Mechanisms and modes of β-N-methylamino-lalanine neurotoxicity: the basis for designing therapies
- Authors: Van Onselen, Rianita
- Date: 2019
- Subjects: Cyanobacteria , Amino acids -- Toxicology , Neurotoxic agents
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/32971 , vital:32483
- Description: Since the discovery of the non-canonical amino acid β-N-methylamino-L-alanine (BMAA) and the demonstration of its acute neurotoxicity in chicks and rats, it has been postulated that BMAA might contribute to the development of neurodegenerative diseases worldwide due to its presence in numerous aquatic and terrestrial food webs. This hypothesized link was widely criticized because of the inability to reproduce symptoms in a BMAA-exposed animal model that resembled the symptoms observed in humans, and for the inability to achieve significant levels of toxicity in in vitro models via the postulated mechanisms of toxicity. The most widely described mechanism of BMAA toxicity was excitotoxicity by over-excitation of ionotropic and/or metabotropic glutamate receptors following activation by BMAA. However, the excitotoxic potency of BMAA is much lower than those of other known excitotoxins and it was not known whether BMAA could accumulate in significant concentrations in synapses to cause the said excitotoxicity. Therefore, uptake of BMAA into synaptic vesicles from where it can be released into synapses in high concentrations, was investigated and it was found that, unlike the uptake that was observed for glutamate, BMAA was not taken up into synaptic vesicles. This discovery suggests that BMAA is not released into synapses via synaptic vesicles and that excitotoxicity is an unlikely mechanism of BMAA toxicity in mammalian systems. Misincorporation of BMAA into proteins in the place of L-serine was suggested to be an important mechanism of BMAA toxicity that could lead to protein misfolding and the subsequent protein aggregates that are typically found in the central nervous system (CNS) of neurodegenerative disease patients. However, previous studies in prokaryotes and in a rat pheochromocytoma PC12 cell line showed that misincorporation of BMAA does not occur to any significant extent. However, these studies were criticized for not using human-derived model systems to show that misincorporation does not occur, and it was argued that due to differences in mitochondrial protein synthesis mechanisms, misincorporation of BMAA into human proteins could not be ruled out as a possible mechanism of toxicity. Therefore, misincorporation of BMAA was investigated in a number of human-derived non-neuronal cell lines and directly compared to the misincorporation of other known amino acid analogues. No evidence of misincorporation of BMAA into these cell lines was obtained and therefore it was concluded that misincorporation of BMAA into proteins does not occur in human-derived cell models. Although misincorporation of BMAA into proteins was refuted as a mechanism of toxicity, the strong interactions between BMAA and proteins that require extensive purification procedures to remove the associated BMAA, could not be discounted as a possible contributor to the toxicity of BMAA. Cell-free interactions between BMAA and enzymes, which resulted in reduced activity, were described previously but the nature of these interactions was never determined. Therefore, the direct interactions between BMAA and a range of commercial proteins and melanin (that is known to also have a strong affinity for BMAA) were investigated in an attempt to describe the nature of these interactions. It was discovered that BMAA has a high affinity for hydroxyl groups, and that if these hydroxyl groups in the form of hydroxyl containing amino acid residues occurred in important regulatory or active sites of proteins, BMAA reduced the enzyme activity. Catalase was subsequently selected as an important enzyme required for the maintenance of the delicate reactive oxygen species (ROS) balance in the CNS, to test the effect of BMAA on the activity of the enzyme. BMAA inhibited a human commercial extract of catalase in a cell free system, and this inhibition appeared to be non-competitive in nature. Subsequently, catalase in an extract from a human cell line was also shown to be inhibited by BMAA and it was concluded that this BMAA induced inhibition of catalase could be an important contributor to the toxicity of BMAA in in vivo systems. The affinity of BMAA for hydroxyl groups, especially the reactive L-tyrosine side chain hydroxyl, was recognized as a possible mechanism that can be utilized to protect against the toxicity of BMAA. It was subsequently shown that excess concentrations of L-serine and L-tyrosine could protect against the BMAA-induced enzyme inhibition and improper folding of proteins in a cell-free system. By administering an equimolar concentration of