Erratum: Retraction of the landmark glyphosate safety publication by Williams, Kroes and Munro (2000) should be reversed.
[This corrects the article on p. 1107 in vol. 25, PMID: 42517087.].
Published Erratum↗
Biomedical subjects
Daniel R Dietrich
Publications and source records attributed to Daniel R Dietrich.
Retraction of the landmark glyphosate safety publication by Williams, Kroes and Munro (2000) should be reversed.
The decision by the co-Editor-in-Chief of Regulatory Toxicology and Pharmacology, Prof. Martin van den Berg, to retract the 2000 review article by Williams, Kroes, and Munro has elicited widespread criticism within the scientific community. Issued in late 2025, the retraction decision cites procedural concerns including potential ghostwriting, undisclosed conflicts of interest, and omission of certain unpublished studies, invoking Committee on Publication Ethics guidelines despite lacking evidence of fraud or scientific flaws. This editorial argues that the retraction decision involves editorial overreach and misapplication of the guidelines. The alleged omissions stemmed from proprietary data access limitations that were disclosed in the original paper. Subsequent reviews by several independent expert panels and regulatory authorities with access to all glyphosate data, including the studies cited by the retracting editor, reached similar conclusions. Claims of ghostwriting were previously investigated and found lacking, including a declaration by EFSA as to the clarity of the conflict disclosures. The retraction's timing, reliance on litigation documents, and apparent biases that were not disclosed in the retraction notice raise questions of ideological interference. Absent substantive rebuttals based on scientific merit rather than speculative claims of inappropriate authorship and data access, this retraction decision sets a dangerous precedent for retroactive censorship, potentially chilling beneficial industry-academic collaborations and eroding trust in the integrity of scientific publishing. With the strongest conviction, we assert that retracting a paper without scientific flaws isn't protection-it is censorship. We therefore call for the immediate reversal of this flawed and unjustified retraction to preserve trust in peer-reviewed literature.
COPE↗
Production and characterization of monoclonal antibodies against ochratoxin B.
Monoclonal antibodies against ochratoxin B (OTB) were generated by immunizing Balb/c mice with OTB conjugated to keyhole limpet hemocyanin (KLH) via carbodiimide reactions with CHMC and EDAC. A stable hybridoma cell line 2F1.E10 was produced by fusion of murine splenocytes and myeloma cells. The obtained antibodies were characterized using an indirect competitive ELISA. The detection limit was calculated (27+/-2 nM OTB) and 50% binding inhibition was reached at 500 nM free OTB. A low cross-reactivity to ochratoxin A (OTA) of 3.3% and no cross-reactivities to either coumarin or DL-phenylalanine were observed, suggesting a highly specific OTB antibody. The antibody type was identified as IgG class 1 with the light chain being of the kappa configuration. These antibodies can be used in an indirect competitive ELISA to detect OTB in the nanomolar to micromolar concentration range and may be useful for the analysis of contaminated food items.
Animals↗
Establishment of a protocol for the gene expression analysis of laser microdissected rat kidney samples with affymetrix genechips.
Laser microdissection in conjunction with microarray technology allows selective isolation and analysis of specific cell populations, e.g., preneoplastic renal lesions. To date, only limited information is available on sample preparation and preservation techniques that result in both optimal histomorphological preservation of sections and high-quality RNA for microarray analysis. Furthermore, amplification of minute amounts of RNA from microdissected renal samples allowing analysis with genechips has only scantily been addressed to date. The objective of this study was therefore to establish a reliable and reproducible protocol for laser microdissection in conjunction with microarray technology using kidney tissue from Eker rats p.o. treated for 7 days and 6 months with 10 and 1mg Aristolochic acid/kg bw, respectively. Kidney tissues were preserved in RNAlater or snap frozen. Cryosections were cut and stained with either H&E or cresyl violet for subsequent morphological and RNA quality assessment and laser microdissection. RNA quality was comparable in snap frozen and RNAlater-preserved samples, however, the histomorphological preservation of renal sections was much better following cryopreservation. Moreover, the different staining techniques in combination with sample processing time at room temperature can have an influence on RNA quality. Different RNA amplification protocols were shown to have an impact on gene expression profiles as demonstrated with Affymetrix Rat Genome 230_2.0 arrays. Considering all the parameters analyzed in this study, a protocol for RNA isolation from laser microdissected samples with subsequent Affymetrix chip hybridization was established that was also successfully applied to preneoplastic lesions laser microdissected from Aristolochic acid-treated rats.
