Distribution of tritiated dihydromicrocystin in swine

Stotts, Richard R.; Twardock, A.R.; Haschek, Wanda M.; Choi, Byoung Wook; Rinehart, Kenneth L.; Beasley, Val R.

doi:10.1016/s0041-0101(96)00169-9

Cited by 22 publications

(14 citation statements)

References 26 publications

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“…A high degree of uncertainty remains as to the sufficiency of the uncertainty factors applied during extrapolation from animals to humans (factor 10), when considering the observed species (human-animal) differences in organic anion transporter profile (Fischer et al, 2004) and hence kinetic and dynamic dissimilarities (Batista et al, 2003). Although most acute and subchronic animal experiments have reported primarily liver pathology, some have also demonstrated nephropathy Milutinovic et al, 2002;Miura et al, 1991;Nobre et al, 1999;Stotts et al, 1997), while the potential occurrence of neuropathy has largely been ignored, despite clinical indications in the Caruaru incident (Azevedo et al, 2002;Fischer et al, 2004;Pouria et al, 1998). The question remains to be resolved whether the endpoint for the pivotal study for human risk assessment should only include chronic liver injury (Falconer et al, 1994;Fawell et al, 1994Fawell et al, , 1999 or the presence of preneoplastic lesions (Charbonneau et al, 2004), or whether indeed the development of an improved data base including nephropathy and neuropathy is more advisable.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the analysis of MC metabolism has demonstrated that MCs are primarily conjugated and then excreted either as parent compound or conjugate via the bile or the urine (Dahlem et al, 1989;Falconer et al, 1986;Hermansky et al, 1991;Kondo et al, 1992;Milutinovic et al, 2002;Nishiwaki et al, 1994;Robinson et al, 1989Robinson et al, , 1991Takenaka, 2001), probably involving the same organic anion transport proteins. Of importance is also that after moderate liver damage, for example, in MC-LR-dosed pigs, a reduced MC-LR clearance can be observed in the blood, resulting in an extended availability of MC-LR for uptake into other organs such as the kidneys (Stotts et al, 1997). Consequently, pathological changes are observed in those organs.…”

Section: Microcystins: Organ Specificity/distribution and Eliminationmentioning

confidence: 99%

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Guidance values for microcystins in water and cyanobacterial supplement products (blue-green algal supplements): a reasonable or misguided approach?

Dietrich

Hoeger

2005

Toxicology and Applied Pharmacology

325

185

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This article reviews current scientific knowledge on the toxicity and carcinogenicity of microcystins and compares this to the guidance values proposed for microcystins in water by the World Health Organization, and for blue-green algal food supplements by the Oregon State Department of Health. The basis of the risk assessment underlying these guidance values is viewed as being critical due to overt deficiencies in the data used for its generation: (i) use of one microcystin congener only (microcystin-LR), while the other presently known nearly 80 congeners are largely disregarded, (ii) new knowledge regarding potential neuro and renal toxicity of microcystins in humans and (iii) the inadequacies of assessing realistic microcystin exposures in humans and especially in children via blue-green algal food supplements. In reiterating the state-of-the-art toxicology database on microcystins and in the light of new data on the high degree of toxin contamination of algal food supplements, this review clearly demonstrates the need for improved kinetic data of microcystins in humans and for discussion concerning uncertainty factors, which may result in a lowering of the present guidance values and an increased routine control of water bodies and food supplements for toxin contamination. Similar to the approach taken previously by authorities for dioxin or PCB risk assessment, the use of a toxin equivalent approach to the risk assessment of microcystins is proposed. D

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Section: Discussionmentioning

confidence: 99%

Section: Microcystins: Organ Specificity/distribution and Eliminationmentioning

confidence: 99%

Guidance values for microcystins in water and cyanobacterial supplement products (blue-green algal supplements): a reasonable or misguided approach?

