Timely awareness and prevention of emerging chemical and biochemical risks in foods: Proposal for a strategy based on experience with recent cases

A number of recent food safety incidents have involved chemical substances, while various activities aim at the early identification of emerging chemical risks. This review considers recent cases of chemical and biochemical risks, as a basis for recommendations for awareness and prevention of similar risks at an early stage. These cases include examples of unapproved genetically modified food crops, intoxications with botanical products containing unintentionally admixed toxic herbs, residues of unapproved antibiotics and contaminants in farmed aquaculture species such as shrimp and salmon; and adverse effects of chemical and biological pesticides of natural origin. Besides case-specific recommendations for mitigation of future incidents of the same nature, general inferences and recommendations are made. It is recommended, for example, to establish databases for contaminants potentially present within products. Pro-active reconnaissance can facilitate the identification of products potentially contaminated with hazardous substances. In international trade, prevention and early identification of hazards are aided by management systems for product quality and safety, rigorous legislation, and inspections of consignments destined for export. Cooperation with the private sector and foreign authorities may be required to achieve these goals. While food and feed safety are viewed from the European perspective, the outcomes also apply to other regions.     

雷州半岛农村臭鼩鼱生物学观察

目的 了解雷州半岛农村臭鼩鼱的生态情况。方法 夹日法进行密度调查,同时结合鼠蚤监测所捕获的臭鼩鼱调查其种群构成及繁殖情况。结果 臭鼩鼱年均室内、野外密度分别为2．37％、0．61％．年均室内、野外种群构成分别为29、50％、11．54％,年均妊娠率为43．17％。结论 臭鼩鼱密度和种群构成受环境、气候和药物影响而改变,繁殖率也与气候、密度密切相关。     

四种杀虫剂对雷州半岛灭蚤地区印鼠客蚤的毒性观察

目的观察四种杀虫剂（奋斗呐、氯菊酯、敌敌畏、马拉硫磷）对灭蚤地区印鼠客蚤的毒性。方法将用丙酮配制的药液100μl加在φ35mm的滤纸药膜上,20min后放入50ml离心管盖中,接15匹成蚤于离心管（底部有20个φ0．5mm小孔以通气）中,旋紧盖子并倒置。在温度（25±1）℃,相对湿度（85±5）％的培养箱中接触药膜24h,检查死虫数,计算LC50及95％可信区间范围。结果雷州平步、遂溪洋青、廉江营仔和潮洲饶平（对照点）的印鼠客蚤对奋斗呐、氯菊酯、敌敌畏、马拉硫磷相应的LC50分别为510．51mg／L、923．63mg／L、10．40mg／L、1224．62mg／L;293．22mg／L、349．95mg／L、9．11mg／L、775．00mg／L;255．27mg／L、219．99mg／L、8．27mg／L、559．37mg／L;176．81mg／L、199．66mg／L、5．73mg／L、583．31mg／L。雷州平步、遂溪洋青、廉江营仔各自相应的LC50与潮洲饶平（对照点）的LC50的比值分别为2．89、4．63、1．82、2．10;1．66、1．75、1．59、1．33;1．44、1．10、1．44、0．96。结论除了廉江营仔印鼠客蚤对马拉硫磷毒性敏感外,4种杀虫剂对雷州半岛灭蚤地区的印鼠客蚤的毒性降低,并以雷州平步的情况较为明显。     

Genetic polymorphisms of cytochrome P450 among patients with Balkan endemic nephropathy (BEN)

OBJECTIVES: The concept of multifactorial etiology of BEN anticipates that a combination of polymorphic gene variants and various environmental factors causes an increased risk for the disease. CYP enzymes play a key role in the metabolic activation of environmental chemicals and toxins. CYP3A enzymes are particularly relevant for xenobiotic metabolism because of their broad substrate specificity and abundant expression in the human liver, intestine, and kidney. Previous phenotyping analysis on CYP2D6 enzyme activity in BEN patients proposed a modifying effect of CYP2D6 gene variants on BEN risk, but it was not approved with molecular-genetic methods. The aim of the current case-control study was to compare the frequency of CYP2D6 and CYP3A5 polymorphisms, as well as one CYP3A4 promoter variant in BEN patients and controls in order to investigate a possible association between individual genetic variations in these genes and susceptibility to BEN. DESIGN AND METHODS: Ninety-six nonrelated Bulgarian BEN patients from endemic villages in the Vratza district and 112 healthy Bulgarians from nonendemic areas (controls) were genotyped. Identification of alleles was done by allele-specific PCR or by rapid-cycle amplification on the LightCycler, followed by sequence-specific detection. RESULTS: The UM, PM, and EM + IM genotype frequencies of CYP2D6 did not differ significantly between the two groups (P > 0.05). The CYP3A4*1B allele was only found in the heterozygous form, with allelic frequencies of 5.21% in the patients and 2.23% in the healthy individuals (P = 0.11). The CYP3A5*1 allele was more prevalent in BEN patients with a frequency of 9.38% compared to 5.36% in the controls and was associated with a higher risk for BEN (OR 2.41, 95% CI 1.09-5.33) (P = 0.02). CONCLUSIONS: Our results demonstrate that the CYP3A5*1 allele, previously reported as a marker for CYP3A5 expression in human kidney, is associated with increased risk for BEN, while CYP3A4*1B and CYP2D6 genotypes do not significantly modify the risk for the disease.     

