DNA topoisomerase II “poisons (interferes with) topo II enzyme ; MLL chromosomal translocation ; Infant leukaemia ; DNA double-strand break

Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) ; Increased, valve movement ; Increased, serotonin (5-HT) ; Increased, oocyte maturation ; induced spawning ; Increased, Reproductive Success ; Increase, cilia movement ; Increased, Population

Increased, predation ; Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) ; Increased, serotonin (5-HT) ; Decreased, anxiety ; Decreased, sheltering

Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) ; Increased, muscular waves in foot ; Increased, water retention in foot ; Increased, valve movement ; Depletion, energy reserves ; Increased, foot detachment ; Increased, locomotion ; Increased, serotonin (5-HT) ; Increase, predation ; Decline, Population

Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) ; Increased, valve movement ; Increased, serotonin (5-HT) ; Decline, Population ; Increase, cilia movement ; increased mantel display ; Induced parturition ; Decreased, Reproductive Success

Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) ; Increased, valve movement ; Increased, serotonin (5-HT) ; Increased, Reproductive Success ; Increase, cilia movement ; Increased, Population ; increased mantel display ; Induced parturition

Death/Failure, Colony ; Abnormal, Roll change within caste ; Reduced, Brood care ; impaired, Larval development

Increased, Mortality ; Inhibition, Acetylcholinesterase (AchE) ; Accumulation, Acetylcholine in synapses ; Increased, Atrioventricular block and bradycardia ; Increased, Respiratory distress/arrest ; Induction, Ataxia, paralysis, or hyperactivity ; Decreased, Population trajectory

AChE binding ; Seizures ; Death ; Decreased AChE in neurons ; Increased residence time of AChE ; Loss of consciousness ; Headache and fatigue ; Signaling disruption ; Convolutions ; Tremors ; Paralysis ; Population reduction

Peptide Oxidation ; Reproductive failure ; Activation, JNK ; Activation, FOXO ; Inhibition, Wnt pathway ; Defect of Embryogenesis

Formation, Pro-mutagenic DNA Adducts ; Increased, Induced Mutations in Critical Genes ; Metabolism of AFB1, Production of Reactive Electrophiles ; Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) ; Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts ; Tumorigenesis, Hepatocellular carcinoma

Activation, AHR ; Up Regulation, CD36 ; Accumulation, Triglyceride ; Accumulation, Fatty acid ; Suppression, VLDL secretion ; Inhibition, Mitochondrial fatty acid beta-oxidation ; Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) ; Increased, SCD-1 ; Increased, FA Influx ; Up Regulation, LDLR (low density lipoprotein receptor) ; Increased, LDL uptake ; Up Regulation, CYP1A1 ; Accumulation, Liver lipid ; Up Regulation, SCD-1

Activation, SREBF1 ; Increased, Liver Steatosis ; systemic inflammation leading to hepatic steatosis ; Activation, AKT2 ; Activtation, SREBP-1c

Alkylation, DNA ; Increase, Mutations ; N/A, Insufficient or incorrect DNA repair ; Increase, Heritable mutations in offspring

Alkylation, DNA ; Increase, Mutations ; N/A, Insufficient or incorrect DNA repair ; Increase, Cancer

Increased, Binding of chemicals to 2u (serum) ; Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) ; Increase, Cytotoxicity (renal tubular cell) ; Increase, Regenerative cell proliferation (tubular epithelial cells) ; Increase, Hyperplasia (renal tubular cells) ; Increase, Adenomas/carcinomas (renal tubular)

Decreased, GnRH cfos activity ; Decreased, GnRH pulsatility/release ; Decreased, LH Surge ; Delayed, Ovulation ; Decreased, Cortical granule release/distribution upon fertilization ; Altered, Formation of cortical envelope ; Abnormal, Sperm penetration (polyspermy) ; Altered, Chromosome number (polyploid) zygote ; Decreased, Decreased fecundity ; Inhibition, Antgonism of NE receptor ; Decreased, Binding of NE to NE receptors on GnRH neurons

Increased, Mortality ; impaired, ion channels ; Altered, Action Potential ; Increased, cardiac arrthymia

Increase, Mitogenic cell proliferation (hepatocytes) ; Increase, Adenomas/carcinomas (hepatocellular) ; Increase, Preneoplastic foci (hepatocytes) ; Activation, Androgen receptor

Androgen receptor, agonism ; Gonadotropins, circulating concentrations, reduction ; Testosterone synthesis by ovarian theca cells, reduction ; 17beta-estradiol synthesis by ovarian granulosa cells, reduction

Reduction, Plasma 17beta-estradiol concentrations ; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells ; Agonism, Androgen receptor ; Reduction, Testosterone synthesis by ovarian theca cells ; Reduction, Vitellogenin synthesis in liver ; Reduction, Cumulative fecundity and spawning ; Reduction, Plasma vitellogenin concentrations ; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development ; Reduction, Gonadotropins, circulating concentrations ; Decrease, Population trajectory

N/A, Androgen receptor, Antagonism ; Alteration, Wnt pathway ; Feminisation or incomplete development, Primary and accessory male sex organs ; Decreased, Transcription of genes by AR ; N/A, Impairment of reproductive capacity

Antagonism of the androgen receptor ; Decrease in transcription of androgen dependent genes ; Repression of Wnt signalling ; Alteration of cell proliferation and differentiation of androgen dependent organs ; Developmental toxicity by antagonism of the androgen receptor

Binding of antagonist, PPAR alpha ; Decreased, PPARalpha transactivation of gene expression ; Decreased, Mitochondrial Fatty Acid Beta Oxidation ; Decreased, Ketogenesis (production of ketone bodies) ; Not Increased, Circulating Ketone Bodies ; Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids ; Increased, Catabolism of Muscle Protein ; stabilization, PPAR alpha co-repressor ; Decreased, Body Weight ; Fatty Acid Beta Oxidation, Decreased

Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone ; Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP ; Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin ; Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis ; Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) ; Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) ; Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal ; Hemostasis, Depletion from blood of fully functional carboxylated clotting factors ; Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction ; Osteoporosis and vascular calcification, Bone deterioration ; Impaired recruitment , Population trajectory

Increased, latency period ; Increased, Adenomas/carcinomas (mammary) ; Decreased, Dopaminergic activity ; Increased, prolactin secretion ; Increased, hyperplasia (mammary gland)

Decreased, Ovarian E2 ; Suppression, Estrogen receptor (ER) activity ; Increased, secretion of GnRH from hypothalamus ; Increased, secrection of FSH from anterior pituitary ; Increased, secretion of LH from anterior pituitary ; Hyperplasia, ovarian stromal cells ; Hyperplasia, ovarian epithelium ; Decrease, E2 blood concentrations at hypothalamus ; Promotion, ovarian adenomas ; Promotion, ovarian granular cell tumors

Decompartmentalization ; Direct mitochondrial inhibition ; narcosis ; Mitochondrial impairment ; Apoptosis ; Necrosis

reduction in ovarian granulosa cells, Aromatase (Cyp19a1) ; Reduction, Plasma 17beta-estradiol concentrations ; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells ; impaired, Fertility ; irregularities, ovarian cycle

Inhibition of the aromatase enzyme ; Decrease in conversion of testosterone to oestradiol ; Decrease in transcription of oestrogen receptor genes ; Developmental toxicity by inhibition of the aromatase enzyme with letrozole

Inhibition of Aromatase Enzyme, Chemical exposure during critical window of estrous cycle between diestrus 2 and proestrus inhibits aromatase conversion of testosterone to estradiol ; reduction in ovarian granulosa cells synthesis of estradiol, Reduced steroidogenic production of estradiol in granulosa cells ; Reduced Estradiol in Circulation, Reduced steroidogenic production of estradiol in granulosa cells leading to decreased estradiol in circulation ; Decreased positive estrogenic feedback on hypothalamus, Reduced estradiol in circulation decreases estrogen concentration at hypothalamus ; Decreased Kisspeptin release from neurons in AVPV, Decreased hypothalamic estrogen reduces kisspeptinergic neuron response ; Decreased GnRH Release, Decreased Kisspeptin stimulation of GnRH neurons ; Decreased LH release from Anterior Pituitary, Decreased GnRH stimulation of Anterior Pituitary Gonadotrophs ; Ovulation of oocytes Reduced, Delayed, or Blocked, Decrease or delay in LH surge required for ovulation ; Decreased fertility, Reduced number of oocytes ovulated

Reduction, Plasma 17beta-estradiol concentrations ; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells ; Reduction, Vitellogenin synthesis in liver ; Reduction, Cumulative fecundity and spawning ; Reduction, Plasma vitellogenin concentrations ; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development ; Decrease, Population trajectory ; Inhibition, Aromatase

Increased, Mortality ; Decreased, Population trajectory ; Activation, AHR ; dimerization, AHR/ARNT ; Increase, COX-2 expression ; Altered, Cardiovascular development/function ; Increase, Mortality ; Increase, Early Life Stage Mortality

