptoms.
Result interpretation: Determine if the query molecule produces hemolytic toxicity potential.

Repeated dose toxicity: Repeated dose toxicity studies are a type of toxicology experiments aimed at observing possible toxic reactions in animals after prolonged administration of a drug. This endpoint is an important part of the preclinical toxicology study of a new drug and is an important guide for the subsequent clinical studies conducted. Repeated-dose toxicity is a concept relative to acute toxicity, which is a generalized harmful toxicological effect (excluding reproductive, genotoxic and carcinogenic effects) resulting from repeated daily exposure or contact with a substance at a specific time during the expected lifetime of the test species. This categorization data refer to the GHS requirement to label compounds with a minimum dose level (LOAEL) at which an adverse effect can be observed < 100 mg/kg bw/day as positive and considered to have repeated dose toxicity, and for compounds with a LOAEL of ≥ 100 mg/kg bw/day as negative and considered not to have repeated dose toxicity.
Result interpretation: Determine if the query molecule produces repeated dose toxicity potential.

Acute oral toxicity: Unit

Acute oral toxicity (c): Result interpretation

Acute oral toxicity: Result interpretation

FDAMDD: Unit

FDAMDD (c): A threshold of 0.01 mmol/kg-bw/day was used for categorization.FDAMDD <= 0.01 mmol/kg-bw/day was judged to be positive for FDAMDD; anyway, it was negative for FDAMDD.
Result interpretation: Determine if the query molecule is a high or low FDAMDD compound.

FDAMDD: The regression model then takes -log10 as the FDAMDD endpoint value.
Result interpretation: The FDAMDD predicted value of the query molecule is given.

EDCs-related:The endocrine system plays an important role in the normal operation of the body's generation, development, reproduction and other functions through the regulation of hormone signaling. When certain substances interfere with normal hormone signaling, thus leading to some hormone-regulated dysfunction, this phenomenon is called Endocrine Disruption (ED), and these substances are Endocrine-Disrupting Chemical (EDC), and these substances are endocrine disruptors. Endocrine-Disrupting Chemical (EDC). According to the definition of the World Health Organization, endocrine disruptors are exogenous compounds or mixtures that interfere with normal hormonal functions of the body.

AR: The androgen receptor (AR) is a nuclear hormone receptor that plays a key role in AR-dependent prostate cancer and other androgen-related diseases. Endocrine disrupting chemicals (EDCs) and their interactions with steroid hormone receptors, such as the AR, may lead to disruption of normal endocrine function as well as interference with metabolic homeostasis, reproduction, development, and behavioral function.
Result interpretation: Determine if the query molecule is AR receptor or non-receptor.

ER: Estrogen receptor (ER) is a nuclear hormone receptor that plays an important role in development, metabolic homeostasis and reproduction. Endocrine disrupting chemicals (EDCs) and their interactions with steroid hormone receptors such as ER lead to disruption of normal endocrine function. Therefore, it is important to understand the effects of environmental chemicals on the ER signaling pathway.
Result interpretation: Determine if the query molecule is ER receptor or non-receptor.

AR-LBD: The androgen receptor (AR) is a nuclear hormone receptor that plays a key role in AR-dependent prostate cancer and other androgen-related diseases. Endocrine disrupting chemicals (EDCs) and their interactions with steroid hormone receptors, such as the AR, may lead to disruption of normal endocrine function as well as interference with metabolic homeostasis, reproduction, development, and behavioral function.
Result interpretation: Determine if the query molecule is AR receptor or non-receptor.

ER-LBD: Estrogen receptor (ER) is a nuclear hormone receptor that plays an important role in development, metabolic homeostasis and reproduction. Endocrine disrupting chemicals (EDCs) and their interactions with steroid hormone receptors such as ER lead to disruption of normal endocrine function. Therefore, it is important to understand the effects of environmental chemicals on the ER signaling pathway.
Result interpretation: Determine if the query molecule is ER receptor or non-receptor.

Aromatase: Endocrine disrupting chemicals (EDCs) interfere with the biosynthesis and normal function of steroid hormones, including estrogens and androgens, in the body. Aromatase catalyzes the conversion of androgens to estrogens and plays a key role in maintaining the balance of androgens and estrogens in many EDC-sensitive organs.
Result interpretation: Determine if the query molecule is aromatase receptor or non-receptor.

AhR: The aryl hydrocarbon receptor (AhR) is a member of the basic helix-loop-helix family of transcription factors and is critical for adaptive responses to environmental change.AhR mediates cellular responses to environmental pollutants, such as aromatic hydrocarbons, by inducing phase I and II enzymes, but also interacts with other nuclear receptor signaling pathways.
Result interpretation: Determine if the query molecule is AhR receptor or non-receptor.