either L-phenylalanine (the soluble precursor of L-tyrosine) or L-serine an hour before administration of BMAA in a rat model, the BMAA-induced neurotoxicity was greatly reduced, especially by treatment with L-phenylalanine, which resulted in a decrease of between 60-70% in the observed neuropathologies. It was recognized that the protection offered by L-phenylalanine was greater than would be expected if protection was by virtue of direct hydroxyl binding alone and it was subsequently hypothesized that the conversion of L-phenylalanine to dopamine could have contributed to the observed protection. Subsequently, the possible protection offered by dopamine, administered as L-DOPA, against BMAA neurotoxicity was investigated in the same neonatal rat model and compared to the protection offered by L-tyrosine. It was discovered that dopamine protected against the BMAAinduced neuronal cell losses in the hippocampus, striatum and spinal cord but it was not as efficient as L-tyrosine in protection against the BMAA-induced proteinopathies, suggesting two distinct mechanisms of BMAA toxicity, one of which is a depletion of dopamine, which had not been previously described. Finally, the nature of the BMAA-induced dopamine depletion was investigated by administering BMAA in combination with other dopaminergic modifiers viz. apomorphine (a D1/D2 receptor agonist), a dopamine transporter inhibitor (GBR12783) and reserpine (a vesicular monoamine transporter -VMAT2- inhibitor) to the neonatal rat model in an attempt to describe how BMAA functions as a dopaminergic toxin. Based on these results it was concluded that BMAA inhibits uptake of dopamine into synaptic vesicles by inhibiting VMAT2-mediated uptake of dopamine, which causes neuronal loss in the hippocampus, striatum and substantia nigra pars compacta, and that the BMAA-induced inhibition of catalase contributes significantly to the toxicity of BMAA by causing an accumulation of hydrogen peroxide in the hippocampus, striatum and spinal cord, which results in extensive neuronal damage in these areas. This work was the first to thoroughly investigate the mechanisms that explain the observed pathologies caused by BMAA in an in vivo model, and was the first to suggest that BMAA can reduce the dopamine in the CNS by inhibiting VMAT2-mediated uptake of dopamine into synaptic vesicles, and increase damage by reactive oxygen species by inhibiting catalase. BMAA is therefore a multimechanistic and multimodal.
- Full Text:
- Date Issued: 2019
- Authors: Van Onselen, Rianita
- Date: 2019
- Subjects: Cyanobacteria , Amino acids -- Toxicology , Neurotoxic agents
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/32971 , vital:32483
- Description: Since the discovery of the non-canonical amino acid β-N-methylamino-L-alanine (BMAA) and the demonstration of its acute neurotoxicity in chicks and rats, it has been postulated that BMAA might contribute to the development of neurodegenerative diseases worldwide due to its presence in numerous aquatic and terrestrial food webs. This hypothesized link was widely criticized because of the inability to reproduce symptoms in a BMAA-exposed animal model that resembled the symptoms observed in humans, and for the inability to achieve significant levels of toxicity in in vitro models via the postulated mechanisms of toxicity. The most widely described mechanism of BMAA toxicity was excitotoxicity by over-excitation of ionotropic and/or metabotropic glutamate receptors following activation by BMAA. However, the excitotoxic potency of BMAA is much lower than those of other known excitotoxins and it was not known whether BMAA could accumulate in significant concentrations in synapses to cause the said excitotoxicity. Therefore, uptake of BMAA into synaptic vesicles from where it can be released into synapses in high concentrations, was investigated and it was found that, unlike the uptake that was observed for glutamate, BMAA was not taken up into synaptic vesicles. This discovery suggests that BMAA is not released into synapses via synaptic vesicles and that excitotoxicity is an unlikely mechanism of BMAA toxicity in mammalian systems. Misincorporation of BMAA into proteins in the place of L-serine was suggested to be an important mechanism of BMAA toxicity that could lead to protein misfolding and the subsequent protein aggregates that are typically found in the central nervous system (CNS) of neurodegenerative disease patients. However, previous studies in prokaryotes and in a rat pheochromocytoma PC12 cell line showed that misincorporation of BMAA does not occur to any significant extent. However, these studies were criticized for not using human-derived model systems to show that misincorporation does not occur, and it was argued that due to differences in mitochondrial protein synthesis mechanisms, misincorporation of BMAA into human proteins