Activation, AHR ; dimerization, AHR/ARNT ; Altered, Cardiovascular development/function ; Impairment, Endothelial network ; reduced dimerization, ARNT/HIF1-alpha ; Increase, Pericardial edema ; reduced production, VEGF ; Increase, Early Life Stage Mortality

Activation, AHR ; Oxidation, Uroporphyrinogen ; Inhibition, UROD ; Accumulation, Highly carboxylated porphyrins ; Induction, CYP1A2/CYP1A5 ; Uroporphyria

Increased, Mortality ; modulation, sodium channel ; prolonged, Depolarization of neuronal membrane ; Overactivation, Neuronotransmitter release ; Overactivation, muscle contraction ; Increased, Ataxia, paralysis, or hyperactivity

Activation, beta-2 adrenergic receptor ; Increased activity, beta-2 adrenergic receptor ; relaxation, smooth muscle ; Proliferation/Clonal Expansion, smooth muscle ; Hypertrophy/hyperplasia, smooth muscle ; Promotion, mesovarian leiomyomas

N/A, Mitochondrial dysfunction 1 ; N/A, Neuroinflammation ; N/A, Cell injury/death ; N/A, Neurodegeneration ; Impairment, Learning and memory ; Binding of agonist, Ionotropic glutamate receptors ; Overactivation, NMDARs ; Increased, Intracellular Calcium overload ; Decreased, Neuronal network function in adult brain

N/A, Mitochondrial dysfunction 1 ; N/A, Neuroinflammation ; N/A, Cell injury/death ; N/A, Neurodegeneration ; Impairment, Learning and memory ; Decrease of neuronal network function ; Binding, SH-/selen-proteins ; N/A, Interferences with SH-/selen-proteins ; Depletion, GSH ; N/A, Oxidative stress ; N/A, Neuronal dysfunction ; Oxidative Stress ; Binding, Thiol/seleno-proteins involved in protection against oxidative stress ; Glutamate dyshomeostasis ; Tissue resident cell activation ; Increased Pro-inflammatory mediators ; Decreased protection against oxidative stress

Binding of nicotine to nicotinic receptors alpha4Beta2 and alpha7 (agonism) ; Activation of Voltage operated calcium channels (pre-synaptic) and direct depolarisation (post-synaptic) ; Alteration of neurotrasmitter release such as dopamine, norepinephrine, serotonin ; Apoptosis ; Nicotine exposure developmental outcome

Binding of nicotine to nicotinic receptors alpha4Beta2 and alpha7 (agonism) ; Activation of Voltage operated calcium channels (pre-synaptic) and direct depolarisation (post-synaptic) ; Alteration of neurotrasmitter release such as dopamine, norepinephrine, serotonin ; Apoptosis ; Nicotine exposure developmental outcome

Binding at picrotoxin site, iGABAR chloride channel ; Reduction, Ionotropic GABA receptor chloride channel conductance ; Occurrence, A paroxysmal depolarizing shift ; Reduction, Neuronal synaptic inhibition ; Generation, Amplified excitatory postsynaptic potential (EPSP) ; Occurrence, Epileptic seizure

Binding to Thyroid Peroxidase (TPO) ; Decreased levels of TPO ; Decrease levels of serum T4 and T3 ; Altered TR mediated proteints ; Synaptic malformation and altered function ; Learning impairment

Inhibition, Ca++ ATPase ; Increase, Ca++ (intracellular) ; Disruption, Mitochondrial electron transport chain ; Decrease, Mitochondrial ATP production ; Increase, Reactive oxygen species production ; Decreased, Nitric Oxide ; Decreased, Long-term potentiation (LTP) ; Increased, Oxidative damage

Binding, Tubulin ; Depolymerization, Microtubule ; Disorganization, Spindle ; Altered, Meiotic chromosome dynamics ; Altered, Chromosome number ; Increase, Aneuploid offspring

Increase, Mortality ; Increase, Chitin synthase inhibition ; Decrease, Cuticular chitin synthesis ; Increase, Premature molting

Inhibition, Bile Salt Export Pump (ABCB11) ; Activation of specific nuclear receptors, Transcriptional change ; Bile accumulation, Pathological condition ; Release, Cytokine ; Increase, Inflammation ; Production, Reactive oxygen species ; Peptide Oxidation ; Cholestasis, Pathology

Binding of antagonist, NMDA receptors ; Inhibition, NMDARs ; Decreased, Calcium influx ; Reduced levels of BDNF ; N/A, Cell injury/death ; Impairment, Learning and memory ; Aberrant, Dendritic morphology ; Decrease of synaptogenesis ; Decrease of neuronal network function ; Reduced, Presynaptic release of glutamate

NMDARs, Binding of antagonist ; NMDARs, Inhibition ; Calcium influx, Decreased ; Release of BDNF, Reduced ; Presynaptic release of glutamate, Reduced ; Cell death, N/A ; Dendritic morphology, Aberrant ; Synaptogenesis, Decreased ; Neuronal network function, Decreased ; Learning and memory, Impairment

N/A, Neuroinflammation ; Binding of antagonist, NMDA receptors ; Inhibition, NMDARs ; Decreased, Calcium influx ; Reduced levels of BDNF ; N/A, Cell injury/death ; N/A, Neurodegeneration ; Impairment, Learning and memory

Activation of Cyp2E1 in the liver ; Oxidative Stress ; Hepatocytotoxicity ; Hepatocellular Regenerative Proliferation ; Liver Cancer

Increase, Adenomas/carcinomas (hepatocellular) ; Increase, Preneoplastic foci (hepatocytes) ; Increase, Cytotoxicity (hepatocytes) ; Increase, Regenerative cell proliferation (hepatocytes)

Increased, Oxidative Stress ; Increased, secretion of local growth factors ; persistent, cytotoxicity (pleura or peritoneum) ; Increased, inflammation ; Increased, Cell Proliferation (mesothelium) ; Increased, mesotheliomas

Increase, Mitogenic cell proliferation (hepatocytes) ; Increase, Adenomas/carcinomas (hepatocellular) ; Activation, Constitutive androstane receptor ; Altered gene expression specific to CAR activation, Hepatocytes ; Increase, Preneoplastic foci (hepatocytes)

Covalent Binding, Protein ; Activation, Keratinocytes ; Activation, Dendritic Cells ; Activation/Proliferation, T-cells ; sensitisation, skin

Increased, Mortality ; Decline, Population ; Increased, blood uric acid concentration ; Occurrence, renal proximal tubular necrosis ; Increased, blood potassium concentration ; Occurrence, tophi (urate) deposition ; Occurrence, cardiac arrhythmia ; Increased, Oxidative Stress ; Inhibition, Cyclooxygenase 1 activity ; Decreased, Prostaglandin F2alpha concentration, plasma ; Occurrence, renal ischemia

Inhibition, Cyclooxygenase activity ; Reduction, Prostaglandin E2 concentration ; Reduction, Ca and HCO3 transport to shell gland ; Reduction, Eggshell thickness ; N/A, Gap ; N/A, Reproductive failure

Decrease, Population trajectory ; Inhibition, Cyclooxygenase activity ; Decrease, Ovulation ; Reduced, Prostaglandins, ovary ; Reduced, Reproductive Success ; Declining, Population trajectory

Decrease, Population trajectory ; Inhibition, Cyclooxygenase activity ; Reduced, Reproductive Success ; Reduced, Prostaglandin F2alpha concentration, plasma ; Reduced, Prostaglandin F2alpha synthesis, ovary ; Reduced, Spawning behavior ; Reduced, Ability to attract spawning mates

Decrease, Population trajectory ; Inhibition, Cyclooxygenase activity ; Reduced, Reproductive Success ; Reduced, Prostaglandin F2alpha concentration, plasma ; Reduced, Ability to attract spawning mates ; Reduced, Pheromone release ; Decreased, Prostaglandin F2alpha synthesis, ovary ; Decline, Population trajectory

Decrease, Population trajectory ; Inhibition, Cyclooxygenase activity ; Reduced, Reproductive Success ; Decline, Population trajectory ; Reduced, Prostaglandin E2 concentration, hypothalamus ; Reduced, Gonadotropin releasing hormone, hypothalamus ; Reduced, Luteinizing hormone (LH), plasma ; Reduced, Maturation inducing steroid, plasma ; Reduced, Maturation inducing steroid receptor signalling, oocyte ; Reduced, Meiotic prophase I/metaphase I transition, oocyte ; Increased, cyclic adenosine monophosphate

Decrease, Population trajectory ; Inhibition, Cyclooxygenase activity ; Reduced, Reproductive Success ; Declining, Population trajectory ; Reduced, Prostaglandin E2 concentration, hypothalamus ; Reduced, Gonadotropin releasing hormone, hypothalamus ; Reduced, Luteinizing hormone (LH), plasma ; Reduced, Maturation inducing steroid, plasma ; Reduced, Maturation inducing steroid receptor signalling, oocyte ; Upregulated, Spindle assembly checkpoint protein Mad2-oocyte ; Increased, Chromosome misseggregation