ARE: Oxidative stress has been implicated in the pathogenesis of a variety of diseases ranging from cancer to neurodegeneration. The antioxidant response element (ARE) signaling pathway plays an important role in ameliorating oxidative stress.The CellSensor ARE-bla HepG2 cell line (Invitrogen) can be used to analyze the Nrf2/antioxidant response signaling pathway.Nrf2 (NF-E2-related factor 2) and Nrf1 are transcription factors that bind to AREs and activate these Genes.
Result interpretation: Determine if the query molecule affects the ARE.

ATAD5: AAA domain proteins in the ATPase family 5. Since cancer cells divide rapidly, during each cell division they need to replicate their genome through DNA replication. Failure to do so results in the death of the cancer cell. Based on this concept, many chemotherapeutic agents have been developed but have limitations such as low efficacy and high side effects. Enhanced levels of genome destabilizing gene 1 (ELG1; human ATAD5) protein increase in response to various types of DNA damage.
Result interpretation: Determine if the query molecule increases the expression of the ATAD5.

HSE: Heat shock factor response element. Various chemicals, environmental and physiological stress conditions may lead to activation of the heat shock response/unfolded protein response (HSR/UPR). There are three heat shock transcription factors (HSFs) (HSF-1, -2, and -4) that mediate transcriptional regulation of the human HSR.
Result interpretation: Determine if the query molecule affects HSE expression.

p53: p53 is a tumor suppressor protein that is activated following cellular damage, including DNA damage and other cellular stresses. p53 activation regulates cell fate by inducing DNA repair, cell cycle arrest, apoptosis, or cellular senescence. Thus, p53 activation is a good indicator of DNA damage and other cellular stresses.
Result interpretation: Determine if the query molecule affects P53 expression.

PPARγ: Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors of the nuclear receptor superfamily with three distinct isoforms, PPAR alpha, PPAR delta (also known as PPAR beta), and PPAR gamma (PPARg). All of these isoforms heterodimerize with the retinoid X receptor (RXR), and these heterodimers regulate the transcription of a variety of genes.PPAR-gamma receptors (glibenclamide receptors) are involved in the regulation of glucose and lipid metabolism.
Result interpretation: Determine if the query molecule is PPAR or non- PPAR.

MMP: Mitochondrial membrane potential (MMP) is one of the parameters of mitochondrial function and is generated by the mitochondrial electron transport chain, which produces an electrochemical gradient through a series of redox reactions. This gradient drives the synthesis of ATP, a key molecule for various cellular processes. Measurement of MMP in living cells is commonly used to assess the effects of chemicals on mitochondrial function; reductions in MMP can be detected with lipophilic cationic fluorescent dyes.
Result interpretation: Determine if the query molecule affects mitochondrial membrane potential.

TR: Thyroid hormone (TH) is synthesized in the thyroid gland and exists in the form of thyroxine (3,5,3,5-tetraiodothyronine, T4) and triiodothyronine (3,5,3,-triiodothyronine, T3). Of these, T4 is the predominant form of TH present, and T3 is the active form in tissues generated by deiodination of T4. An imbalance in thyroid hormone homeostasis can lead to susceptibility to obesity and cause metabolic disorders. Studies have shown that T3 binds to thyroid hormone receptors (TRs), regulates cellular metabolism and growth and development, and functions in a range of physiological and pathological processes. Therefore, it is of great significance to study TRs and the corresponding regulator molecules.
Result interpretation: Determine if the query molecule affects TR function.

GR: Glucocorticoids are a class of fat-soluble steroid hormones whose secretion is strictly regulated by the hypothalamic-pituitary-adrenal response axis in a circadian rhythm by the zona fasciculata of the adrenal cortex. Glucocorticoids have an extremely important role in maintaining the ecological balance of the organism, participate in the regulation of metabolic homeostasis in the body, and also inhibit the immune response, anti-inflammatory and other effects on all tissues and organs of the organism. In the body, glucocorticoids need to bind to the glucocorticoid receptor distributed in the cell nucleus or cell plasma to exert their physiological or pharmacological effects.
Result interpretation: Determine if the query molecule affects GR function.