Animals↗
Oral toxicity of the microcystin-containing cyanobacterium Planktothrix rubescens in European whitefish (Coregonus lavaretus).
The microcystin-producing cyanobacterium Planktothrix is one of the most widespread genera amongst toxin producing cyanobacteria in European lakes. In particular, the metalimnic blooms of Planktothrix rubescens have been associated with growing problems in the professional freshwater fishery as a decrease in yearly yields in the important coregonids fishery often coincides with the appearance of P. rubescens. P. rubescens is a cyanobacterial species known to produce toxic compounds, e.g. microcystins. Although microcystins have been reported to affect fish health, behaviour, development and growth and have also been associated with feral fish kills, there is currently no specific information on the effects of toxic Planktothrix filaments in fish and especially coregonids. Therefore, the aim of this study was to investigate the effects of an environmentally relevant dose of P. rubescens filaments orally applied to coregonids and to discuss the findings in the context of microcystin toxicity previously reported in carp and trout. A single dose of P. rubescens culture, at a density of 80,000 cells per 120 microl, was applied to coregonids thus corresponding to 0.6-0.9 microg microcystin-LR(equiv.)/kg body weight. Behavioural changes and opercular beat rates, growth, hepatosomatic index, condition and plasma glucose were determined. Liver, kidney, gill and the gastrointestinal tract were assessed histopathologically and immunohistologically. Exposed fish showed behavioural changes, increased opercular beat rates and elevated plasma glucose levels, possibly representing a physiological stress response. Histopathological alterations in liver, gastrointestinal tract and kidney, also immunopositive for microcystin suggested causality of tissue damage and the in situ presence of microcystins. The observed combination of stress and organ damage may explain the frequently reduced weight and thus the fitness noted in coregonids subjected to regular occurrences of stratified and dispersed P. rubescens blooms, e.g. in lake Ammersee, Bavaria, Germany.
Administration, Oral↗
Effects of BPA in snails.
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Analysis of Variance↗
Stimulation of reproductive growth in rainbow trout (Oncorhynchus mykiss) following exposure to treated sewage effluent.
Rainbow trout (Oncorhynchus mykiss) were exposed to 1.5 and 15% v/v secondary treated sewage effluent for 32 weeks in flow-through mesocosms. The exposure encompassed the full period of reproductive development for rainbow trout. Trout did not show any evidence of a dose-dependent change in growth. Fish exposed to 15% effluent were the only group to show mortality (5%) over the duration of the experiment. Trout at the highest effluent concentration had significantly higher liver size than reference water fish. Both male and female trout in the 15% exposure group also exhibited significantly higher gonad weight than the reference group. In female trout, this gonad size increase could be explained by higher egg numbers. Female and male trout both displayed a significant increase in plasma 17 beta-estradiol levels after exposure to 15% effluent, while neither sex had dose-dependent differences in plasma testosterone. Male trout displayed elevated vitellogenin levels and reduced plasma 11-ketotestosterone concentration after exposure to 15% effluent. Chemical examination of steroidal compounds, including both estrogens and androgens, in the wastewater revealed that only estrone was detectable at a mean concentration of 4.5 ng/L. It is assumed that the effects observed in trout exposed to 15% effluent were consistent with stimulation of reproductive development due to very low levels of estrogens. Overall, long-term exposure to treated sewage effluent containing low levels of estrogen did not have significant negative implications for reproductive development in rainbow trout.
Animals↗
Characterization of microcystin production in an Antarctic cyanobacterial mat community.
