Open main menu
Neurotoxins can be found in a number of organisms, including some strains of cyanobacteria,[1] that can be found in algal blooms or washed up on shore in a green scum.[2]

Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity).[3] Neurotoxins are an extensive class of exogenous chemical neurological insults[4] that can adversely affect function in both developing and mature nervous tissue.[5] The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic.[4] Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems.[6] Common examples of neurotoxins include lead,[7] ethanol (drinking alcohol),[8] glutamate,[9] nitric oxide,[10] botulinum toxin (e.g. Botox),[11] tetanus toxin,[12] and tetrodotoxin.[6] Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations.

Neurotoxins inhibit neuron control over ion concentrations across the cell membrane,[6] or communication between neurons across a synapse.[13] Local pathology of neurotoxin exposure often includes neuron excitotoxicity or apoptosis[14] but can also include glial cell damage.[15] Macroscopic manifestations of neurotoxin exposure can include widespread central nervous system damage such as intellectual disability,[5] persistent memory impairments,[16] epilepsy, and dementia.[17] Additionally, neurotoxin-mediated peripheral nervous system damage such as neuropathy or myopathy is common. Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant[8] and antitoxin[18] administration.



Illustration of typical multipolar neuron




Astrocytes surrounding capillaries in the brain to form the blood brain barrier


Choroid plexus

By being hydrophobic and small, or inhibiting astrocyte function, some compounds including certain neurotoxins are able to penetrate into the brain and induce significant damage. In modern times, scientists and physicians have been presented with the challenge of identifying and treating neurotoxins, which has resulted in a growing interest in both neurotoxicology research and clinical studies.[23] Though clinical neurotoxicology is largely a burgeoning field, extensive inroads have been made in the identification of many environmental neurotoxins leading to the classification of 750 to 1000 known potentially neurotoxic compounds.[20] Due to the critical importance of finding neurotoxins in common environments, specific protocols have been developed by the United States Environmental Protection Agency (EPA) for testing and determining neurotoxic effects of compounds (USEPA 1998). Additionally, in vitro systems have increased in use as they provide significant improvements over the more common in vivo systems of the past. Examples of improvements include tractable, uniform environments, and the elimination of contaminating effects of systemic metabolism.[23] In vitro systems, however, have presented problems as it has been difficult to properly replicate the complexities of the nervous system, such as the interactions between supporting astrocytes and neurons in creating the BBB.[24] To even further complicate the process of determining neurotoxins when testing in-vitro, neurotoxicity and cytotoxicity may be difficult to distinguish as exposing neurons directly to compounds may not be possible in-vivo, as it is in-vitro. Additionally, the response of cells to chemicals may not accurately convey a distinction between neurotoxins and cytotoxins, as symptoms like oxidative stress or skeletal modifications may occur in response to either.[25]

In an effort to address this complication, neurite outgrowths (either axonal or dendritic) in response to applied compounds have recently been proposed as a more accurate distinction between true neurotoxins and cytotoxins in an in-vitro testing environment. Due to the significant inaccuracies associated with this process, however, it has been slow in gaining widespread support.[26] Additionally, biochemical mechanisms have become more widely used in neurotoxin testing, such that compounds can be screened for sufficiency to induce cell mechanism interference, like the inhibition of acetylcholinesterase capacity of organophosphates (includes DDT and sarin gas).[27] Though methods of determining neurotoxicity still require significant development, the identification of deleterious compounds and toxin exposure symptoms has undergone significant improvement.