CYP2E1 Activation ; Protein Adduct Formation ; Oxidative Stress in Brain ; Lipid Peroxidation ; Unfolded Protein Response ; General Apoptosis ; Neurodegeneration

Increase, Cytotoxicity (club cells) ; Increase, Necrosis (terminal bronchiolar cells) ; Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells) ; Increase, Hyperplasia (terminal bronchiolar cells) ; Increase, Adenomas/carcinomas (bronchioloalveolar)

Increase, Regenerative cell proliferation (tubular epithelial cells) ; Increase, Adenomas/carcinomas (renal tubular) ; Increase, Cytotoxicity (tubular epithelial cells) ; Increase, Hyperplasia (tubular epithelial cells)

Increase, DNA damage ; Increase, Excessive reactive oxygen species generation ; Increase, Apoptosis ; Increase, D1 protein blockage ; Decrease, Photosystem II activity ; Decrease, Growth

Decrease, Mitochondrial ATP production ; Decrease, Photosynthesis ; Decrease, Glycolysis ; Increase, D1 protein blockage ; Decrease, Photosystem II activity ; Decrease, Growth

Death/Failure, Colony ; Abnormal, Roll change within caste ; impaired, Larval development ; Decreased, Glucose oxidase enzyme activity ; Decreased, Hydrogen peroxide production ; Reduced, Antiseptic incorporated in food ; Reduced, Food storage

Decreased, Androgen receptor activity ; Decreased, Testosterone binding to androgen receptor (hypothalamus) ; Increase, Hyperplasia (Leydig cells) ; Increased, Luteinizing hormone (LH) ; Increase, Leydig cell tumors

Decrease, Population trajectory ; Decreased, Triiodothyronine (T3) in serum ; Reduced, Swimming performance ; Reduced, Young of year survival ; Reduced, Anterior swim bladder inflation ; Reduced, Hearing ; Inhibition, Deiodinase 1

Decrease, Population trajectory ; Decreased, Triiodothyronine (T3) in serum ; Reduced, Posterior swim bladder inflation ; Reduced, Swimming performance ; Reduced, Young of year survival ; Reduced, Anterior swim bladder inflation ; Reduced, Hearing ; Inhibition, Deiodinase 1

Decrease, Population trajectory ; Inhibition, Deiodinase 2 ; Decreased, Triiodothyronine (T3) in serum ; Reduced, Swimming performance ; Reduced, Young of year survival ; Reduced, Anterior swim bladder inflation ; Reduced, Hearing

Decrease, Population trajectory ; Inhibition, Deiodinase 2 ; Decreased, Triiodothyronine (T3) in serum ; Reduced, Posterior swim bladder inflation ; Reduced, Swimming performance ; Reduced, Young of year survival ; Reduced, Anterior swim bladder inflation ; Reduced, Hearing

Inhibition, VegfR2 ; Reduction, Angiogenesis ; Impairment, Endothelial network ; Insufficiency, Vascular ; Increased, Developmental Defects

Intercalation with Nuclear and mt DNA ; Heart Failure ; Respiratory Failure ; Inhibition of Topoisomerase II ; Altered Expression of ETC Proteins ; Deregulation and Increase of mt Calcium Loading ; Reduced Calcium Loading Capacity of Mitochondria ; Calcium-Induced MPT ; Inhibited DNA Replication ; Altered Sychronization of Calcium in Myocytes ; Calcium-Induced Cell Death in Myocytes ; Altered Calicium Signaling ; Tumor Cell Death and Regression ; Congestive Heart Failure ; Increased Sensitivity to Calcium Loading/ROS in Myocytes ; Dialated CardioMyopathy ; Accumulating Risk for Cardiopathy

Thyroid hormone synthesis, Decreased ; Decreased, Thyroxine (T4) in serum ; Decreased, Thyroxine (T4) in tissues ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis ; Inhibition, Dual oxidase

prepubertal increase, Estrogen receptor (ER) activity ; Activation, estrogen receptor alpha ; Promotion, SIX-1 postive basal-type progenitor cells ; Proliferation/Clonal Expansion, aberrant basal cells ; squamous metaplasia, aberrant basal cells ; Increased, Hyperplasia (glandular epithelial cells of endometrium) ; Increased, adenosquamous carcinomas of endometrium

Increase, Ecdysone receptor agonism ; Increase, Nuclear receptor E75b gene expression ; Increase, Fushi tarazu factor-1 gene expression ; Decrease, Circulating ecdysis triggering hormone ; Decrease, Circulating crustacean cardioactive peptide ; Decrease, Ecdysis motoneuron bursts ; Decrease, Excitatory postsynaptic potential ; Decrease, Abdominal muscle contraction ; Increase, Incomplete ecdysis ; Increased, Mortality ; Increase, Mortality

Activation, EGFR ; Occurrence, Transdifferentiation of ciliated epithelial cells ; Occurrence, Metaplasia of goblet cells ; Occurrence, Hyperplasia of goblet cells ; Increase, Proliferation of goblet cells ; Activation, SP1 ; Decrease, Apoptosis of ciliated epithelial cells ; Increase, Mucin production ; Chronic, Mucus hypersecretion ; Decrease, Lung function

Increased, induction of UDPGT's in liver ; Increased, T4/T3 catabolism ; Decreased, serum T4/T3 ; Increased, Thyroid-stimulating hormone (TSH) ; Increased, Hypertrophy and proliferation (follicular cell) ; Increased, Hyperplasia (follicular cells) ; Increased Apoptosis, Adenomas/carcinomas (follicular cell)

peroxisome proliferator activated receptor promoter demethylation ; Activation of specific nuclear receptors, PPAR-gamma activation ; chronic high fat diet ; activation of CCAAT/enhancer-binding protein alpha ; increased adipogenesis ; decreased dopamine ; decreased reward ; decreased DNA methylation of tyrosine hydroxylase ; decreased methylation of dopamine transporter promoter ; obesity

Increase, Inflammation ; Increase, Papillomas/carcinomas (squamous cells) ; Increase, Cytotoxicity (epithelial cells) ; Increase, Regenerative cell proliferation (forestomach epithelial cells) ; Increase, Hyperplasia (forestomach epithelial cells)

Agonism, Estrogen receptor ; Increase, Plasma vitellogenin concentrations ; Increased, Vitellogenin synthesis ; Increased, renal vitellogenin deposition ; Increased, glomerular rupture and renal hemorrhaging ; Increased, nephropathy

Agonism, Estrogen receptor ; skewed, sex ratio

Binding to ER ; ER Transcription Factors ; Upreregulated Gene Transcription in the liver tissue ; Gene expression for Vtg production ; Alteration of Anal fin papillae ; Alteration of Gonadal morphology ; Reduced Growth ; Reduced eggs per female ; Reduced Fertility ; Mixed sex gonads ; Sex reversal ; Delayed adult mail mortality ; Altered sex ratios ; Population reduction

N/A, Mitochondrial dysfunction 1 ; Increased, Oxidative Stress ; Activation, Estrogen receptor ; Increase, Cell Proliferation (Epithelial Cells) ; Decreased, Apoptosis (Epithelial Cells) ; Increased, ER binding to DNA (classical pathway) ; Increased, ER binding to T.F. to DNA (non-classical pathway) ; Increased, Proliferation (Endothelial cells) ; Increased, Migration (Endothelial Cells) ; Increased, Non-genomic signaling ; Increased, Ductal Hyperplasia ; Increase, DNA damage ; modulation, Extracellular Matrix Composition ; Increased, Invasion ; Activation, Fibroblasts ; Activation, Macrophages ; Increased, Angiogenesis ; Altered, Gene Expression ; Altered, Protein Production ; Increased, Motility ; Increased, Second Messenger Production ; N/A, Breast Cancer

Reduction, Cumulative fecundity and spawning ; Decrease, Population trajectory ; Agonism, Estrogen receptor ; Increase, Plasma vitellogenin concentrations ; Increase, Vitellogenin synthesis in liver ; Increase, Renal pathology due to VTG deposition ; Altered, Reproductive behaviour ; Altered, Larval development ; Impaired development of, Reproductive organs

Reduction, Vitellogenin synthesis in liver ; Reduction, Cumulative fecundity and spawning ; Reduction, Plasma vitellogenin concentrations ; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development ; Decrease, Population trajectory ; Antagonism, Estrogen receptor

Decreased, Sodium conductance 1 ; Reduced, swimming speed ; Reduced, feeding 1 ; Increased, predation ; Reduced, survival ; Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel

Interaction (VSGCs) ; chloride-permeable ion channels ; voltage-gated calcium channels ; ligand-gated chloride channels ; Seizures ; Death ; Loss of consciousness ; Signaling disruption ; Convolutions ; Tremors ; Paralysis ; Neuronal membrane potential disruption ; Disruption of homeostasis of neuronal networks ; Movement Impariment ; Behavioral Changes ; Population reduction