could not be ruled out as a possible mechanism of toxicity. Therefore, misincorporation of BMAA was investigated in a number of human-derived non-neuronal cell lines and directly compared to the misincorporation of other known amino acid analogues. No evidence of misincorporation of BMAA into these cell lines was obtained and therefore it was concluded that misincorporation of BMAA into proteins does not occur in human-derived cell models. Although misincorporation of BMAA into proteins was refuted as a mechanism of toxicity, the strong interactions between BMAA and proteins that require extensive purification procedures to remove the associated BMAA, could not be discounted as a possible contributor to the toxicity of BMAA. Cell-free interactions between BMAA and enzymes, which resulted in reduced activity, were described previously but the nature of these interactions was never determined. Therefore, the direct interactions between BMAA and a range of commercial proteins and melanin (that is known to also have a strong affinity for BMAA) were investigated in an attempt to describe the nature of these interactions. It was discovered that BMAA has a high affinity for hydroxyl groups, and that if these hydroxyl groups in the form of hydroxyl containing amino acid residues occurred in important regulatory or active sites of proteins, BMAA reduced the enzyme activity. Catalase was subsequently selected as an important enzyme required for the maintenance of the delicate reactive oxygen species (ROS) balance in the CNS, to test the effect of BMAA on the activity of the enzyme. BMAA inhibited a human commercial extract of catalase in a cell free system, and this inhibition appeared to be non-competitive in nature. Subsequently, catalase in an extract from a human cell line was also shown to be inhibited by BMAA and it was concluded that this BMAA induced inhibition of catalase could be an important contributor to the toxicity of BMAA in in vivo systems. The affinity of BMAA for hydroxyl groups, especially the reactive L-tyrosine side chain hydroxyl, was recognized as a possible mechanism that can be utilized to protect against the toxicity of BMAA. It was subsequently shown that excess concentrations of L-serine and L-tyrosine could protect against the BMAA-induced enzyme inhibition and improper folding of proteins in a cell-free system. By administering an equimolar concentration of either L-phenylalanine (the soluble precursor of L-tyrosine) or L-serine an hour before administration of BMAA in a rat model, the BMAA-induced neurotoxicity was greatly reduced, especially by treatment with L-phenylalanine, which resulted in a decrease of between 60-70% in the observed neuropathologies. It was recognized that the protection offered by L-phenylalanine was greater than would be expected if protection was by virtue of direct hydroxyl binding alone and it was subsequently hypothesized that the conversion of L-phenylalanine to dopamine could have contributed to the observed protection. Subsequently, the possible protection offered by dopamine, administered as L-DOPA, against BMAA neurotoxicity was investigated in the same neonatal rat model and compared to the protection offered by L-tyrosine. It was discovered that dopamine protected against the BMAAinduced neuronal cell losses in the hippocampus, striatum and spinal cord but it was not as efficient as L-tyrosine in protection against the BMAA-induced proteinopathies, suggesting two distinct mechanisms of BMAA toxicity, one of which is a depletion of dopamine, which had not been previously described. Finally, the nature of the BMAA-induced dopamine depletion was investigated by administering BMAA in combination with other dopaminergic modifiers viz. apomorphine (a D1/D2 receptor agonist), a dopamine transporter inhibitor (GBR12783) and reserpine (a vesicular monoamine transporter -VMAT2- inhibitor) to the neonatal rat model in an attempt to describe how BMAA functions as a dopaminergic toxin. Based on these results it was concluded that BMAA inhibits uptake of dopamine into synaptic vesicles by inhibiting VMAT2-mediated uptake of dopamine, which causes neuronal loss in the hippocampus, striatum and substantia nigra pars compacta, and that the BMAA-induced inhibition of catalase contributes significantly to the toxicity of BMAA by causing an accumulation of hydrogen peroxide in the hippocampus, striatum and spinal cord, which results in extensive neuronal damage in these areas. This work was the first to thoroughly investigate the mechanisms that explain the observed pathologies caused by BMAA in an in vivo model, and was the first to suggest that BMAA can reduce the dopamine in the CNS by inhibiting VMAT2-mediated uptake of dopamine into synaptic vesicles, and increase damage by reactive oxygen species by inhibiting catalase. BMAA is therefore a multimechanistic and multimodal.