Applications in neuroscienceEdit

Though diverse in chemical properties and functions, neurotoxins share the common property that they act by some mechanism leading to either the disruption or destruction of necessary components within the nervous system. Neurotoxins, however, by their very design can be very useful in the field of neuroscience. As the nervous system in most organisms is both highly complex and necessary for survival, it has naturally become a target for attack by both predators and prey. As venomous organisms often use their neurotoxins to subdue a predator or prey very rapidly, toxins have evolved to become highly specific to their target channels such that the toxin does not readily bind other targets[28] (see Ion Channel toxins). As such, neurotoxins provide an effective means by which certain elements of the nervous system may be accurately and efficiently targeted. An early example of neurotoxin based targeting used radiolabeled tetrodotoxin to assay sodium channels and obtain precise measurements about their concentration along nerve membranes.[28] Likewise through isolation of certain channel activities, neurotoxins have provided the ability to improve the original Hodgkin-Huxley model of the neuron in which it was theorized that single generic sodium and potassium channels could account for most nervous tissue function.[28] From this basic understanding, the use of common compounds such as tetrodotoxin, tetraethylammonium, and bungarotoxins have led to a much deeper understanding of the distinct ways in which individual neurons may behave.

Mechanisms of activityEdit

As neurotoxins are compounds which adversely affect the nervous system, a number of mechanisms through which they function are through the inhibition of neuron cellular processes. These inhibited processes can range from membrane depolarization mechanisms to inter-neuron communication. By inhibiting the ability for neurons to perform their expected intracellular functions, or pass a signal to a neighboring cell, neurotoxins can induce systemic nervous system arrest as in the case of botulinum toxin,[13] or even nervous tissue death.[29] The time required for the onset of symptoms upon neurotoxin exposure can vary between different toxins, being on the order of hours for botulinum toxin[18] and years for lead.[30]

Neurotoxin classification Neurotoxins
Na channel inhibitors Tetrodotoxin[6]
K channel inhibitors Tetraethylammonium[31]
Cl channel inhibitors Chlorotoxin,[32]
Ca channel inhibitors Conotoxin[33]
Inhibitors of synaptic vesicle release Botulinum toxin,[34] tetanus toxin[35]
Receptor inhibitors Bungarotoxin[36]


Receptor agonists 25I-NBOMe[38]


Blood brain barrier inhibitors mercury[40]
Cytoskeleton interference Arsenic,[41] ammonia[42]
Ca-mediated cytotoxicity Lead[43]
Multiple effects Ethanol[44][45]
Endogenous neurotoxin sources Nitric oxide,[46] Glutamate,[47] Dopamine[48]


Sodium channelEdit

The puffer fish is known for carrying lethal amounts of tetrodotoxin.


Inhibited signaling response resulting from neuron exposure to tetrodotoxin.


Potassium channelEdit



Chloride channelEdit



Calcium channelEdit


Conotoxins represent a category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a number of ion channels such as calcium, sodium, or potassium channels.[57][58] In many cases, the toxins released by the different types of cone snails include a range of different types of conotoxins, which may be specific for different ion channels, thus creating a venom capable of widespread nerve function interruption.[57] One of the unique forms of conotoxins, ω-conotoxin (ω-CgTx) is highly specific for Ca channels and has shown usefulness in isolating them from a system.[59] As calcium flux is necessary for proper excitability of a cell, any significant inhibition could prevent a large amount of functionality. Significantly, ω-CgTx is capable of long term binding to and inhibition of voltage-dependent calcium channels located in the membranes of neurons but not those of muscle cells.[60]

Synaptic vesicle releaseEdit

Botulinum toxinEdit
Mechanism of Botulinum Toxin neurotoxicity

Botulinum Toxin (BTX) is a group of neurotoxins consisting of eight distinct compounds, referred to as BTX-A,B,C,D,E,F,G,H, which are produced by the bacterium Clostridium botulinum and lead to muscular paralysis.[61] A notably unique feature of BTX is its relatively common therapeutic use in treating dystonia and spasticity disorders,[61] as well as in inducing muscular atrophy[11] despite being the most poisonous substance known.[18] BTX functions peripherally to inhibit acetylcholine (ACh) release at the neuromuscular junction through degradation of the SNARE proteins required for ACh vesicle-membrane fusion.[34] As the toxin is highly biologically active, an estimated dose of 1μg/kg body weight is sufficient to induce an insufficient tidal volume and resultant death by asphyxiation.[13] Due to its high toxicity, BTX antitoxins have been an active area of research. It has been shown that capsaicin (active compound responsible for heat in chili peppers) can bind the TRPV1 receptor expressed on cholinergic neurons and inhibit the toxic effects of BTX.[18]