Decrease, Population trajectory ; Increase, Reactive oxygen species production ; Peptide Oxidation ; Decrease, Ovulation ; Decrease, Fertility ; Increase, DNA damage ; Increase, Excessive reactive oxygen species generation ; Increase, Apoptosis ; Decrease, Oogenesis ; Increase, Follicular atresia ; Decrease, Fecundity

Decrease, Mitochondrial ATP production ; Increase, Reactive oxygen species production ; Decrease, Ovulation ; Decrease, Fertility ; Decrease, Oogenesis ; Increase, Lipid peroxidation ; Increase, Uncoupling of oxidative phosphorylation ; Decrease, Fecundity

Inhibition, PTGS-1 (Prostaglandin-endoperoxide synthase 1) ; Activation, PTGS-1 (Prostaglandin-endoperoxide synthase 1) ; Activation, PTGS-2 (Prostaglandin-endoperoxide synthase 2) ; Inhibition, PTGS-2 (Prostaglandin-endoperoxide synthase 2) ; Increase, bicarbonate ; Increase, mucous ; Increase, mucosal blood flow ; Increase, platelet aggregation ; Increase, angiogenesis ; Decrease, leukocyte adherence ; Increase, leukocyte adherence ; Activate, leukocyte ; Activate, mucosal defense ; Increase, surfactant ; Decrease, surfactant ; Activate, phospholipase ; Increase, ammonium (NH4+) ; Inhibit, gastric ulcer formation ; Activated, gastric ulcer formation

impaired, Fertility ; Reduction, Testosterone synthesis in Leydig cells ; Reduction, testosterone level ; Glucocorticoid Receptor Agonist, Activation ; Repressed expression of steroidogenic enzymes ; Increased apoptosis, decreased number of adult Leydig Cells ; Decreased Sperm Number, Reduced Fertility ; Accelerated Epididymal Sperm Transit, Reduced Fertility ; Abnormal Sperm Maturation, Reduced Fertility ; Decreased sperm quantity or quality in the adult, Decreased fertility

Activation, Glucocorticoid Receptor ; Inhibition, Nuclear factor kappa B (NF-kB) ; Suppression, Inflammatory cytokines ; Decreased, Lymphocytes ; Induction, IKB inhibitory protein ; Suppression, Immune system ; Increased, Disease susceptibility

Increased, Mortality ; Activation, Glutamate-gated chloride channel ; Increased, Chloride conductance ; hyperpolarisation, neuron ; N/A, Ataxia, paralysis, or hyperactivity ; Decreased, population 1

Increased, Mortality ; Increased, Chloride conductance ; Increased, Inhibitory postsynaptic potential ; Increased, Neuronal synaptic inhibition ; Inhibition, Feeding ; Activation, Glutamate-gated chloride channels ; Induction, pharyngeal muscle paralysis

Decreased, GnRH pulsatility/release in hypothalamus ; Decreased, LH Surge from anterior pituitary ; interruption, Ovulation ; prolonged, estrus ; Increased, circulating estrogen levels ; Increased, prolactin exposure ; Hyperplasia, Mammary gland ; Increased, latency period ; Increased, Adenomas/carcinomas (mammary)

Decreased, GnRH pulsatility/release in hypothalamus ; Decreased, LH Surge from anterior pituitary ; interruption, Ovulation ; prolonged, estrus ; Increased, circulating estrogen levels ; Increased, lactotroph hyperplasia and hypertrophy ; Increased, adenomas (pituitary)

Decrease, surfactant ; Activate, phospholipase ; Increase, ammonium (NH4+) ; Activated, gastric ulcer formation ; Reduced, mucosal defense ; Helicobacter pylori infection

Thyroxine (T4) in serum, Decreased ; Induction, Upregulation of glucuronyltransferase activity ; Increase, Biliary excretion TH glucuronide ; Decreased, Thyroxine (T4) in tissues ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis ; Activation, Hepatic nuclear receptor(s) ; Increased, Hepatic thyroid hormone uptake/transport

Impairment, Learning and memory ; Increased, predation ; Antagonism, Histamine Receptor (H2) ; Decrease, histaminergic neuron excitation ; N/A, sedation ; Decreased, locomotion ; impaired, Learning and memory ; Decreased, survival

Apoptosis ; Histone deacetylase inhibition ; Histone acetylation, increase ; p21 (CDKN1A) expression, increase ; cell cycle, disrupted ; testicular toxicity ; spermatocyte depletion

Inhibition, HMG-CoA reductase ; Decreased, mevalonate ; Decreased, cholesterol ; Decreased, Testosterone ; malformed, Male reproductive tract ; Decrease, Fertility

Suppression, HNF4alpha

Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme ; Increased, Plasma tyrosine ; Increase, Cytotoxicity (corneal cells) ; Increase, Inflammation (corneal cells) ; Increase, Regenerative cell proliferation (corneal cells) ; Increase, Papillomas/carcinomas (squamous cells)

Increase, Dopaminergic activity ; Decreased, Prolactin ; Increased, Estrogen receptor (ER) activity ; Decreased, Progesterone from corpus luteum ; Increase, Hyperplasia (glandular epithelial cells of endometrium) ; Increase, Endometrial adenocarcinomas

Abnormal, Foraging activity and behavior ; Death/Failure, Colony ; Decrease, Number of worker bees ; Increase, Energetic demands and therefore metabolic stress ; Increased, Appetite and hunger

Pulmonary fibrosis ; Increased, interaction with the resident cell membrane components ; Increased, secretion of proinflammatory and profibrotic mediators ; Increased, recruitment of inflammatory cells ; Increased, loss of alveolar capillary membrane integrity ; Increased, activation of T (T) helper (h) type 2 cells ; Increased, fibroblast proliferation and myofibroblast differentiation ; Increased, extracellular matrix deposition

Increase, Hyperplasia (Leydig cells) ; Increase, Leydig cell tumors ; Inhibition, 5α-reductase activity ; Increased, Leutinizing hormone (LH) ; Decrease, Bioactivation of testosterone

Inhibition of ATP synthase ; Death ; Reduced ATP formation ; Inhibition of ATP-dependent cellular functions ; Reduced ATP-depndent functions ; Heart Failure ; Respiratory Failure ; Increased metabolism ; Reduced mitochondrial oxygen consumption ; Increased mitochondrial reactive oxygen species formation ; Necrosis ; Apoptosis ; Hyperpolarized mitochondrial membrane potential ; Population reduction

Binding, Immunophilins ; Inhibition, Calcineurin Activity ; Interference, nuclear localization of NFAT ; Reduction, NFAT/AP-1 complex formation ; Suppression, IL-2 and IL-4 production ; Suppression, Suppression of production of cytotoxic T-cells ; Suppression, Suppression of T-cell dependent antibody production ; Impairment, T-cell dependent antibody response ; Relief, Relief of atopic dermatitis ; Increase, Increased susceptibility to infection

Inhibition of complex I ; Inhibition of complex II ; Inhibition of complex III ; Inhibition of complex IV ; Death ; Reduced ATP formation ; Inhibition of ATP-dependent cellular functions ; Reduced ATP-depndent functions ; Heart Failure ; Respiratory Failure ; Increased metabolism ; Inhibition of the electron transport chain ; Reduced mitochondrial oxygen consumption ; Reduced mitochondrial membrane potential ; Increased mitochondrial reactive oxygen species formation ; Necrosis ; Apoptosis ; Population reduction

Decreased, Population trajectory ; Decreased, Reproductive Success ; CYP7B activity, inhibition ; 7α-hydroxypregnenolone synthesis in the brain, decreased ; Dopamine release in the brain, decreased ; Locomotor activity, decreased

Decreased, Population trajectory ; Decreased, Reproductive Success ; CYP7B activity, inhibition ; 7α-hydroxypregnenolone synthesis in the brain, decreased ; Dopamine release in the brain, decreased ; Sexual behavior, decreased

Activation, PPARα ; Activation, LXR ; peroxisome proliferator activated receptor promoter demethylation ; Activation, FAS ; Activation, SCD-1 ; Inhibition, Mitochondrial fatty acid beta-oxidation ; Inhibition, PPAR alpha ; Increased, Liver Steatosis ; Activation, NRF2 ; Activation, SHP ; Increased, Reactive oxygen species ; Increase, insulin ; Activation, insulin receptor ; Activation, mTORC2 ; Activation, AKT ; Activation, mTORC1 ; Activation, SREBP-1 ; Activation, L-FABP ; Increase, cytosolic fatty acid ; Increased, lipogenesis ; Activation, FXR ; Activation, HSD17B4 ; Inhibition, LXR ; Inhibition, LRH-1 ; Activation, aPKC ; Activation, PI3K ; Inhibition, Steatosis ; Induction, fatty acid beta-oxidation ; Decrease, cytosolic fatty acid ; Activation, LRH-1 ; Inhibition, Fatty Acid Beta Oxidation ; N/A, Steatohepatisis ; Increased, Oncotic Necrosis

Inhibition of histone deacetylases (HDACs) class I ; De-repression of the Wnt/beta-catenin signalling pathway ; Accumulation of beta-catenin ; Activation of Wnt target genes ; Valproic acid exposure developmental outcome