- Full Text:
- Date Issued: 2019
The metabolism and environmental fate of the cyanobacterial neurotoxin Beta-N-methylamino-L-alanine
- Authors: Downing, Simoné
- Date: 2015
- Subjects: Cyanobacteria , Neurotoxic agents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/4225 , vital:20569
- Description: The neurotoxic amino acid β-‐N-‐methylamino-Lalanine (BMAA)is present in environmentally ubiquitous cyanobacteria and bioaccumulates and biomagnifies within the environment. The implication of BMAA in the development of neurodegenerative disease has raised concerns over the potential risk of human exposure to this neurotoxin, and has focussed attention on identifying possible routes of exposure that include direct contact with cyanobacteria and the ingestion of BMAA-‐containing plant and animal products.
- Full Text:
- Date Issued: 2015
- Authors: Downing, Simoné
- Date: 2015
- Subjects: Cyanobacteria , Neurotoxic agents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/4225 , vital:20569
- Description: The neurotoxic amino acid β-‐N-‐methylamino-Lalanine (BMAA)is present in environmentally ubiquitous cyanobacteria and bioaccumulates and biomagnifies within the environment. The implication of BMAA in the development of neurodegenerative disease has raised concerns over the potential risk of human exposure to this neurotoxin, and has focussed attention on identifying possible routes of exposure that include direct contact with cyanobacteria and the ingestion of BMAA-‐containing plant and animal products.
- Full Text:
- Date Issued: 2015
Potential for human exposure to Beta-N-methylamino-L-alanine in a freshwater system
- Authors: Scott, Laura Louise
- Date: 2014
- Subjects: Water quality biological assessment , Cyanobacteria , Neurotoxic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/5159 , vital:20816
- Description: β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid associated with human neurodegenerative diseases. The content of BMAA in cyanobacteria is modulated by nitrogen in laboratory cultures. In order to evaluate the potential for human exposure, the nitrogen modulation of BMAA content needed verification in a natural environment. In accordance with laboratory culture studies, data presented in this study show that combined nitrogen was the most significant modulator of both cellular microcystin (MC) and BMAA content in phytoplankton in an environmental cyanobacterial bloom. While BMAA is produced upon nitrogen deprivation, MC is only produced at a specific nitrogen threshold where the rate of increase of nitrogen in the cell exceeds the carbon fixation rate. As BMAA and MC were detected in phytoplankton sourced from the Hartbeespoort Dam reservoir, the transfer of these cyanotoxins to organisms of higher trophic levels was investigated. Both BMAA and MC were detected at high concentrations in the liver and muscle tissue of fish sourced from the Hartbeespoort Dam reservoir indicating that consumption of fish from this reservoir constitutes a serious risk of exposure to cyanotoxins. In addition to the dietary exposure route to BMAA, two recent studies reported a correlation between Amyotrophic Lateral Sclerosis (ALS) incidence and the potential for aerosol exposure to cyanobacteria. With the absence of any evidence of the systemic distribution of BMAA following inhalation, an evaluation of the potential exposure risk associated with living in close proximity to this reservoir was deemed premature. A laboratory experiment investigating the effect and systemic fate of inhaled aerosolised BMAA was therefore conducted in order to determine the feasibility of inhalation as a potential BMAA exposure route. Data from the rat inhalation exposure study, however, showed that in rats BMAA inhalation may not constitute a significant mechanism of toxicity at environmental BMAA levels.
