Comments on “Ochratoxin A: In utero Exposure in Mice Induces Adducts in Testicular DNA. Toxins 2010, 2, 1428–1444”—Mis-Citation of Rat Literature to Justify a Hypothetical Role for Ochratoxin A in Testicular Cancer

A manuscript in the journal recently cited experimental rat data from two manuscripts to support plausibility of a thesis that ochratoxin A might be a cause of human testicular cancer. I believe that there is no experimental evidence that ochratoxin A produces testicular cancer in rats or mice

An investigation into the behaviour and performance of a recirculating system for intensive fish culture

The role of fish culture in the provision of fish for food is examined with special reference to Western Europe. The use of recirculating systems for intensive fish culture is considered and the need for establishing their feasibility for commercial culture recognised. The lack of suitable guidelines for the design and operation of such systems is seen as a major limitation. A research programme was initiated, resulting in the development of a simulation model. Firstly a number of recirculating systems were designed,constructed and commissioned and their behaviour and performance monitored. Three areas for further investigation were noted and experiments to consider growth and food conversion, the production and accumulation of wastes and filter performance were conducted. Based on the understanding gained a simulation model was constructed. The model was verified using graph theory, by inspection of standard runs for maximum, minimum, mean and variation and by sensitivity analysis. The model was validated by the comparison of model output with the actual behaviour of the system using a range of stocking densities and ration levels. To improve agreement between predicted and measured diurnal variations in water quality, modifications to the simulation of ammonia production and short-circuiting in the filter were considered. The use of the model is considered; to indicate areas of inadequate knowledge, to improve understanding of the behaviour of the laboratory systems and to develop guidelines for determining carrying capacity and optimum design of filters for recirculating systems. Use of the model for predictive purposes posed a number of difficulties, and it is concluded that the main value of the model is as an educational tool

Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat

Binding of Ochratoxin A to a Urinary Globulin: A New Concept to Account for Gender Difference in Rat Nephrocarcinogenic Responses

SDS-gradient mini-gel electrophoresis and immunoblotting of urine of rats given ochratoxin A (OTA), showed OTA binding to an α2u-globulin. Perceived potential internalised delivery of OTA to proximal tubule epithelia by the carrier, specific only to adult male rats and augmenting other uptake mechanisms, suggests that some experimental nephrotoxicological data may not be appropriate for human risk assessment. Reexamination of female rat renal tumour histopathology of the NTP high dose OTA study showed all carcinomas were solitary, unilateral, microscopic and clinically insignificant at the 2-year end-stage. The novel concept, when consolidated further from our archived material, may moderate current perceptions of the human risk of traces of dietary OTA

Oncological Outcomes in Rats Given Nephrocarcinogenic Exposure to Dietary Ochratoxin A, Followed by the Tumour Promoter Sodium Barbital for Life: A Pilot Study

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours

1H NMR Spectroscopy-Based Metabolomic Assessment of Uremic Toxicity, with Toxicological Outcomes, in Male Rats Following an Acute, Mid-Life Insult from Ochratoxin A

Overt response to a single 6.25 mg dose of ochratoxin A (OTA) by oral gavage to 15 months male rats was progressive loss of weight during the following four days. Lost weight was restored within one month and animals had a normal life-span without OTA-related terminal disease. Decline in plasma OTA concentration only commenced four days after dosing, while urinary excretion of OTA and ochratoxin alpha was ongoing. During a temporary period of acute polyuria, a linear relationship between urine output and creatinine concentration persisted. Elimination of other common urinary solutes relative to creatinine was generally maintained during the polyuria phase, except that phosphate excretion increased temporarily. 1H NMR metabolomic analysis of urine revealed a progressive cyclic shift in the group principal components data cluster from before dosing, throughout the acute insult phase, and returning almost completely to normality when tested six months later. Renal insult by OTA was detected by 1H NMR within a day of dosing, as the most sensitive early indicator. Notable biomarkers were trimethylamine N-oxide and an aromatic urinary profile dominated by phenylacetylglycine. Tolerance of such a large acute insult by OTA, assessed by rat natural lifetime outcomes, adds a new dimension to toxicology of this xenobiotic

Pearl Millet as an Alternate Host of the Sorghum Ergot Pathogen, Claviceps africana

The infectivity of C. africana on pearl millet (Pennisetum glaucum) lines in Africa was studied. C. africana consistently gave 100% disease incidence on male-sterile sorghum in experiments undertaken in Zimbabwe. C. fusiformis established disease with moderate incidence on most but not all lines tested. In contrast, C. africana established a parasitic association with all the pearl millet lines tested, with incidence as high as 23% in ICMSR 260, the genotype that also supported the highest incidence with C. fusiformis. However, the disease severities were always low, between 1 and 5%. All infections on pearl millet were verified as the sphacelial stage by virtue of their conidial characteristics. After 1 passage through a pearl millet host, C. africana did not apparently become more infectious on this host

Assessment of workpiece surface integrity and dimensional/geometrical accuracy following finish plunge end milling of holes drilled with worn tools in PM-processed nickel based superalloy

Powder metallurgy (PM) processed nickel-based superalloys are increasingly employed in the hot section of gas turbine engines for parts such as high-pressure (HP) compressors and turbine rotor discs over more traditional cast and wrought options such as Inconel 718 due to its improved high-temperature properties. In this paper, the surface integrity and geometrical/dimensional accuracy of holes initially rough drilled using worn tools and subsequently finish plunge end milled in a proprietary PM-processed Ni-based superalloy, were assessed and compared. The influence of tool wear on hole quality after finish plunge end milling was also investigated. Significant improvement in hole quality was evident following finishing with reductions in surface roughness (up to ~86%), subsurface microhardness (up to ~125 HK0.05) and workpiece microstructure deformation/damage (up to ~80% in terms of average depth) compared to corresponding rough drilled holes. Evidence of chatter marks on holes machined with worn plunge end mills was observed, despite exhibiting reduced surface roughness levels (~45-73%). Generally, somewhat improved hole surface integrity (reduced subsurface deformation by ~47-64%) and geometrical accuracy (circularity decreased by ~10-25%) were produced when employing new tools.</p