Cyanobacteria are well known for their production of non-ribosomal cyclic peptide toxins, including microcystin, in temperate and tropical regions, however, the production of these compounds in extremely cold environments is still largely unexplored. Therefore, we investigated the production of protein phosphatase inhibiting microcystins by Antarctic cyanobacteria. We have identified microcystin-LR and for the first time [D-Asp3] microcystin-LR by mass spectrometric analysis in Antarctic cyanobacteria. The microcystins were extracted from a benthic microbial community that was sampled from a meltwater pond (Fresh Pond, McMurdo Ice Shelf, Antarctica). The extracted cyanobacterial cyclic peptides were equivalent to 11.4 ng MC-LR per mg dry weight by semi-quantitative analyses using HPLC-DAD and the protein phosphatase inhibition assay. Furthermore, we were able to identify the presence of cyanobacterial non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes in total DNA extracts from the mat community.
Animals↗
Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario).
The detection of residues of various pharmaceuticals in surface waters during the last two decades has prompted concerns about possible adverse effects of this kind of pollution on aquatic organisms. The objective of the present study was to investigate effects of the non-steroidal anti-inflammatory drug diclofenac, one of the pharmaceuticals most prevalent in surface waters, on brown trout (Salmo trutta f. fario), a salmonid species native to German rivers. Brown trout were exposed to 0.5, 5 and 50 microg/L diclofenac for 7, 14 and 21 days, whereby the lowest exposure concentration is comparable with concentrations commonly found in the aquatic environment. Fish exposed to diclofenac displayed significantly reduced haematocrit levels after 7 and 14 days of exposure. After 21 days, trout were examined for histopathological alterations, whereby diclofenac exposure resulted in increased monocyte infiltration in the liver, telangiectasis in gills, and the occurrence of interstitial hyaline droplets, interstitial proteinaceous fluid and mild tubular necrosis in trunk kidney. Concurrent immunohistological analysis revealed an increase of granulocyte numbers in primary gill filaments, as well as granulocyte accumulation and increased major histocompatibility complex (MHC) II expression in kidney, suggestive of an inflammatory process in these organs. Moreover, the ability of diclofenac to hinder the stimulation of prostaglandin E2 synthesis was shown in head kidney macrophages of brown trout in vitro. These findings support the hypothesis that environmental exposure of fish to diclofenac provokes the same mechanism of action in these non-target organisms as previously described for mammalian species and can thus lead to similar (possibly adverse) effects. In general, the present study suggests that exposure of brown trout to diclofenac in concentration ranges commonly found in the environment can result in adverse effects in various organs and possibly compromise the health of affected fish populations.
Animals↗
Science and politics: from science to decision making.
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Decision Making↗
Sex and low-level sampling stress modify the impacts of sewage effluent on the rainbow trout (Oncorhynchus mykiss) immune system.
The objective of the present study was to investigate the influence of chronic exposure to municipal sewage treatment effluent at environmentally relevant concentrations on immune parameters in rainbow trout (Oncorhynchus mykiss), including the assessment of potential differences in reactivity between sexually mature male and female fish. Trout were exposed to 1.5 and 15% (v/v) secondary treated municipal sewage effluent for 32 weeks. Fish were injected intra-peritoneally either with inactivated Aeromonas salmonicida to simulate an infection or with PBS as control for this immune challenge 6 weeks prior to sampling. Exposure to effluent resulted in a decrease in A. salmonicida-specific serum antibody level and blood lymphocyte numbers in mature females, but not in male fish. Injection of A. salmonicida resulted in enhanced serum lysozyme activity in mature male trout, which were not exposed to effluent. This stimulating effect of A. salmonicida could not be found in effluent-exposed trout, again potentially revealing a suppressive effect of the effluent. An influence of sampling fish on two consecutive days was observed in many immune parameters, most likely reflecting handling stress. Leucocyte and lymphocyte numbers in peripheral blood were consistently lower in male and female fish on the second sampling day. Phagocytosis in head kidney macrophages from male trout was also influenced by sampling day, whereby a stimulation of this reaction occurred on the second day of sampling. Liver mixed function oxygenase activity was found to be enhanced in mature male trout exposed to 15% effluent. In conclusion, the study showed, that exposure to sewage treatment plant effluent, in surface water relevant concentrations, can lead to potentially adverse effects on selected immune reactions in rainbow trout. However, this study also demonstrated that both handling stress and the sex of mature fish have distinct influences on the immune response detected in male and female fish and are likely to influence measured immune parameters to the extent that subtle effluent induced changes may be difficult to detect.