- Full Text:
- Date Issued: 2014
- Authors: Scott, Laura Louise
- Date: 2014
- Subjects: Water quality biological assessment , Cyanobacteria , Neurotoxic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/5159 , vital:20816
- Description: β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid associated with human neurodegenerative diseases. The content of BMAA in cyanobacteria is modulated by nitrogen in laboratory cultures. In order to evaluate the potential for human exposure, the nitrogen modulation of BMAA content needed verification in a natural environment. In accordance with laboratory culture studies, data presented in this study show that combined nitrogen was the most significant modulator of both cellular microcystin (MC) and BMAA content in phytoplankton in an environmental cyanobacterial bloom. While BMAA is produced upon nitrogen deprivation, MC is only produced at a specific nitrogen threshold where the rate of increase of nitrogen in the cell exceeds the carbon fixation rate. As BMAA and MC were detected in phytoplankton sourced from the Hartbeespoort Dam reservoir, the transfer of these cyanotoxins to organisms of higher trophic levels was investigated. Both BMAA and MC were detected at high concentrations in the liver and muscle tissue of fish sourced from the Hartbeespoort Dam reservoir indicating that consumption of fish from this reservoir constitutes a serious risk of exposure to cyanotoxins. In addition to the dietary exposure route to BMAA, two recent studies reported a correlation between Amyotrophic Lateral Sclerosis (ALS) incidence and the potential for aerosol exposure to cyanobacteria. With the absence of any evidence of the systemic distribution of BMAA following inhalation, an evaluation of the potential exposure risk associated with living in close proximity to this reservoir was deemed premature. A laboratory experiment investigating the effect and systemic fate of inhaled aerosolised BMAA was therefore conducted in order to determine the feasibility of inhalation as a potential BMAA exposure route. Data from the rat inhalation exposure study, however, showed that in rats BMAA inhalation may not constitute a significant mechanism of toxicity at environmental BMAA levels.
- Full Text:
- Date Issued: 2014
Beta-N-methylamino-L-alanine in South African fresh water cyanobacteria : incidence, prevalence, ecotoxicological considerations and human exposure risk
- Authors: Esterhuizen-Londt, Maranda
- Date: 2010
- Subjects: Cyanobacteria , Bioaccumulation , Chromatographic analysis , Neurotoxic agents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10306 , http://hdl.handle.net/10948/1473 , Cyanobacteria , Bioaccumulation , Chromatographic analysis , Neurotoxic agents
- Description: β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid associated with human neurodegenerative disease. Due to the cosmopolitan nature of cyanobacteria, detection of BMAA in cyanobacteria has caused concerns about human exposure risk. This study was therefore based on the hypothesis that BMAA poses a health risk to humans either by direct ingestion or by indirect exposure to BMAA from a cyanobacterial source via a freshwater food chain. A validated gas chromatography-mass spectrometry (GC-MS) BMAA analysis method and a confirmatory liquid chromatography-mass spectrometry (LC-MS) method, with improved sensitivity, were developed in addition to a LC-MS/MS method for analyte confirmation. These methods were used to quantify BMAA in South African cyanobacteria, isolated from various potable water reservoirs. The majority of the isolates tested, contained BMAA. Possible human exposure by direct consumption of BMAA released from cyanobacterial blooms was investigated by the development of a robust solid phase extraction (SPE) method used for BMAA concentration and quantification in raw and treated tap water. Despite the use of the SPE method that facilitated the concentration of BMAA from large quantities of water, no free dissolved BMAA was detected in raw or processed fresh water. The fate of exogenous BMAA was therefore investigated firstly by evaluating the efficacy of standard water treatment processes employed in South Africa and secondly by investigating the possibility of BMAA bioaccumulation and biomagnification in aquatic food chains. Standard water treatment processes proved highly efficient at removing free dissolved BMAA, explaining the absence of BMAA in treated tap water. However, the cause of the BMAA absence in raw potable water remained unknown. Uptake of BMAA by model aquatic organisms was investigated in controlled experiments. BMAA uptake was documented in both Ceratophyllum demersum and Daphnia magna, however, BMAA-protein association and biomagnification were not observed in D. magna. BMAA had an inhibitory effect on the oxidative stress enzyme acitivties of both organisms tested (as well as human S9 extracts), resulting in accumulation of detrimental reactive oxygen species (ROS) in the cells. Exposure of crop plants to BMAA in controlled experiments resulted in BMAA uptake, protein association, and subsequent inhibition of the antioxidative enzyme activities. However, BMAA was detected in neither free nor protein-associated form in natural crop plants irrigated with known BMAA-containing bloom water. Post-mortem liver samples of Clarias gariepinus (Catfish) and Crocodylus niloticus (Crocodile), from a natural fresh water ecosystem that experienced frequent cyanobacterial blooms, contained both free and protein-associated BMAA. Higher BMAA concentrations were found in crocodile liver samples compared to fish liver samples, strongly suggesting biomagnification from one trophic level to the next. BMAA concentrations corresponded to crocodile age. This is the first report of bioaccumulation and biomagnification in two trophic levels in a fresh water ecosystem. These findings strongly suggest possible human exposure via aquatic food chains of cyanobacterial origin. Direct BMAA exposure via drinking water is not plausible due to the efficiency of standard water treatment processes to remove BMAA. The use of raw water for agricultural and recreational use, however, remains a problem. The development of management strategies as well as daily tolerable levels for BMAA is urgently required.