Tetanus toxinEdit

Tetanus neurotoxin (TeNT) is a compound that functionally reduces inhibitory transmissions in the nervous system resulting in muscular tetany. TeNT is similar to BTX, and is in fact highly similar in structure and origin; both belonging to the same category of clostridial neurotoxins.[12] Like BTX, TeNT inhibits inter-neuron communication by means of vesicular neurotransmitter (NT) release.[35] One notable difference between the two compounds is that while BTX inhibits muscular contractions, TeNT induces them. Though both toxins inhibit vesicle release at neuron synapses, the reason for this different manifestation is that BTX functions mainly in the peripheral nervous system (PNS) while TeNT is largely active in the central nervous system (CNS).[62] This is a result of TeNT migration through motor neurons to the inhibitory neurons of the spinal cord after entering through endocytosis.[63] This results in a loss of function in inhibitory neurons within the CNS resulting in systemic muscular contractions. Similar to the prognosis of a lethal dose of BTX, TeNT leads to paralysis and subsequent suffocation.[63]

Blood brain barrierEdit


Neurotoxic behavior of aluminum is known to occur upon entry into the circulatory system, where it can migrate to the brain and inhibit some of the crucial functions of the blood brain barrier (BBB).[64] A loss of function in the BBB can produce significant damage to the neurons in the CNS, as the barrier protecting the brain from other toxins found in the blood will no longer be capable of such action. Though the metal is known to be neurotoxic, effects are usually restricted to patients incapable of removing excess ions from the blood, such as those experiencing renal failure.[65] Patients experiencing aluminum toxicity can exhibit symptoms such as impaired learning and reduced motor coordination.[66] Additionally, systemic aluminum levels are known to increase with age, and have been shown to correlate with Alzheimer’s Disease, implicating it as a neurotoxic causative compound of the disease.[67] Despite its known toxicity, aluminum is still extensively utilized in the packaging and preparing of food, while other toxic metals such as lead have been almost entirely phased-out of use in these industries.



Receptor agonists and antagonistsEdit


External video
  Very Fast Death Factor
University of Nottingham

Investigations into anatoxin-a, also known as "Very Fast Death Factor", began in 1961 following the deaths of cows that drank from a lake containing an algal bloom in Saskatchewan, Canada.[70][71] It is a cyanotoxin produced by at least four different genera of cyanobacteria, and has been reported in North America, Europe, Africa, Asia, and New Zealand.[72]


When it was first discovered, the toxin was called the Very Fast Death Factor (VFDF) because when it was injected into the body cavity of mice it induced tremors, paralysis and death within a few minutes. In 1977, the structure of VFDF was determined as a secondary, bicyclic amine alkaloid, and it was renamed anatoxin-a.[75][76] Structurally, it is similar to cocaine.[77] There is continued interest in anatoxin-a because of the dangers it presents to recreational and drinking waters, and because it is a particularly useful molecule for investigating acetylcholine receptors in the nervous system.[78] The deadliness of the toxin means that it has a high military potential as a toxin weapon.[79]


Bungarotoxin is a compound with known interaction with nicotinic acetylcholine receptors (nAChRs), which constitute a family of ion channels whose activity is triggered by neurotransmitter binding.[80] Bungarotoxin is produced in a number of different forms, though one of the commonly used forms is the long chain alpha form, α-bungarotoxin, which is isolated from the banded krait snake.[36] Though extremely toxic if ingested, α-bungarotoxin has shown extensive usefulness in neuroscience as it is particularly adept at isolating nAChRs due to its high affinity to the receptors.[36] As there are multiple forms of bungarotoxin, there are different forms of nAChRs to which they will bind, and α-bungarotoxin is particularly specific for α7-nAChR.[81] This α7-nAChR functions to allow calcium ion influx into cells, and thus when blocked by ingested bungarotoxin will produce damaging effects, as ACh signaling will be inhibited.[81] Likewise, the use of α-bungarotoxin can be very useful in neuroscience if it is desirable to block calcium flux in order to isolate effects of other channels. Additionally, different forms of bungarotoxin may be useful for studying inhibited nAChRs and their resultant calcium ion flow in different systems of the body. For example, α-bungarotoxin is specific for nAChRs found in the musculature and κ-bungarotoxin is specific for nAChRs found in neurons.[82]