Die freien Aminosäuren im Blutserum bei der Endemischen (Balkan) Nephropathie

Zusammenfassung Bei 6 Kranken mit Endemischer (Balkan) Nephropathie in verschiedenen Stadien der Nierenschädigung wurden mit dem Aminosäuren-Autoanalyzer der Fa. Technicon (Frankfurt a. M.) die freien Aminosäuren im Blutserum untersucht.Es wurde eine ausgeprägte Hyperprolinämie und Hyperalaninämie festgestellt. Bei 2 der untersuchten Patienten wurde durch zweidimensionale Dünnschichtchromatographie des Harns Prolin und Hydroxyprolin nachgewiesen. Bei allen untersuchten Kranken war die Ornithin- und Argininkonzentration im Serum mäßig erhöht, Methionin und Asparaginsäure waren bei 4 der 6 untersuchten Patienten schwach erhöht.Eine Beziehung zwischen der Aminosäurekonzentration im Serum und dem Grad der Stickstoffretention scheint nur für Alanin und Methionin zu bestehen. Die Serumwerte sind aber auch bei den Patienten ohne Stickstoffretention und erfaßbare Niereninsuffizienz erhöht. Es handelt sich um ein spezielles Hyperaminoacidämie-Muster. Die gefundenen Veränderungen im Serum-Aminosäuremuster besitzen wahrscheinlich keinen Zusammenhang mit der Nierenkrankheit.Das häufige familiäre Auftreten der Endemischen Nephropathie läßt auf eine vorhandene schwache Stelle im intermediären Metabolismus vermuten, möglicherweise verbunden mit genetischen Faktoren, die sich unter bestimmten Bedingungen manifestieren. Man könnte annehmen, daß es sich um eine Stoffwechselstörung handelt, die durch denselben nephrotoxischen Faktor, welcher das Nierenleiden und die sehr oft bei ihm vorhandenen Leberschädigung und Neoplasie der Nieren und der Harnwege verursacht, bedingt ist.Ständige Adresse: Forschungsgruppe für Herz- und Gefäßkrankheiten bei der Abteilung für Medizinische Wissenschaften der Bulgarischen Akademie der Wissenschaften (Direktor: Prof. Dr. A. Puchlev), Sofia. Bulgarien.     

Balkan Endemic Nephropathy is Still Present in the Kolubara Region,Serbia

Background. Almost 50 years ago Balkan Endemic Nephropathy (BEN) was first described in Serbia in the village of ?opi? where the first field examination was carried out in 1971. Our aim was to find out whether BEN is still present in this region. Methods. Prevalence data on BEN from a field examination run in 1971 were compared with the results of a cross-sectional study conducted in the same village in 1992. In addition, every new case of the disease diagnosed between 1971 and 1992 was recorded retrospectively. The prospective study included 50 members of five BEN families randomly selected from 28 BEN families registered in the village ?opi? in 1992. The objective survey and examination of global and tubular kidney function was carried out in all examined persons once yearly in 1998, 1999, and 2000. Results. The overall prevalence of BEN was 6.4% in 1971 and 8.9% in 1992. In the period of 21 years, 161 new BEN patients were detected in 28 families in which the disease had already been recorded. No new family affected by BEN and none of the new patients in 47 families registered previously as nonaffected were discovered. In the prospective study of five BEN families, three new BEN cases were discovered among 50 members, and two patients fulfilled criteria for BEN-suspected ones. Conclusion. Balkan Endemic Nephropathy (BEN) is still present in the village of ?opi?, but the clinical course of the disease became more protracted over time. New cases of BEN appeared only in the affected families.     