- Full Text:
- Date Issued: 2010
- Authors: Esterhuizen-Londt, Maranda
- Date: 2010
- Subjects: Cyanobacteria , Bioaccumulation , Chromatographic analysis , Neurotoxic agents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10306 , http://hdl.handle.net/10948/1473 , Cyanobacteria , Bioaccumulation , Chromatographic analysis , Neurotoxic agents
- Description: β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid associated with human neurodegenerative disease. Due to the cosmopolitan nature of cyanobacteria, detection of BMAA in cyanobacteria has caused concerns about human exposure risk. This study was therefore based on the hypothesis that BMAA poses a health risk to humans either by direct ingestion or by indirect exposure to BMAA from a cyanobacterial source via a freshwater food chain. A validated gas chromatography-mass spectrometry (GC-MS) BMAA analysis method and a confirmatory liquid chromatography-mass spectrometry (LC-MS) method, with improved sensitivity, were developed in addition to a LC-MS/MS method for analyte confirmation. These methods were used to quantify BMAA in South African cyanobacteria, isolated from various potable water reservoirs. The majority of the isolates tested, contained BMAA. Possible human exposure by direct consumption of BMAA released from cyanobacterial blooms was investigated by the development of a robust solid phase extraction (SPE) method used for BMAA concentration and quantification in raw and treated tap water. Despite the use of the SPE method that facilitated the concentration of BMAA from large quantities of water, no free dissolved BMAA was detected in raw or processed fresh water. The fate of exogenous BMAA was therefore investigated firstly by evaluating the efficacy of standard water treatment processes employed in South Africa and secondly by investigating the possibility of BMAA bioaccumulation and biomagnification in aquatic food chains. Standard water treatment processes proved highly efficient at removing free dissolved BMAA, explaining the absence of BMAA in treated tap water. However, the cause of the BMAA absence in raw potable water remained unknown. Uptake of BMAA by model aquatic organisms was investigated in controlled experiments. BMAA uptake was documented in both Ceratophyllum demersum and Daphnia magna, however, BMAA-protein association and biomagnification were not observed in D. magna. BMAA had an inhibitory effect on the oxidative stress enzyme acitivties of both organisms tested (as well as human S9 extracts), resulting in accumulation of detrimental reactive oxygen species (ROS) in the cells. Exposure of crop plants to BMAA in controlled experiments resulted in BMAA uptake, protein association, and subsequent inhibition of the antioxidative enzyme activities. However, BMAA was detected in neither free nor protein-associated form in natural crop plants irrigated with known BMAA-containing bloom water. Post-mortem liver samples of Clarias gariepinus (Catfish) and Crocodylus niloticus (Crocodile), from a natural fresh water ecosystem that experienced frequent cyanobacterial blooms, contained both free and protein-associated BMAA. Higher BMAA concentrations were found in crocodile liver samples compared to fish liver samples, strongly suggesting biomagnification from one trophic level to the next. BMAA concentrations corresponded to crocodile age. This is the first report of bioaccumulation and biomagnification in two trophic levels in a fresh water ecosystem. These findings strongly suggest possible human exposure via aquatic food chains of cyanobacterial origin. Direct BMAA exposure via drinking water is not plausible due to the efficiency of standard water treatment processes to remove BMAA. The use of raw water for agricultural and recreational use, however, remains a problem. The development of management strategies as well as daily tolerable levels for BMAA is urgently required.
- Full Text:
- Date Issued: 2010
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