Caramboxin (CBX) is a toxin found in star fruit (Averrhoa carambola). Individuals with some types of kidney disease are susceptible to adverse neurological effects including intoxication, seizures and even death after eating star fruit or drinking juice made of this fruit. Caramboxin is a new nonpeptide amino acid toxin that stimulate the glutamate receptors in neurons. Caramboxin is an agonist of both NMDA and AMPA glutamatergic ionotropic receptors with potent excitatory, convulsant, and neurodegenerative properties.[83]


The term "curare" is ambiguous because it has been used to describe a number of poisons which at the time of naming were understood differently from present day understandings. In the past the characterization has meant poisons used by South American tribes on arrows or darts, though it has matured to specify a specific categorization of poisons which act on the neuromuscular junction to inhibit signaling and thus induce muscle relaxation.[84] The neurotoxin category contains a number of distinct poisons, though all were originally purified from plants originating in South America.[84] The effect with which injected curare poison is usually associated is muscle paralysis and resultant death.[85] Curare notably functions to inhibit nicotinic acetylcholine receptors at the neuromuscular junction. Normally, these receptor channels allow sodium ions into muscle cells to initiate an action potential that leads to muscle contraction. By blocking the receptors, the neurotoxin is capable of significantly reducing neuromuscular junction signaling, an effect which has resulted in its use by anesthesiologists to produce muscular relaxation.[86]

Cytoskeleton interferenceEdit


Arsenic is a neurotoxin commonly found concentrated in areas exposed to agricultural runoff, mining, and smelting sites (Martinez-Finley 2011). One of the effects of arsenic ingestion during the development of the nervous system is the inhibition of neurite growth[87] which can occur both in PNS and the CNS.[88] This neurite growth inhibition can often lead to defects in neural migration, and significant morphological changes of neurons during development,[89]) often leading to neural tube defects in neonates.[90] As a metabolite of arsenic, arsenite is formed after ingestion of arsenic and has shown significant toxicity to neurons within about 24 hours of exposure. The mechanism of this cytotoxicity functions through arsenite-induced increases in intracellular calcium ion levels within neurons, which may subsequently reduce mitochondrial transmembrane potential which activates caspases, triggering cell death.[89] Another known function of arsenite is its destructive nature towards the cytoskeleton through inhibition of neurofilament transport.[41] This is particularly destructive as neurofilaments are used in basic cell structure and support. Lithium administration has shown promise, however, in restoring some of the lost neurofilament motility.[91] Additionally, similar to other neurotoxin treatments, the administration of certain antioxidants has shown some promise in reducing neurotoxicity of ingested arsenic.[89]

An Astrocyte, a cell notable for maintaining the blood brain barrier

Ammonia toxicity is often seen through two routes of administration, either through consumption or through endogenous ailments such as liver failure.[92][93] One notable case in which ammonia toxicity is common is in response to cirrhosis of the liver which results in hepatic encephalopathy, and can result in cerebral edema (Haussinger 2006). This cerebral edema can be the result of nervous cell remodeling. As a consequence of increased concentrations, ammonia activity in-vivo has been shown to induce swelling of astrocytes in the brain through increased production of cGMP (Cyclic Guanosine Monophosphate) within the cells which leads to Protein Kinase G-mediated (PKG) cytoskeletal modifications.[42] The resultant effect of this toxicity can be reduced brain energy metabolism and function. Importantly, the toxic effects of ammonia on astrocyte remodeling can be reduced through administration of L-carnitine.[92] This astrocyte remodeling appears to be mediated through ammonia-induced mitochondrial permeability transition. This mitochondrial transition is a direct result of glutamine activity a compound which forms from ammonia in-vivo.[94] Administration of antioxidants or glutaminase inhibitor can reduce this mitochondrial transition, and potentially also astrocyte remodeling.[94]

Calcium-mediated cytotoxicityEdit

Lead pipes and solder are common sources of ingested lead.