High Incidence of Benign Brain Meningiomas among Iranianborn Jews in Israel may be Linked to both Hereditary and Environmental Factors

Background: Following research demonstrating an increased risk for meningiomas in the Jewish populationof Shiraz (Iran) we conducted a cohort analysis of meningiomas among Jews originating in Iran and residingin Israel. Materials and Methods: We use the population-based registry data of the Israeli National CancerRegistry (INCR) for the main analysis. All benign meningioma cases diagnosed in Israel from January 2000 tothe end of 2009 were included. Patients that were born in Iran, Iraq, Turkey, Bulgaria and Greece were usedfor the analysis, whereby we calculated adjusted incidence rates per 100,000 people and computed standardizedincidence ratios (SIRs) comparing the Iranian-born to each of the three other groups. Results: Iranian-bornJews had statistically significant higher meningioma rates rates compared to other Jews originating in Balkanstates: 1.46 fold compared to Turkish Jews and 1.86 fold compared to the Bulgaria-Greece group. There was asmall increase in risk for the Iranian born group compared to those who were born in Iraq (1.06, not significant).Conclusions: Higher rates of meningiomas were seen in Jews originating in Iran that are living in Israel ascompared to rates in neighboring countries of origin. These differences can be in part attributed to early lifeenvironmental exposures in Iran but probably in larger amount are due to genetic and hereditary factors in aclosed community like the Iranian Jews. Some support for this conclusion was also found in other publishedresearch.     

Kinetics of aristolochic acid I after oral administration of Radix Aristolochiae or Guanxinsuhe preparation in canines

Ethnopharmacological relevance

Aristolochic acid I (AAI), a major component derived from Aristolochia species, which have been known for a long time and remain in use today, particularly in Asia and Central America. It has been confirmed to induce a type of so-called aristolochic acid nephropathy (AAN) and involved in the development of Balkan endemic nephropathy (BEN).

Aim of the study

To investigate the kinetic of AAI in beagle dogs after single-dose oral administration of Radix Aristolochiae or its preparation, Guanxinsuhe, as well as the effects of compound compatibility in traditional Chinese medicine on the pathologic processes of AAN.

Materials and methods

Beagle dogs were orally administrated Radix Aristolochiae (0.3 g/kg/day), Guanxinsuhe preparation (0.9 g/kg/day) (with an identical dosage of AAI), and empty capsules respectively for 180 days. Canines (n=2) were euthanized on day 90, 180, 210, HPLC was established to determine the AAI level in plasma and the kinetic behaviors of AAI in dogs were elucidated after single dosing. Hematoxylin and eosin (H&E)-staining was applied for histopathologic examination to evaluate the pathological status of kidneys.

Results

Compared to canines with Radix Aristolochiae treatment, the Cmax, AUC, Tmax, and t_1/2β of AAI in Guanxinsuhe preparation group were elevated, while t_1/2α of AAI was decreased. The results indicated the co-existing components in Guanxinsuhe preparation could increase the absorption, accelerate the distribution, but delay the absorption and elimination of AAI. After long-term dosing, animals treated with Radix Aristolochiae were found with more severe renal impairment and higher AAI level in plasma.

Conclusions

It was demonstrated that the compound compatibility in Guanxinsuhe preparation can affect the kinetic process of AAI and attenuate the toxic effect on kidney when the duration of treatment was prolonged.     

Upper urothelial carcinoma in Balkan endemic nephropathy and non-endemic regions: A comparative study of pathological features

Upper urothelial carcinoma (UUC), a rare neoplasm, occurs more frequently in some regions of Balkan countries than in other areas in the world. The aim of this study is to compare phenotypic morphological characteristics of UUC in Balkan endemic nephropathy (BEN) region and control rural and city populations free of BEN, and to determine the characteristic(s) that could discriminate tumors in endemic and non-endemic regions. The authors analyzed biopsies from 88 patients with UUC, 40 patients who live in Balkan endemic (BEN) settlements and 48 control subjects. The histological sections were used to assess morphological variables: histologic grade, pathologic stage (pT), growth pattern, pattern of invasion, lympho-vascular invasion (LVI), presence of necrosis and metaplastic changes (squamous or glandular) within the tumor. Statistically significant differences between the groups were found concerning tumor grade, pattern of invasion, growth pattern and metaplastic changes. High-grade tumors and trabecular/infiltrative patterns of invasion were more frequent in the group of BEN tumors (χ²=4.583, p<0.05; χ²=8.064, p<0.05). Moreover, solid growth and metaplastic changes are significant in BEN tumor, χ²=9.696, p<0.01; χ²=9.35, p<0.01, respectively. Discriminant analysis of morphological variables had indicated that BEN and control tumors are significantly different (Wilks’ lambda=0.833, χ²=15.044 and p<0.05). The best characteristic that differentiated them was growth pattern; i.e., solid growth for BEN tumors and papillary for control tumors.