Production, Critical Metabolites (CGA 330050 and CGA 265307) ; Induction, Liver “Dysfunctional” Changes by CGA 330050 ; Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307 ; Induction, Sustained Hepatotoxicity ; Induction, Sustained Cell Proliferation ; Formation, Liver tumor

Decreased, Uptake of inorganic iodide ; Increase, Hypertrophy and proliferation (follicular cell) ; Increase, Hyperplasia (follicular cells) ; Increase, Thyroid-stimulating hormone (TSH) ; Decrease, Serum thyroid hormone (T4/T3) ; Increase, Adenomas/carcinomas (follicular cell)

Decreased, survival ; Reduced, Swimming performance ; Thiol group of chemicals interact with sulfuhydryl groups of proteins to form thiol adducts ; Inhibition of lysyl oxidase ; Reduction of collagen crosslinking ; Weak collagen matrix ; Notochord distortion or malformations ; Growth, reduction

Increase, Cytotoxicity (renal tubular cell) ; Occurrence, Kidney toxicity ; Inhibition of mitochondrial DNA polymerase gamma (Pol gamma) ; Depletion, mtDNA ; Dysfunction, Mitochondria

Thyroxine (T4) in neuronal tissue, Decreased ; Thyroxine (T4) in serum, Decreased ; Reduced levels of BDNF ; Impairment, Learning and memory ; Decrease of synaptogenesis ; Decrease of neuronal network function ; Thyroid hormone synthesis, Decreased ; Inhibition, Na+/I- symporter (NIS) ; Decrease of Thyroidal iodide ; Decrease of GABAergic interneurons

Peptide Oxidation ; Increase, Adenomas/carcinomas (hepatocellular) ; Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme ; Increase, Cytotoxicity ; Increased, Induction of pyruvate dehydrogenase (PDH) ; Increase, Oxidative metabolism

Inhibition of the enzyme 5-alpha reductase type 2 ; Decrease in dihydrotestosterone conversion from testosterone ; Decrease in transcription of androgen-dependent genes ; Alteration of proliferation and differentiation of several androgen dependent tissues ; Developmental toxicity by inhibition of the 5-alpha reductase enzyme

Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) ; Inhibition, NADH-ubiquinone oxidoreductase (complex I) ; N/A, Mitochondrial dysfunction 1 ; impaired, Proteostasis ; N/A, Neuroinflammation ; Degeneration of dopaminergic neurons of the nigrostriatal pathway ; Parkinsonian motor deficits

Thyroperoxidase, Inhibition ; Increase, Hypertrophy and proliferation (follicular cell) ; Increase, Hyperplasia (follicular cells) ; Increase, Thyroid-stimulating hormone (TSH) ; Decrease, Serum thyroid hormone (T4/T3) ; Increase, Adenomas/carcinomas (follicular cell) ; Decrease, Incorporation of active iodide into iodotyrosines

Reduction, Plasma 17beta-estradiol concentrations ; Reduction, Cumulative fecundity and spawning ; Reduction, Plasma vitellogenin concentrations ; Thyroperoxidase, Inhibition ; Thyroid hormone synthesis, Decreased

Thyroxine (T4) in neuronal tissue, Decreased ; Thyroxine (T4) in serum, Decreased ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered ; Hippocampal gene expression, Altered ; Thyroperoxidase, Inhibition ; Thyroid hormone synthesis, Decreased ; Cognitive Function, Decreased

Thyroxine (T4) in neuronal tissue, Decreased ; Thyroxine (T4) in serum, Decreased ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered ; Hippocampal gene expression, Altered ; Cognitive Function, Decreased ; Binding, Transthyretin in serum ; Displacement, Serum thyroxine (T4) from transthyretin ; Increased, Free serum thyroxine (T4) ; Increased, Uptake of thyroxine into tissue ; Increased, Clearance of thyroxine from tissues

Increase, Cytotoxicity ; Decrease, Intracellular pH ; Increase, Tissue Degeneration, Necrosis & Atrophy ; Increase, Cell Proliferation ; Increase, Respiratory or Squamous Metaplasia ; Increase, Mutations in Critical Genes ; Increase, Site of Contact Nasal Tumors

Thyroid hormone synthesis, Decreased ; Decrease of Thyroidal iodide ; Decreased, Thyroxine (T4) in serum ; Decreased, Thyroxine (T4) in tissues ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis ; Inhibition, Iodotyrosine deiodinase (IYD)

Increased, Mortality ; Increased, Chloride conductance ; Activation, ionotropic GABA Receptor chloride channel ; Increased, Inhibitory postsynaptic potential ; Induction, Somatic muscle paralysis ; Increased, Neuronal synaptic inhibition ; Inhibition, Feeding

Reproductive failure ; Activation, JAK/STAT pathway ; Activation, TGF-beta pathway

Decline, Population ; Activation, Juvenile hormone receptor ; Induction, Doublesex1 gene ; Induction, Male reproductive tract ; Increased, Male offspring ; Alteration, Food-web structures

Thyroid hormone synthesis, Decreased ; Decreased, Thyroxine (T4) in serum ; Decreased, Glomerular filtration ; Decreased, Renal plasma flow ; Decreased, Sodium reabsorption ; Increased, Serum creatinine ; Occurrence, Cystic dilatation (renal tubule) ; Occurrence, Cytoplasmic vacuolization (podocyte) ; Occurrence, Cytoplasmic vacuolization (Renal tubule) ; Decreased, Renal ability to dilute urine ; Occurrence, Kidney toxicity

Activation, 5HT2c ; N/A, Unknown ; Increased, Kidney Failure

Increase, Reactive oxygen species production ; Accumulation, Collagen ; Increased, secretion of local growth factors ; Expression of Collagen ; Collagen Deposition ; Induction, Cell damage sensing ; Incudtion, Sustained inflammatory cytokine release ; Increase, Differentiation of fibroblasts ; Induction, Epithelial Mesenchymal Transition ; Pulmonary fibrosis ; Activation, Latent Transforming Growth Factor Beta 1 ; Activation, Transforming Growth Factor beta pathway

Blockade, L-Type Calcium Channels ; Decrease, Calcium currents ; Decrease, Calcium binding to Troponin C ; Decrease, Cardiac contractility ; Decrease, Cardiac ejection fraction ; Decrease, Blood pressure ; Heart failure ; Disruption, Intracellular calcium mobilization ; Disruption, Sarcomere assembly

Activation, LXR ; peroxisome proliferator activated receptor promoter demethylation ; Up Regulation, CD36 ; Increase, FA Influx ; Activation, ChREBP ; Activation, SREBP-1c ; Activation, FAS ; Activation, SCD-1 ; Synthesis, De Novo FA ; Accumulation, Triglyceride ; Damaging, Mitochondria ; N/A, Liver Steatosis

N/A, Mitochondrial dysfunction 1 ; N/A, Cell injury/death ; Release, Cytokine ; Peptide Oxidation ; Disruption, Lysosome ; Infiltration, Inflammatory cells ; Inflammation, Liver

Activation, Glucocorticoid Receptor ; Decreased, serotonin transporter activity ; Increased, extracellular serotonin ; Decreased, intracellular serotonin ; Decreased, packaged serotonin ; Decreased, synaptic release ; Inactivated, 5-HTR (serotonin receptors) ; Reduce expression, BDNF (Brain-derived neurotrophic factor) ; Decreased, neuroplasticity ; Increase, cortisone ; Reduced, BDNF (Brain-derived neurotrophic factor) ; Increased, agitation ; Decreased, extracellular serotonin ; Increased, glucocorticoid receptor activity

Decreased testosterone by the fetal Leydig cells, Increased corticosterone ; Decreased testosterone by the fetal Leydig cells, Activation by other glucocorticoid receptor agonists ; Decreased testosterone by the fetal Leydig cells, Increased COUP-TFII in fetal Leydig cells ; Decreased number and function of adult Leydig cells, Decreased COUP-TFII stem Leydig cells ; Decreased testosterone by the fetal Leydig cells, Dysgenesis of fetal Leydig cells ; Decreased sperm quantity / quality in the adult, Decreased fertility

Decreased testosterone by the fetal Leydig cells, Increased COUP-TFII in fetal Leydig cells ; Decreased number and function of adult Leydig cells, Decreased COUP-TFII stem Leydig cells ; Decreased testosterone by the fetal Leydig cells, Dysgenesis of fetal Leydig cells ; Decreased sperm quantity / quality in the adult, Decreased fertility ; Decreased testosterone by the fetal Leydig cells, Alterations in the fetal testis proteome

Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol ; Decreased Cholesterol, Decreased Uptake of Lipoproteins ; Decreased Cholesterol, Decreased Transport of Cholesterol to the Inner Mitochondrial Membrane ; Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells ; Decreased Cholesterol, Decreased sperm quantity and/or quality in the adult testis