Lead is a potent neurotoxin whose toxicity has been recognized for at least thousands of years.[95] Though neurotoxic effects for lead are found in both adults and young children, the developing brain is particularly susceptible to lead-induced harm, effects which can include apoptosis and excitotoxicity.[95] An underlying mechanism by which lead is able to cause harm is its ability to be transported by calcium ATPase pumps across the BBB, allowing for direct contact with the fragile cells within the central nervous system.[96] Neurotoxicity results from lead’s ability to act in a similar manner to calcium ions, as concentrated lead will lead to cellular uptake of calcium which disrupts cellular homeostasis and induces apoptosis.[43] It is this intracellular calcium increase that activates protein kinase C (PKC), which manifests as learning deficits in children as a result of early lead exposure.[43] In addition to inducing apoptosis, lead inhibits interneuron signaling through the disruption of calcium-mediated neurotransmitter release.[97]

Neurotoxins with multiple effectsEdit


As a neurotoxin, ethanol has been shown to induce nervous system damage and affect the body in a variety of ways. Among the known effects of ethanol exposure are both transient and lasting consequences. Some of the lasting effects include long-term reduced neurogenesis in the hippocampus,[98][99] widespread brain atrophy,[100] and induced inflammation in the brain.[101] Of note, chronic ethanol ingestion has additionally been shown to induce reorganization of cellular membrane constituents, leading to a lipid bilayer marked by increased membrane concentrations of cholesterol and saturated fat.[45] This is important as neurotransmitter transport can be impaired through vesicular transport inhibition, resulting in diminished neural network function. One significant example of reduced inter-neuron communication is the ability for ethanol to inhibit NMDA receptors in the hippocampus, resulting in reduced long-term potentiation (LTP) and memory acquisition.[44] NMDA has been shown to play an important role in LTP and consequently memory formation.[102] With chronic ethanol intake, however, the susceptibility of these NMDA receptors to induce LTP increases in the mesolimbic dopamine neurons in an inositol 1,4,5-triphosphate (IP3) dependent manner.[103] This reorganization may lead to neuronal cytotoxicity both through hyperactivation of postsynaptic neurons and through induced addiction to continuous ethanol consumption. It has, additionally, been shown that ethanol directly reduces intracellular calcium ion accumulation through inhibited NMDA receptor activity, and thus reduces the capacity for the occurrence of LTP.[104]

In addition to the neurotoxic effects of ethanol in mature organisms, chronic ingestion is capable of inducing severe developmental defects. Evidence was first shown in 1973 of a connection between chronic ethanol intake by mothers and defects in their offspring.[105] This work was responsible for creating the classification of fetal alcohol syndrome; a disease characterized by common morphogenesis aberrations such as defects in craniofacial formation, limb development, and cardiovascular formation. The magnitude of ethanol neurotoxicity in fetuses leading to fetal alcohol syndrome has been shown to be dependent on antioxidant levels in the brain such as vitamin E.[106] As the fetal brain is relatively fragile and susceptible to induced stresses, severe deleterious effects of alcohol exposure can be seen in important areas such as the hippocampus and cerebellum. The severity of these effects is directly dependent upon the amount and frequency of ethanol consumption by the mother, and the stage in development of the fetus.[107] It is known that ethanol exposure results in reduced antioxidant levels, mitochondrial dysfunction (Chu 2007), and subsequent neuronal death, seemingly as a result of increased generation of reactive oxidative species (ROS).[29] This is a plausible mechanism, as there is a reduced presence in the fetal brain of antioxidant enzymes such as catalase and peroxidase.[108] In support of this mechanism, administration of high levels of dietary vitamin E results in reduced or eliminated ethanol-induced neurotoxic effects in fetuses.[8]


n-Hexane is a neurotoxin which has been responsible for the poisoning of several workers in Chinese electronics factories in recent years.[109][110][111][112]