Honey bee toxicity: Honey bees (Apis mellifera) are the most important pollinators in natural ecosystems around the globe and are important for crops, forest plants and tropical ecosystems. However, in the last decade, many countries have reported dramatic declines in populations of HBs.HBs are often exposed to pesticides because they help pollinate plants and are sensitive to those pesticides that kill insects. According to the principles of the International Organization for Economic Cooperation and Development (OECD), compounds should be evaluated in experimental tests of acute contact toxicity to honey bees by biostatistics of acute contact toxicity experiments at 24 or 48h to determine the LC50 value or the LD50 value of lethal dose that results in 50% mortality. In this study, a threshold value of 11ug was used and LC50 < 11ug/bee was considered to be acutely toxic to bees on acute exposure and vice versa for compounds that are not acutely toxic to bees on acute exposure.
Result interpretation: Determine if the query molecule produces acute contact toxicity potential.

Avian toxicity: Avian species are extremely sensitive to industrial chemicals and pesticides and are therefore used as model organisms in the field of ecotoxicology to assess chemical toxicity. Avian species are directly exposed to toxic substances through food or skin contact, feather dressing or grooming. Oral ingestion is considered to be the most dominant mode of compound exposure in Avian species. Therefore, oral toxicity testing is one of the major steps in determining the toxic effects of compounds in avian compound toxicity studies. Its testing is usually performed among North American quail (Colinus virginanus) and mallard duck (Anas platyrhynchos).The data in this study are oral toxicity LC50 values for 8-day feeding tests of the subject species. A categorization threshold of 2000 ppm was used, with LC50 > 2000 ppm considered not ornithotoxic to Avian species and LC50 < 2000 ppm considered ornithotoxic to Avian species.

Avain toxicity (Colinus virginanus): The test species was Colinus virginanus and the compounds were evaluated for avain toxicity.
Result interpretation: Determine if the query molecule produces avain toxicity potential.

Avain toxicity (Anas platyrhynchos): The test species was Anas platyrhynchos and the compounds were evaluated for avain toxicity.
Result interpretation: Determine if the query molecule produces avain toxicity potential.

Aquatic toxicity (P. subcapitata): Pseudokirchneriella subcapitata (P. subcapitata) is a standard test alga recommended by QECD for algal toxicity evaluation of compounds. It is a type of green algae, widely distributed in various freshwater aquatic systems, and is one of the most commonly used model organisms for algal toxicity testing.QECD stipulates that the compounds should be tested under the OECD 201 guidelines, and the 72h half growth inhibition rate (EC50) of Pseudohooflagellates subcapitata measured is used as the acute aquatic toxicity data of the compounds. The threshold EC50 = 10 mg/L was used to classify compounds as toxic and non-toxic.
Result interpretation: Determine if the query molecule produces algal aquatic toxicity potential.

Aquatic toxicity (Crustaceans): Chemicals can cause acute aquatic toxicity when they enter waters. Acute aquatic toxicity represents the immediate toxicity caused by an organism through short-term exposure to a chemical. Acute aquatic toxicity is recognized as one of the first parameters that should be considered in chemical risk assessment and screening for priority pollutants. This data is concerned with the aquatic toxicity of compounds to crustaceans in freshwater environments, including the large trevally Daphnia magna, as well as other crustaceans. Locomotor inhibition was used as the endpoint observation, i.e., half effect concentration EC50. with 100 ppm as the threshold, compounds were classified as toxic and non-toxic compounds.
Result interpretation: Determine if the query molecule produces crustacean aquatic toxicity potential.

Aquatic toxicity (D. magna): This data is concerned with the aquatic toxicity of compounds to the crustacean Daphnia magna, a large grebe, in a freshwater environment. Motor inhibition was used as the endpoint observation, i.e., half effect concentration EC50. 100 ppm was used as the threshold to classify the compounds as toxic and non-toxic compounds.
Result interpretation: Determine if the query molecule produces crustacean(Daphnia magna) aquatic toxicity potential.

Aquatic toxicity (Fish): The assessment of identifying chemical hazards to the aquatic environment, i.e., aquatic toxicity, is one of the key components of environmental hazards as well as risk assessment for a wide range of chemicals, and is relevant to the safety of human life. Fish aquatic toxicity is one of the most common endpoints tested to visualize the effects of compounds on aquatic organisms. In this study, LC50 was used as an endpoint and 100 ppm as a threshold to categorize compounds into toxic and non-toxic compounds.
Result interpretation: Determine if the query molecule produces fish aquatic toxicity potential.

Aquatic toxicity (Fathead minnow): The species tested was the Fathead minnow.
Result interpretation: Determine if the query molecule produces fish aquatic toxicity potential.

Aquatic toxicity (Bluegill sunfish): The species tested was the Bluegill sunfish.
Result interpretation: Determine if the query molecule produces fish aquatic toxicity potential.

Aquatic toxicity (Rainbow trout): The species tested was the Rainbow trout.
Result interpretation: Determine if the query molecule produces fish aquatic toxicity potential.