Decreased testosterone by the fetal Leydig cells, Increased COUP-TFII in fetal Leydig cells ; Decreased number and function of adult Leydig cells, Decreased COUP-TFII stem Leydig cells ; Decreased sperm quantity / quality in the adult, Decreased fertility ; Decreased testosterone by the fetal Leydig cells, Increased estradiol ; Decreased testosterone by the fetal Leydig cells, Activation by other estradiol agonists ; decreased testosterone by fetal Leydig cells, Dysgenesis of fetal Leydig cells

Decreased sperm quantity or quality in the adult, Decreased fertility ; Stimulation of adult Leydig cells via the Adrenal Corticosterone, Increased Glucocorticoid ; Apoptosis of adult Leydig cells, Decreased testosterone by adult Leydig cells ; Glucocorticoid Receptor mediated alterations in steriodogenic enzymes, Decreased testosterone by adult Leydig cells ; Direct effects of Corticosterone on steroidogenesis, Decreased testosterone by adult Leydig cells

Decreased testosterone by the fetal Leydig cells, Increased COUP-TFII in fetal Leydig cells ; Decreased testosterone by the fetal Leydig cells, Hypermethylation in the fetal testis ; Decreased testosterone by the fetal Leydig cells, Dysgensis of fetal Leydig cells ; Decreased testosterone by the fetal Leydig cells, Decreased COUP-TFII stem Leydig cells ; Decreased fertility in the adult, Decreased sperm quantity and/or quality in the adult testis

Decreased steroidogenesis, Proteomic alterations in the adult Leydig cell ; Decreased steroidogenesis, Decreased Activity of Steroidogenic Enzymes in Adult Leydig cells ; Decreased steroidogenesis, Increased Apoptosis of Adult Leydig Cells ; Decreased steroidogenesis, Alterations in the Leydig Cell Cytoskeleton ; Decreased sperm quantity or quality in the adult, Decreased fertility

Increased, intracellular sodium (Na+) ; Increased, intracellular chloride (Cl-) ; Activated, presynaptic neuron 1 ; Increased, glutamate ; Activated, NMDA receptor ; Activated, voltage-gated sodium channel ; Inhibit, voltage-gated sodium channel ; Treat, carbamazepine ; Activated, membrane depolarization ; Inactive, membrane depolarization ; Increased, RDX dose ; Repress, GABA-A receptor ; Activate, GABA-A receptor ; Activate, presynaptic neuron 2 ; Increase, GABA ; Increase, seizure ; Increased, hippocampal hyperdepolarization ; Increased, epilepsy

Mu Opioid Receptor Agonism ; Release of G Proteins ; Analgesia ; Inhibition of N-type Ca ion channels ; Inhibition of neurotransmitter vesicle release

hyperpolarisation, neuron ; Mu Opioid Receptor Agonism ; Release of G Proteins ; Opening of G protein gated inward rectifying K channels ; Analgesia

Damaging, Mitochondria ; Apoptosis ; Activation, NADPH Oxidase ; ROS formation ; Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK ; Activation, HIF-1 ; Increased, DNA Damage-Repair ; Reproductive failure

Accumulation, Biological membranes ; Disruption, Membrane integrity

Activation, Glucocorticoid Receptor ; Inhibit, serotonin transporter activity ; Decreased, serotonin transporter activity ; Decreased, extracellular sodium (Na+) ; Decreased, extracellular chloride (Cl-) ; Increased, extracellular serotonin ; Increased, intracellular sodium (Na+) ; Increased, intracellular chloride (Cl-) ; Decreased, intracellular serotonin ; Decreased, packaged serotonin ; Decreased, synaptic release ; Increased, 5-HT3 (5-hydroxytryptamine) ; Inactivated, 5-HTR (serotonin receptors) ; Reduce expression, BDNF (Brain-derived neurotrophic factor) ; Decreased, neuroplasticity ; Increase, cortisone ; Reduced, BDNF (Brain-derived neurotrophic factor) ; Activation, 5-HT2A (Serotonin 2A) ; Activate, PLC (Phospholipase C) ; Increase, inositol triphosphate ; Increase, intracellular calcium ; Activate, calmodulin ; Increase, myosin light chain phosphorylation ; Increase, vascular smooth muscle contraction ; Increased, seizure ; Increased, agitation ; Increased, depression ; Increase, hypertension ; Decreased, extracellular serotonin

NFE2/Nrf2 repression ; Reduced, FXR activity ; Reduced, SHP activity ; Activated, LXR ; Reduced, PPARalpha ; Reduced, HSD17B4 activity ; Reduced, fatty acid beta oxidation ; Increased, steatosis

Activation, PPARα ; Inhibition, Mitochondrial fatty acid beta-oxidation ; Increased, De Novo FA synthesis ; Increased, Liver Steatosis ; Activation, NRF2 ; Activation, NR1H4 ; Activation, SHP ; Decreased, DHB4/HSD17B4 ; Activation, LXR alpha ; Inhibition, SREBP1c ; Activation, MTTP ; Increased, ApoB100 ; Increased, Triglyceride ; FA synthesis

N/A, Mitochondrial dysfunction 1 ; Impairment, Learning and memory ; Activation, Nicotinic acetylcholine receptor ; Abnormal, Foraging activity and behavior ; Weakened, Colony ; Altered, Ca2+-calmodulin activated signal transduction ; Death/Failure, Colony

N/A, Mitochondrial dysfunction 1 ; Impairment, Learning and memory ; Activation, Nicotinic acetylcholine receptor ; Abnormal, Foraging activity and behavior ; Weakened, Colony ; Altered, Ca2+-calmodulin activated signal transduction ; Death/Failure, Colony ; Abnormal, Role change within caste

Impairment, Learning and memory ; Activation, Nicotinic acetylcholine receptor ; Abnormal, Foraging activity and behavior ; Weakened, Colony ; Altered, Ca2+-calmodulin activated signal transduction ; Death/Failure, Colony ; Desensitization, Nicotinic acetylcholine receptor

N/A, Mitochondrial dysfunction 1 ; Impairment, Learning and memory ; Decrease of neuronal network function ; Activation, Nicotinic acetylcholine receptor ; Death/Failure, Colony ; Abnormal, Roll change within caste ; Reduced, Brood care ; impaired, Larval development

Impairment, Learning and memory ; Decrease of neuronal network function ; Activation, Nicotinic acetylcholine receptor ; Death/Failure, Colony ; Abnormal, Roll change within caste ; Reduced, Brood care ; impaired, Larval development ; Desensitization, Nicotinic acetylcholine receptor

N/A, Mitochondrial dysfunction 1 ; Activation, Nicotinic acetylcholine receptor ; Death/Failure, Colony ; impaired, Hive thermoregulation ; Accumulation, Damaged mitochondrial DNA ; Accelerated, Aging ; Overwhelmed, Mitochondrial DNA repair mechanisms ; Decrease, Number of worker bees

N/A, Mitochondrial dysfunction 1 ; Activation, Nicotinic acetylcholine receptor ; Weakened, Colony ; Death/Failure, Colony ; impaired, Hive thermoregulation

N/A, Mitochondrial dysfunction 1 ; Activation, Nicotinic acetylcholine receptor ; Weakened, Colony ; Death/Failure, Colony

Impairment, Learning and memory ; Activation, Nicotinic acetylcholine receptor ; Abnormal, Foraging activity and behavior ; Weakened, Colony ; Altered, Ca2+-calmodulin activated signal transduction ; Death/Failure, Colony ; Abnormal, Role change within caste ; Desensitization, Nicotinic acetylcholine receptor

Weakened, Colony ; Death/Failure, Colony ; Abnormal, Role change within caste

Abnormal, Foraging activity and behavior ; Weakened, Colony ; Death/Failure, Colony ; Increased, Energetic demands and therefore metabolic stress

Activation, PXR/SXR ; Up Regulation, CD36 ; Accumulation, Fatty acid ; Decreased, Mitochondrial fatty acid beta-oxidation ; Increased, FA Influx ; Increased, Triglyceride formation ; Up Regulation, SCD-1 ; Increased, Liver Steatosis ; Inhibition, FoxA2 ; Down Regulation, CPT1A ; Down Regulation, HMGCS2 ; Increased, Hepatic Triglycerides ; Accumulation, Hepatic FA ; Decreased, Ketogenesis

Activation, LXR ; peroxisome proliferator activated receptor promoter demethylation ; Up Regulation, CD36 ; Activation, ChREBP ; Accumulation, Fatty acid ; Inhibition, Mitochondrial fatty acid beta-oxidation ; Increased, FA Influx ; Suppression, Constitutive androstane receptor, NR1l3 ; Inhibition, PPAR alpha ; Activation, SREBF1 ; Increased, De Novo FA synthesis ; Increased, Fatty acid uptake ; Increased, Triglyceride formation ; Up Regulation, SCD-1 ; Up Regulation, FAS ; Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) ; Increased, Liver Steatosis

Activated, gastric ulcer formation ; Reduced, PTGS1 function ; Reduced, platelet aggregation ; Decreased, mucosal blood flow ; Reduced, mucosal defense ; Decreased, mucous ; Decreased, bicarbonate