Receptor-selective neurotoxinsEdit


MPP+, the toxic metabolite of MPTP is a selective neurotoxin which interferes with oxidative phosphorylation in mitochondria by inhibiting complex I, leading to the depletion of ATP and subsequent cell death. This occurs almost exclusively in dopaminergic neurons of the substantia nigra, resulting in the presentation of permanent parkinsonism in exposed subjects 2–3 days after administration.

Endogenous neurotoxin sourcesEdit


Nitric oxideEdit





Dopamine is an endogenous compound that is used as a neurotransmitter to modulate reward expectation. Dopamine kills dopamine-producing neurons by interfering with the electron transport chain in neurons. This interference results in an inhibition of cellular respiration, leading to neuron death.

See alsoEdit


  1. ^ Sivonen, K (1999). "Toxins produced by cyanobacteria". Vesitalous. 5: 11–18.
  3. ^ Dorland's Medical Dictionary for Health Consumers
  4. ^ a b Spencer 2000
  5. ^ a b Olney 2002
  6. ^ a b c d e f g h Kiernan 2005
  7. ^ Lidsky 2003
  8. ^ a b c Heaton; Barrow, Marieta; Mitchell, J. Jean; Paiva, Michael (2000). "Amelioration of Ethanol-Induced Neurotoxicity in the Neonatal Rat Central Nervous System by Antioxidant Therapy". Alcoholism: Clinical and Experimental Research. 24 (4): 512–18. doi:10.1111/j.1530-0277.2000.tb02019.x.
  9. ^ a b c d Choi 1987
  10. ^ Zhang 1994
  11. ^ a b Rosales, Raymond L.; Arimura, Kimiyoshi; Takenaga, Satoshi; Osame, Mitsuhiro (1996). "Extrafusal and Intrafusal Muscle Effects in Experimental Botulinum Toxin-A Injection". Muscle & Nerve. 19 (4): 488–96. doi:10.1002/(sici)1097-4598(199604)19:4<488::aid-mus9>;2-8.
  12. ^ a b Simpson 1986
  13. ^ a b c Arnon 2001
  14. ^ Dikranian 2001
  15. ^ Deng 2003
  16. ^ Jevtovic-Todorovic 2003
  17. ^ Nadler 1978
  18. ^ a b c d Thyagarajan 2009
  19. ^ Hodge 2002
  20. ^ a b Dobbs 2009
  22. ^ a b Martini 2009
  23. ^ a b Costa 2011
  24. ^ Harry 1998
  25. ^ Gartlon 2006
  26. ^ Radio, Nicholas M.; Mundy, William R. (2008). "Developmental Neurotoxicity Testing in Vitro: Models for Assessing Chemical Effects on Neurite Out-growth". NeuroToxicology. 29 (3): 361–376. doi:10.1016/j.neuro.2008.02.011. PMID 18403021.
  27. ^ Lotti 2005
  28. ^ a b c Adams 2003
  29. ^ a b Brocardo 2011
  30. ^ Lewendon 2001
  31. ^ a b Haghdoost-Yazdi 2011
  32. ^ a b DeBin 1993
  33. ^ McClesky 1987
  34. ^ a b Garcia-Rodriguez 2011
  35. ^ a b Williamson 1996
  36. ^ a b c Dutertre 2006
  37. ^ Koller 1988
  38. ^ Rutgrere 2012
  39. ^ Roller 1994
  40. ^ a b c Aschner 1990
  41. ^ a b DeFuria 2006
  42. ^ a b Konopacka 2009
  43. ^ a b c Bressler 1999