Aeromonas salmonicida↗
Occurrence and elimination of cyanobacterial toxins in drinking water treatment plants.
Toxin-producing cyanobacteria (blue-green algae) are abundant in surface waters used as drinking water resources. The toxicity of one group of these toxins, the microcystins, and their presence in surface waters used for drinking water production has prompted the World Health Organization (WHO) to publish a provisional guideline value of 1.0 mug microcystin (MC)-LR/l drinking water. To verify the efficiency of two different water treatment systems with respect to reduction of cyanobacterial toxins, the concentrations of MC in water samples from surface waters and their associated water treatment plants in Switzerland and Germany were investigated. Toxin concentrations in samples from drinking water treatment plants ranged from below 1.0 microg MC-LR equiv./l to more than 8.0 microg/l in raw water and were distinctly below 1.0 microg/l after treatment. In addition, data to the worldwide occurrence of cyanobacteria in raw and final water of water works and the corresponding guidelines for cyanobacterial toxins in drinking water worldwide are summarized.
Bacterial Toxins↗
Investigation of the teratogenic potential of ochratoxin A and B using the FETAX system.
BACKGROUND: Ochratoxin A (OTA) is a mycotoxin produced by certain Aspergillus and Penicillium species. It has been observed to be teratogenic in a number of animal models including rat, mouse, hamster, and chick, with reduced birth weight and craniofacial abnormalities being the most commonly observed malformations. Neither the potential of OTA to cause malformations in humans nor its teratogenic mode of action is known. The FETAX system is an embryotoxicity assay system, with a high correlation to animal models and epidemiological data. Analysis of OTA-mediated teratogenesis using this system could provide a useful tool for the generation of high numbers of samples for mechanistic studies. METHODS: Using the standard ASTM 96-hr exposure protocol, the effect of OTA and its structural analogue OTB on the development of Xenopus laevis embryos in vitro was assessed. The accumulation of both substances in Xenopus embryos was also examined using tritiated OTA and OTB. RESULTS: Both OTA and OTB caused craniofacial malformations, while OTA also caused reduced embryo growth. As expected, OTA was far more potent in inducing these effects than OTB. This could at least in part be due to greater levels of OTA being accumulated within the embryos. CONCLUSIONS: The ability of FETAX to differentiate between close structural analogues indicates the assay has great potential for the elucidation of the embryotoxic and teratogenic mechanisms of action. Hence, the model could provide a suitable system for the investigation of other known teratogens or for the pre-screening of new agents for teratogenic potential.
Abnormalities, Drug-Induced↗
Recovery of MC-LR in fish liver tissue.
Cyanotoxins, particularly microcystins (MCs), have been shown to be a hazard to human health. MCs accumulate in aquatic organisms probably as a result of irreversible binding to liver protein phosphatases. The aim of this study was to describe the recovery of MC from fish liver using various detection methods, with MC-LR as the representative congener. These findings are discussed in conjunction with the current procedures and limit values used for human risk assessment. Following incubation of liver homogenates with various MC-LR concentrations, the homogenates were extracted by a water/methanol/butanol mixture via different treatments and subsequently analyzed via the colorimetric protein phosphatase inhibition assay (cPPA), HPLC, and anti-Adda ELISA. Detection via cPPA appeared to yield the highest recovery of MC-LR, although the presence of unspecific background may have resulted in overestimation of the true recovery. The recoveries determined via HPLC and anti-Adda ELISA were comparable to each other. The limits of detection were 0.01-2.4 microg MC-LR/g liver tissue, depending on the method used. Maximum MC-LR recovery from samples incubated with 10 and 100 microg MC-LR/g ranged between 44% and 101%. Recovery from samples incubated with 1 microg MC-LR/g liver tissue was below 3%. Lower recovery is assumed to result from irreversible, covalent MC protein binding, as confirmed by Western blotting of liver homogenates with anti-Adda immunoprobing. The results demonstrate that further investigation of and improvement in routinely applied MC methods for fish tissue and/or food analyses are needed for a reliable risk assessment.