Activated, gastric ulcer formation ; Reduced, PTGS2 function ; Decreased, angiogenesis ; Increased, leukocyte adherence ; Increased, leukocyte activation

Increased, Mortality ; Decline, Population ; Inhibition, organic anion transporter 1 (OAT1) ; Increased, blood uric acid concentration ; Occurrence, renal proximal tubular necrosis ; Increased, blood potassium concentration ; Occurrence, tophi (urate) deposition ; Occurrence, cardiac arrhythmia ; Increased, Oxidative Stress

Oxidation of hemoglobin (methemoglobin) ; Oxidative stress in red blood cells ; Reduced oxygen supply and hypoxia ; Respiration changes ; Headache and fatigue ; Seizures ; Death ; Population reduction

N/A, Parent compound is converted to the reactive metabolite and forms free radicals leading to oxidation of heme iron(II) in hemoglobin to iron(III) ; Altered regulation, Alpha hemoglobin ; Propagation, Oxidative stress ; Damaging, Red blood cells; hemolysis ; Formation, Formation of hemoglobin adducts ; Down Regulation, Gulcose-6-phosphate dehydrogenase ; Increase, RBC congestion in liver ; Increase, Liver and splenic hemosiderosis ; N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number ; N/A, Cyanosis occurs

Binding to the NMDA receptor ; Binding to the nACh receptor ; Binding to the GABA A receptor ; Hydrophobic binding to proteins and membranes ; Death ; Reduced membrane current ; Decreased channel open time ; Increased channel open time ; Reduction of all cell functions ; Reduced Excitatory Transmition ; Reduced Excitatory of the Hippocampus ; Facilitated Inhibitory Transmission Cortex-Thalamus ; Reversible decrease of organ functions ; Sedation ; Excitability ; Population reduction

Thyroid hormone synthesis, Decreased ; Decreased, Thyroxine (T4) in serum ; Decreased, Thyroxine (T4) in tissues ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis ; Inhibition, Pendrin

Peptide Oxidation ; Oxidation, Glutathione (To be considered with MIE) ; KE1 : S-Glutathionylation, eNOS ; KE2 : Decrease, GTPCH-1 ; KE3 : Decrease, Tetrahydrobiopterin ; KE4 : Uncoupling, eNOS ; KE6 : Depletion, Nitric Oxide ; KE7 : Impaired, Vasodilation ; KE8 : Increase, Vascular Resistance ; KE5 : Decrease, AKT/eNOS activity ; Hypertension

Activation, PXR/SXR

Decreased, PPAR-alpha activation ; Decreased, PPAR-beta activation ; Decreased, PPAR-gamma activation ; Accumulation, Fatty acid ; Decreased, HSD17B10 expression ; Decreased, Mitochondrial fatty acid beta-oxidation ; Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity ; Undefined, Liver Steatosis ; Increased, Liver Steatosis

Increase, Inflammation ; Inactivation of PPARγ ; Activation of TGF-β signaling ; Differentiation of Myofibroblast ; Production of α-smooth muscle actin ; Expression of Collagen ; Collagen Deposition ; Lung fibrosis ; Induction, Epithelial Mesenchymal Transition ; Activation of PPARγ

Up Regulation, SREBF2 ; Up Regulation, Unsaturated fatty acid ; Down Regulation, GSS and GSTs gene ; Glutathione synthesis ; Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene ; Perturbation of cholesterol ; Glutathione homeostasis ; Hepatotoxicity

Inhibition, Phospholipase A ; Damage, Lipid bilayer ; Disturbance, Lysosomal function ; Injury, Mitochondria ; Occurrence, Cytoplasmic vacuolization (hepatocyte) ; Occurrence, Ballooning degeneration (hepatocyte) ; Occurrence, Cytoplasmic vacuolization (kupffer cell) ; Induction, Microvesicular fat ; Formation, Mallory body ; Occurrence, Cytoplasmic vacuolization (Bile duct cell) ; Formation, Liver fibrosis

Increased, PPAR-alpha activation ; Decreased, bile flow ; Increased, cholestasis ; Alteration, lipid metabolism ; prolonged, elevation of serun CCK ; Increased, Cellular proliferation / hyperplasia of acinar cells ; Increased, Pancreatic acinar tumors

Activation, PPARα ; modulation, Genes/proteins that regulate hepatocyte fate ; Increase, Mitogenic cell proliferation (hepatocytes) ; Increase, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci ; Increase, Adenomas/carcinomas (hepatocellular)

Activation of specific nuclear receptors, PPAR-gamma activation ; Increased, adipogenesis ; Increased, secretion of local growth factors ; Increased, proliferation of mesenchymal cells ; Increased, IGF-1 (mouse) ; Increased, Firbrosarcoma ; Increased, liposarcoma ; Increased, hemagiosarcoma

impaired, Fertility ; Activation, PPARα ; Decrease, Steroidogenic acute regulatory protein (STAR) ; Reduction, Cholesterol transport in mitochondria ; Reduction, Testosterone synthesis in Leydig cells ; Reduction, testosterone level ; Decrease, Translocator protein (TSPO) ; Malformation, Male reproductive tract

impaired, Fertility ; Activation, PPARα ; Reduction, Cholesterol transport in mitochondria ; Reduction, Testosterone synthesis in Leydig cells ; Reduction, testosterone level ; Increase, Luteinizing hormone (LH) ; Hyperplasia, Leydig cell ; Increase proliferation, Leydig cell

Increased, intracellular sodium (Na+) ; Increased, seizure ; Activated, presynaptic neuron 1 ; Increased, glutamate ; Activated, NMDA receptor ; Activated, voltage-gated sodium channel ; Inhibit, voltage-gated sodium channel ; Treat, carbamazepine ; Activated, membrane depolarization ; Increased, hippocampal hyperdepolarization ; Increased, epilepsy

Increased, seizure ; Activated, membrane depolarization ; Increased, RDX dose ; Increased, hippocampal hyperdepolarization ; Increased, epilepsy ; Reduced, presynaptic neuron 2 activity ; Decreased, GABA ; Reduced, GABA-A receptor activation ; Decreased, intracellular chloride

Reduction, Plasma 17beta-estradiol concentrations ; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells ; Reduction, Vitellogenin synthesis in liver ; Reduction, Cumulative fecundity and spawning ; Reduction, Plasma vitellogenin concentrations ; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development ; Decrease, Population trajectory ; Inhibition, Prolyl hydroxylases ; Increased, HIF-1 heterodimer ; Decreased, Aromatase (Cyp19a1) mRNA

N/A, Cell injury/death ; Alkylation, Protein ; Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) ; Up Regulation, TGFbeta1 expression ; Activation, Stellate cells ; Accumulation, Collagen ; N/A, Liver fibrosis ; Tissue resident cell activation ; Increased Pro-inflammatory mediators

Weakened, Colony ; Death/Failure, Colony

Increase, Cytotoxicity (renal tubular cell) ; Occurrence, Kidney toxicity ; Disturbance, Lysosomal function ; Disruption, Lysosome ; Binding of substrate, endocytic receptor

Decrease, Mitochondrial ATP production ; Alkylation, Protein ; Increase, Cytotoxicity (renal tubular cell) ; Occurrence, Kidney toxicity ; Dysfunction, Mitochondria

Binding to the retinoic acid receptor (agonism) ; Transcription of retinoic acid regulated genes ; Repression of the Wnt signalling pathway ; Developmental toxicity of retinoic acid

Sensing of the stressor by pulmonary cells ; Increased production of pulmonary, pro-inflammatory cytokines ; Increased production of pulmonary SAA ; Formation of HDL-SAA ; Increased systemic total cholesterol pool ; Foam cell formation ; Plaque progression in arteries

N/A, Covalent binding to protein, possibly lysine residue ; Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways ; Increase, Allergic Respiratory Hypersensitivity Response ; Activation, Dendritic Cells ; Activation/Proliferation, T-cells

Release of G Proteins ; Inhibition of N-type Ca ion channels ; Inhibition of neurotransmitter vesicle release ; Serotonin 1A Receptor Agonism ; Anti-depressant Activity

hyperpolarisation, neuron ; Release of G Proteins ; Opening of G protein gated inward rectifying K channels ; Serotonin 1A Receptor Agonism ; Anti-depressant Activity

Decreased, serotonin transporter activity ; Increased, extracellular serotonin ; Decreased, intracellular serotonin ; Decreased, packaged serotonin ; Decreased, synaptic release ; Inactivated, 5-HTR (serotonin receptors) ; Reduce expression, BDNF (Brain-derived neurotrophic factor) ; Decreased, neuroplasticity ; Increased, agitation ; Decreased, extracellular serotonin ; Increased, serotonin transporter activity ; Increased, intracellular serotonin ; Increased, packaged serotonin ; Increased, synaptic release