  44. ^ a b Lovinger, D.; White, G.; Weight, F. (1989). "Ethanol Inhibits NMDA-activated Ion Current in Hippocampal Neurons". Science. 243 (4899): 1721–724. doi:10.1126/science.2467382. PMID 2467382.
  45. ^ a b Leonard, B. E. (1986). "Is Ethanol a Neurotoxin?: the Effects of Ethanol on Neuronal Structure and Function". Alcohol and Alcoholism. 21 (4): 325–38. doi:10.1093/oxfordjournals.alcalc.a044638.
  46. ^ a b Garthwaite 1988
  47. ^ a b c Choi 1990
  48. ^ Ben-Shachar D, Zuk R, Glinka Y (1995). "Dopamine neurotoxicity: inhibition of mitochondrial respiration". J. Neurochem. 64 (2): 718–23. doi:10.1046/j.1471-4159.1995.64020718.x. PMID 7830065.
  49. ^ a b c Chowdhury, F. R.; Ahasan, H A M. Nazmul; Rashid, A K M. Mamunur; Mamun, A. Al; Khaliduzzaman, S. M. (2007). "Tetrodotoxin Poisoning: a Clinical Analysis, Role of Neostigmine and Short-term Outcome of 53 Cases". Singapore Medical Journal. 48 (9): 830–33.
  50. ^ Ahasan 2004
  51. ^ Lau 1995
  52. ^ a b c Standfield 1983
  53. ^ Roed 1989
  54. ^ Haghdoost-Yasdi 2011
  55. ^ Deshane 2003
  56. ^ Soroceanu 1998
  57. ^ a b Jacob 2010
  58. ^ Olivera 1987
  59. ^ Cruz 1986
  60. ^ McCleskey 1987
  62. ^ Montecucco 1986
  63. ^ a b Pirazzini 2011
  64. ^ Banks 1988
  65. ^ King 1981
  66. ^ Rabe 1982
  67. ^ Walton 2006
  68. ^ Chan 2011
  69. ^ Brookes 1988
  70. ^ Carmichael 1978
  71. ^ Carmichael 1975
  72. ^ Yang 2007
  73. ^ Wood 2007
  74. ^ National Center for Environmental Assessment
  75. ^ Devlin 1977
  76. ^ Moore 1977
  77. ^ Metcalf 2009
  78. ^ Stewart 2008
  79. ^ Dixit 2005
  80. ^ Tsetlin 2003
  81. ^ a b Liu 2008
  82. ^ Hue 2007
  84. ^ a b Bisset 1992
  85. ^ Schlesinger 1946
  86. ^ Griffith, Harold R.; Johnson, G. Enid (1942). "The Use Of Curare In General Anesthesia". Anesthesiology. 3 (4): 418–420. doi:10.1097/00000542-194207000-00006.
  87. ^ Liu 2009
  88. ^ Vahidnia 2007
  89. ^ a b c Rocha 2011
  90. ^ Brender 2005
  91. ^ DeFuria 2007
  92. ^ a b Matsuoka 1991
  93. ^ Buzanska (2000)
  94. ^ a b Norenberg 2004
  95. ^ a b Lidskey 2003
  96. ^ Bradbury 1993
  97. ^ Lasley 1999
  98. ^ Taffe 2010
  99. ^ Morris 2009
  100. ^ Bleich 2003
  101. ^ Blanco 2005
  102. ^ Davis 1992
  103. ^ Bernier 2011
  104. ^ Takadera 1990
  105. ^ Jones 1973
  106. ^ Mitchell 1999
  107. ^ Gil-Mohapel 2010
  108. ^ Bergamini 2004
  109. ^ Workers poisoned while making iPhones ABC News, October 25, 2010
  110. ^ Dirty Secrets Archived 2017-05-25 at the Wayback Machine ABC Foreign Correspondent, 2010-Oct-26
  112. ^ Occupational Safety and Health Guideline for n-Hexane Archived 2011-12-18 at the Wayback Machine,
  113. ^ Iadecola 1998
  114. ^ Beckman 1990
  115. ^ Bonfoco 1995


Further readingEdit

External linksEdit