Animals↗
Ochratoxin A: comparative pharmacokinetics and toxicological implications (experimental and domestic animals and humans).
The causal factors for the species- and sex-differences associated with ochratoxin-mediated toxicity remain unclear. Variations in kinetic parameters may play a major role in explaining these differences, however, discrepancies and inaccuracies in the toxicokinetics reported in the literature for various species, make comparison and hence the extrapolation to the human situation impossible. The one- and two-compartment open models currently proposed may be insufficient to enable an accurate representation of the actual situation in vivo. It is likely that at least three if not four compartments must be assumed to account for the reported effects. The application of such models to existing raw data would most likely provide for a more accurate base set of toxicokinetic data and contribute to a more accurate human risk assessment. Possible explanations for the reported inconsistencies and their impact on the proposed mechanism(s) of action of OTA and risk assessment are discussed.
Animals↗
Ochratoxin A: the continuing enigma.
The mycotoxin ochratoxin A (OTA) has been linked to the genesis of several disease states in both animals and humans. It has been described as nephrotoxic, carcinogenic, teratogenic, immunotoxic, and hepatotoxic in laboratory and domestic animals, as well as being thought to be the probable causal agent in the development of nephropathies (Balkan Endemic Nephropathy, BEN and Chronic Interstitial Nephropathy, CIN) and urothelial tumors in humans. As a result, several international agencies are currently attempting to define safe legal limits for OTA concentration in foodstuffs (e.g., grain, meat, wine, and coffee), in processed foods, and in animal fodder. In order to achieve this goal, an accurate risk assessment of OTA toxicity including mechanistic and epidemiological studies must be carried out. Ochratoxin has been suggested by various researchers to mediate its toxic effects via induction of apoptosis, disruption of mitochondrial respiration and/or the cytoskeleton, or, indeed, via the generation of DNA adducts. Thus, it is still unclear if the predominant mechanism is of a genotoxic or an epigenetic nature. One aspect that is clear, however, is that the toxicity of OTA is subject to and characterized by large species- and sex-specific differences, as well as an apparently strict structure-activity relationship. These considerations could be crucial in the investigation of OTA-mediated toxicity. Furthermore, the use of appropriate in vivo and in vitro model systems appears to be vital in the generation of relevant experimental data. The intention of this review is to collate and discuss the currently available data on OTA-mediated toxicity with particular focus on their relevance for the in vivo situation, and also to suggest possible future strategies for unlocking the secrets of ochratoxin A.
Animals↗
Diversity within cyanobacterial mat communities in variable salinity meltwater ponds of McMurdo Ice Shelf, Antarctica.
This study investigated the diversity of cyanobacterial mat communities of three meltwater ponds--Fresh, Orange and Salt Ponds, south of Bratina Island, McMurdo Ice Shelf, Antarctica. A combined morphological and genetic approach using clone libraries was used to investigate the influence of salinity on cyanobacterial diversity within these ecosystems without prior cultivation or isolation of cyanobacteria. We were able to identify 22 phylotypes belonging to Phormidium sp., Oscillatoria sp. and Lyngbya sp. In addition, we identified Antarctic Nostoc sp., Nodularia sp. and Anabaena sp. from the clone libraries. Fresh (17 phylotypes) and Orange (nine phylotypes) Ponds showed a similar diversity in contrast to that of the hypersaline Salt Pond (five phylotypes), where the diversity within cyanobacterial mats was reduced. Using the comparison of identified phylotypes with existing Antarctic sequence data, it was possible to gain further insight into the different levels of distribution of phylotypes identified in the investigated cyanobacterial mat communities of McMurdo Ice Shelf.
Antarctic Regions↗
Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss).
In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune parameters due to effluent exposure were caused by the direct action of chemicals, or were due to a general stress response.
Aeromonas salmonicida↗