Dietrich

Hoeger

2005

Toxicology and Applied Pharmacology

325

185

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“…Despite that microcystins have generally been characterized as hepatotoxins, there is also evidence for neurotoxicity, as suggested in the Caruaru incident, where more than 60 dialysis patients died following i.v. treatment with MC contaminated dialysis water (Azevedo et al 2002;Fischer et al 2005;Jochimsen et al 1998;Pouria et al 1998), and for nephrotoxicity, as indicated by several animal experiments (Bhattacharya et al 1997;Fischer and Dietrich 2000;Khan et al Chapter 39: Toxin mixture in cyanobacterial blooms -a critical comparison of reality with current procedures employed in human health risk assessment 13 1996; Milutinovic et al 2002;Milutinovic et al 2003;Moreno et al 2005;Stotts et al 1997). Studies on organ distribution support these findings and suggest that, beside liver and kidney, the brain and the lungs (Picanco et al 2004) can also be affected to a varying extent Meriluoto et al 1990;Pace et al 1990;Robinson et al 1989;Robinson et al 1991;Stotts et al 1997).…”

Section: Human Health Risk Assessment Single Vs Multiple Compounds: mentioning

confidence: 99%

Toxin mixture in cyanobacterial blooms – a critical comparison of reality with current procedures employed in human health risk assessment

Dietrich¹,

Fischer²,

Michel³

et al.

Advances in Experimental Medicine and Biology

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Cyanobacteria are the oldest life forms on earth known to produce a broad spectrum of secondary metabolites. The functions/advantages of most of these secondary metabolites (peptides and alkaloids) are unknown, however, some of them have adverse effects in humans and wildlife, especially when ingested, inhaled or upon dermal exposure. Surprisingly, some of these cyanobacteria are ingested voluntarily. Indeed, for centuries mankind has used cyanobacteria as a protein source, primarily Spirulina species. However, recently also Aphanizomenon flos-aquae are used for the production of so called blue green algae supplements (BGAS), supposedly efficacious for treatment of various diseases and afflictions. Unfortunately, traces of neurotoxins and protein phosphatases (inhibiting compounds) have been detected in BGAS, making these health supplements a good example for human exposure to a mixture of cyanobacterial toxins in a complex matrix. The discussion of this and other possible exposure scenarios, e.g. drinking water, contact during recreational activity, or consumption of contaminated food, can provide insight into the question of whether or not our current risk assessment schemes for cyanobacterial blooms and the toxins contained therein suffice for protection of human health. Cyanobacterial metabolites: Health hazards for humans?Cyanobacteria exist worldwide ubiquitously, including in extreme environments (Hitzfeld et al.

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“…Fish kills have been reported in conjunction with cyanobacterial blooms and have often resulted in significant economic losses (43)(44)(45)(46)(47). The liver is the major target organ for microcystin toxicity; it was shown to accumulate 20-70% of a radioactively labeled toxin dose (intravenous) (48)(49)(50)(51)(52)(53)(54). Studies in mice and pigs exposed to extracts of a toxic M. aeruginosa bloom demonstrated dosedependent toxicity (55,56).…”

Section: Cylindrospermopsinmentioning

confidence: 99%

Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment.

Hitzfeld

Höger

Dietrich

2000

Environ Health Perspect

255

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Cyanobacteria (blue-green algae) produce toxins that may present a hazard for drinking water safety. These toxins (microcystins, nodularins, saxitoxins, anatoxin-a, anatoxin-a(s), cylindrospermopsin) are structurally diverse and their effects range from liver damage, including liver cancer, to neurotoxicity. The occurrence of cyanobacteria and their toxins in water bodies used for the production of drinking water poses a technical challenge for water utility managers. With respect to their removal in water treatment procedures, of the more than 60 microcystin congeners, microcystin-LR (L, L-leucine; R, L-arginine) is the best studied cyanobacterial toxin, whereas information for the other toxins is largely lacking. In response to the growing concern about nonlethal acute and chronic effects of microcystins, the World Health Organization has recently set a new provisional guideline value for microcystin-LR of 1.0 pg/L drinking water. This will lead to further efforts by water suppliers to develop effective treatment procedures to remove these toxins. Of the water treatment procedures discussed in this review, chlorination, possibly micro-/ultrafiltration, but especially ozonation are the most effective in destroying cyanobacteria and in removing microcystins. However, these treatments may not be sufficient during bloom situations or when a high organic load is present, and toxin levels should therefore be monitored during the water treatment process. In order to perform an adequate human risk assessment of microcystin exposure via drinking water, the issue of water treatment byproducts will have to be addressed in the future.

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Distribution of tritiated dihydromicrocystin in swine

Cited by 22 publications

References 26 publications

Guidance values for microcystins in water and cyanobacterial supplement products (blue-green algal supplements): a reasonable or misguided approach?

Guidance values for microcystins in water and cyanobacterial supplement products (blue-green algal supplements): a reasonable or misguided approach?

Toxin mixture in cyanobacterial blooms – a critical comparison of reality with current procedures employed in human health risk assessment

Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment.

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