Inhibit, serotonin transporter activity ; Decreased, serotonin transporter activity ; Increased, extracellular serotonin ; Decreased, intracellular serotonin ; Decreased, packaged serotonin ; Decreased, synaptic release ; Inactivated, 5-HTR (serotonin receptors) ; Reduce expression, BDNF (Brain-derived neurotrophic factor) ; Decreased, neuroplasticity ; Reduced, BDNF (Brain-derived neurotrophic factor) ; Increased, depression ; Decreased, extracellular serotonin ; Increased, serotonin transporter activity ; Increased, intracellular serotonin ; Increased, packaged serotonin ; Increased, synaptic release

Decreased, serotonin transporter activity ; Increased, extracellular serotonin ; Decreased, intracellular serotonin ; Decreased, packaged serotonin ; Decreased, synaptic release ; Increased, 5-HT3 (5-hydroxytryptamine) ; Increased, seizure ; Decreased, extracellular serotonin ; Increased, serotonin transporter activity ; Increased, intracellular serotonin ; Increased, packaged serotonin ; Increased, synaptic release ; Decreased, 5-HT3

Inhibition, sodium channel ; Decreased, sodium conductance 2 ; Decreased, GABA release

Increased, Atrioventricular block and bradycardia ; Increased, Respiratory distress/arrest ; Inhibition, sodium channel ; Decreased, Sodium conductance 1 ; N/A, hypoxia ; Increased, amputations

Inhibition, sodium channel ; Decreased, Sodium conductance 1 ; Reduced, swimming speed ; Increased, predation

Inhibition, sodium channel ; Decreased, Sodium conductance 1 ; Reduced, swimming speed ; Reduced, feeding 1 ; Increased, predation ; Reduced, survival

Thyroxine (T4) in neuronal tissue, Decreased ; Thyroxine (T4) in serum, Decreased ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered ; Hippocampal gene expression, Altered ; Thyroid hormone synthesis, Decreased ; Cognitive Function, Decreased ; Inhibition, Na+/I- symporter (NIS) ; Decrease of Thyroidal iodide ; Decreased, Thyroxine (T4) in serum

Thyroxine (T4) in serum, Decreased ; Thyroid hormone synthesis, Decreased ; Inhibition, Na+/I- symporter (NIS) ; Decrease of Thyroidal iodide ; Decreased, Thyroxine (T4) in tissues ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis

Decreased, serotonin transporter activity ; Increased, extracellular serotonin ; Decreased, intracellular serotonin ; Decreased, packaged serotonin ; Decreased, synaptic release ; Activation, 5-HT2A (Serotonin 2A) ; Activate, PLC (Phospholipase C) ; Increase, inositol triphosphate ; Increase, intracellular calcium ; Activate, calmodulin ; Increase, myosin light chain phosphorylation ; Increase, vascular smooth muscle contraction ; Increase, hypertension ; Decreased, extracellular serotonin

Increase, Mortality ; Decrease, Cuticular chitin synthesis ; Increase, Premature molting ; Increase, Sulfonylurea receptor binding ; Increase, Opening of voltage-dependent calcium channel ; Increase, Cell membrane depolarization

Suppression, Immune system ; Abnormal, Foraging activity and behavior ; Death/Failure, Colony ; Decrease, Number of worker bees ; Increased, Viral susceptibility

Suppression, Immune system ; Death/Failure, Colony ; impaired, Hive thermoregulation ; Decrease, Number of worker bees ; Increased, Viral susceptibility ; impaired, Development

Activation, Long term AHR receptor driven direct and indirect gene expression changes ; N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects ; Changes/Inhibition, Cellular Homeostasis and Apoptosis ; Alterations, Cellular proliferation / hyperplasia ; Formation, Hepatocellular and Bile duct tumors

Thyroxine (T4) in serum, Decreased ; Thyroperoxidase, Inhibition ; Thyroid hormone synthesis, Decreased ; Decreased, Thyroxine (T4) in tissues ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis

Thyroxine (T4) in serum, Decreased ; Decrease, Population trajectory ; Thyroperoxidase, Inhibition ; Thyroid hormone synthesis, Decreased ; Reduced, Swimming performance ; Reduced, Young of year survival ; Reduced, Anterior swim bladder inflation ; Reduced, Hearing

Decreased, Triiodothyronine (T3) in serum ; Inhibition, Deiodinase 1 ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis

Inhibition, Deiodinase 2 ; Decreased, Triiodothyronine (T3) in tissues ; Altered, Amphibian metamorphosis

Altered, Amphibian metamorphosis ; Inhibition, Deiodinase 3 ; Increased, Triiodothyronine (T3) in tissues

Increase, Mortality ; Decrease, Mitochondrial ATP production ; Increase, Apoptosis ; Increase, Uncoupling of oxidative phosphorylation

Decrease, Mitochondrial ATP production ; Decrease, Ovulation ; Decrease, Oogenesis ; Increase, Uncoupling of oxidative phosphorylation ; Decrease, Fecundity

Decrease, Mitochondrial ATP production ; Increase, Uncoupling of photophosphorylation ; Decrease, Chloroplast ATP production ; Decrease, Chlorophyll synthesis ; Decrease, Light harvest capacity ; Decrease, Photosynthesis ; Decrease, Glycolysis ; Decrease, Oxidative phosphorylation ; Decrease, Leaf cell mitosis ; Decrease, Leaf development ; Increase, Growth inhibition

Increased, Mortality ; Occurrence, renal proximal tubular necrosis ; Increased, blood potassium concentration ; Occurrence, cardiac arrhythmia ; Increased, Oxidative Stress ; Unknown, MIE ; Increased, Reactive oxygen species

Reduction, Plasma 17beta-estradiol concentrations ; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells ; Reduction, Vitellogenin synthesis in liver ; Reduction, Cumulative fecundity and spawning ; Reduction, Plasma vitellogenin concentrations ; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development ; Decrease, Population trajectory ; Increased, HIF-1 heterodimer ; Decreased, Aromatase (Cyp19a1) mRNA ; modulation, Unknown ; Increased, HIF-1 alpha transcription

Activation, Pregnane-X receptor, NR1l2 ; Thyroxine (T4) in neuronal tissue, Decreased ; Thyroxine (T4) in serum, Decreased ; Induction, Upregulation of glucuronyltransferase activity ; Increase, Biliary excretion TH glucuronide ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered ; Hippocampal gene expression, Altered ; Loss, Cochlear function

Increase, Urinary bladder calculi ; Increase, Cytotoxicity (urothelial cells) ; Increase, Regenerative cell proliferation (urothelial cells) ; Increase, Hyperplasia (urothelial) ; Increase, Adenomas/carcinomas (urothelial)

Abnormal, Foraging activity and behavior ; Weakened, Colony ; Death/Failure, Colony

Weakened, Colony ; Death/Failure, Colony ; Increased, Deformed Wing Virus levels

Binding to ER ; Nonspecific Protein Binding ; Binding to AR ; Binding to PR ; Binding to GR ; Binding to MR ; ER Transcription Factors ; Upreregulated Gene Transcription in the liver tissue ; Gene expression for Vtg production ; Alteration of Anal fin papillae ; Alteration of Gonadal morphology ; Reduced Growth ; Reduced eggs per female ; Reduced Fertility ; Mixed sex gonads ; Sex reversal ; Delayed adult mail mortality ; Altered sex ratios ; Population reduction

TRPA1 activation, TRPA1 Receptor ; TRPV1 activation, TRPV1 ; Activation of oxidative stress pathway ; Opening of calcium channel, Calcium influx ; Trigeminal nerve activation ; SP (Substance P) release, Local increase of SP ; Non-neuronal production of TNF, Epithelial irritation ; Immune system inflammation ; Production of nerve growth factor , Epithelial irritation ; Non-neuronal production of IL-8/CXCL1, Epithelial irritation ; Generation of novel epitopes , Antigen presentation ; Trigeminal and/or vagal nerve excitation causes Airway Hyper-responsiveness,Cough, Dyspnea ; Increased Respiratory irritability and Chronic Cough, ; Sensitization, Immune system ; Increase, hypertension ; Increased CGRP, neuronal release of CGRP ; Increased neurokinin A (NKA) by neuronal cells ; Irritation of nasal mucosa inducing sneeze reflex

Interaction with inner mitochondrial membrane & non-covalent perturbation ; Death ; Reduced ATP formation ; Inhibition of ATP-dependent cellular functions ; Reduced ATP-depndent functions ; Heart Failure ; Respiratory Failure ; Increased metabolism ; Population reduction

Abnormal, Foraging activity and behavior ; Weakened, Colony ; Death/Failure, Colony

Weakened, Colony ; Death/Failure, Colony

Inhibition, Inhibition of Dopamine-beta-hydroxylase ; Decreased, Synthesis of NE ; Decreased, GnRH cfos activity ; Decreased, GnRH pulsatility/release ; Decreased, LH Surge ; Delayed, Ovulation ; Decreased, Cortical granule release/distribution upon fertilization ; Altered, Formation of cortical envelope ; Abnormal, Sperm penetration (polyspermy) ; Altered, Chromosome number (polyploid) zygote ; Decreased, Decreased fecundity