Aquatic toxicity (Sheepshead minnow): The species tested was the Sheepshead minnow.
Result interpretation: Determine if the query molecule produces fish aquatic toxicity potential.

Tetrahymena pyriformis toxicity: Tetrahymena pyriformis, a type of ciliate, is one of the most commonly used biological models in various ecotoxicology experiments and has long been used in aquatic toxicity test assessments. In this study, the negative logarithm of the half growth inhibitory concentration (50% growth inhibitory concentration, IGC50) obtained from the standard TPT test procedure (pIGC50) was used as an index.

Aquatic toxicity (T. pyriformis, c): A pIGC50 = -0.5 was used as the classification threshold. pIGC50 > -0.5 was considered to be toxic to Tetrahymena pyriformis; pIGC50 <= -0.5 was classified as non-TPT.
Result interpretation: Determine if the query molecule is TPT-positive or TPT-negative.

Aquatic toxicity (T. pyriformis): Unit

BCF: The phenomenon in which an organism takes up and accumulates an element or a difficult-to-break-down compound from its surroundings, resulting in a concentration of that substance in the organism that exceeds the concentration in the environment, is called bioconcentration. Bioconcentration is usually expressed in terms of a bioconcentration factor (BCF). BCF is the equilibrium distribution process of chemicals between aquatic organisms and the water body, and the ratio of its (equilibrium) concentration in the organisms to its (equilibrium) concentration in the water body becomes the bioconcentration factor (BCF), which reflects the uptake and storage capacity of aquatic organisms of organic matter in the water body, and it is an important indicator for evaluating the bioaccumulation of organic pollutants. BCF is an indispensable parameter for both the determination of persistent organic pollutants (POPs) and the inventory of persistent bioaccumulative toxic (PBT) pollutants.

BCF (c): Using 1000 L/kg as the classification threshold, compounds with a BCF <1000 were classified as not readily bioconcentrated, and vice versa as readily bioconcentrated.
Result interpretation: Determine if the query molecule produces bioconcentration potential.

BCF: Result interpretation

Biodegradability: Many pesticides and industrial chemicals have been withdrawn from the market because of their persistence, bioaccumulation and toxicity (PBT) properties in the environment.Persisitence is defined as the length of time a substance remains in the environment. A common criterion is its biodegradation half-life in the environment. Biodegradation is the main environmental dissipation process and one of the most important parameters affecting the toxicity, transformation and fate of organic chemicals in aquatic and terrestrial habitats. The data in this study use Biological oxygen demand (BOD) values as endpoint values. If BOD >= 60% of the maximum theoretical oxygen demand, the substance is biodegradable. Otherwise, the substance is considered not readily biodegradable.
Result interpretation: Determine if the query molecule produces biodegradable potential.

Photoinduced toxicity: Photosafety is highly emphasized in drug risk assessment, and drug-induced photosensitized skin reactions are adverse drug reactions of great significance. Photosafety is closely related to molecular photochemistry and photostability properties. Photogenic adverse events are usually categorized as phototoxicity (photoirritation /phototoxicity) or photosensitization (photoallergy), and additionally classified as local or systemic.
Result interpretation: Determine if the query molecule has photoinduced toxicity potential.

Phototoxicity/Photoirritation: Photoirritation /phototoxicity (PIV). Phototoxicity is a dose-dependent phenomenon of drugs and light exposure. Skin reactions vary depending on the sensitizer and its respective intracellular target, with some sensitizers even affecting multiple loci. Erythema is the most common clinical manifestation and can be categorized as immediate, delayed (12-24 hours), or delayed erythema (24-120 hours) depending on onset. Due to its non-immune nature, phototoxicity can only occur in areas of skin exposed to light.
Result interpretation: Determine if the query molecule has phototoxicity potential.

Photoallergy: In a photoallergic reaction (photoallergy, PIH), a photosensitizer absorbs photons and converts them into a bioreactive chromophore. This molecule binds to proteins within the dermis or epidermis to form a complete antigen (semi-antigenization). Thus, a photoallergic reaction is a cell-mediated type IV hypersensitivity reaction that occurs only in previously sensitized patients. An important feature that distinguishes a photoallergic reaction from a phototoxic reaction is the typical "tapering" pattern of skin manifestations, which is typical of delayed hypersensitivity reactions in the skin. This means that in a photoallergic reaction, the skin changes increase during the course of the disease, reaching a peak approximately 48-72 hours after the onset of symptoms (taper pattern).
Result interpretation: Determine if the query molecule produces photoallergic reaction potential.