Kidney: Toxicological Assessment

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A certain percentage depending on the animal species used of the fetuses are then prepared for visceral examination and the remainder for examination of skeletal anomalies. Although the litter is considered the most relevant unit for statistical analysis, data should also be presented and assessed for each fetus. Historical control data are also useful for determining the biological importance of visceral or skeletal anomalies that are elevated to a statistically significant level by treatment. Again, only historical control data from studies on the same species and strain of animal should be used for comparison purposes.

At least one developmental toxicity formerly teratogenicity study Guideline ; EPA, would now be required for all nonfood uses. In the past it was required only if there was expected exposure of women of childbearing age. A second study could be required if concerns are raised from the results of the first study.

For food use EUPs accompanied by a temporary tolerance request, a second study could also be required, depending on the results of the first study. A postnatal development toxicity study Guideline ; EPA, is proposed as a conditional requirement. This study could be required to more fully assess the manifestations of developmental toxicity, especially potential deficits in function or developmental neurotoxicity.

The parameters that need to be studied in a postnatal study depend on the effects seen in the prenatal study. Guidelines are presently being developed by EPA. Multigeneration reproduction studies are designed to provide information concerning the general effects of a test substance on overall reproductive. Such studies may also provide information about the effects of the test substance on neonatal morbidity and mortality and about the meaning of preliminary data for developmental toxicity. EPA requires that the study include a minimum of two generations and that one litter be produced each generation.

Dosing of both parents should begin when they are 8 weeks old and continue for 8 weeks prior to mating. Dosing of parental males should continue at least until mating is completed. Dosing of parental females continues through a 3-week mating period and pregnancy and up to the time of weaning 3 weeks after delivery of the pups. Dosing of pups selected for mating to produce the second generation should begin at weaning and continue as discussed above. The dosing and breeding schedule is clarified in the timeline presented in Table Parental animals should be observed daily for signs of toxicity.

This is especially important for females during pregnancy in order to detect signs of difficult or prolonged parturition. Weights of parental animals are recorded weekly. The duration of pregnancy should be determined from the time evidence of mating was first observed. Each litter should be examined for the number of dead and live pups and for gross abnormalities. Live pups should be individually weighed on days 0 optional , 4, 7 optional , 14, and 21 after birth.

A complete gross necropsy should be performed on all parental animals, all pups found dead prior to day 21 weaning , and all weanlings not selected as parental animals for a next generation. Pups culled on day 4 do not have to undergo gross necropsy. Histopathology is required for reproductive and target organs those known from previous studies to be adversely affected by the test material for all control and high-dose parental animals and should be conducted on weanling animals except for those selected as parental animals in the next generation as described for parental animals EPA, The addition of a fertility assessment of parental males is recommended by EPA if fertility or reproductive parameters are found to be affected by the test chemical.

The parameters to be examined or reported in this assessment include weight of reproductive organs, spermatid count, total cauda epididymal sperm count, assessment of sperm morphology and motility, examination of epididymal fluid for debris and unexpected cell types, and additional histopathology of the testes. A reproduction study Guideline ; EPA, could also be required to support nonfood uses if adverse effects on the reproductive system or developmental toxicity are observed in other studies.

Dosing of P 1 males may end at week 25; P 1 females are killed. F 1 mating; dosing of F 1 males may end at week 40; F 1 males killed. A battery of mutagenicity tests is required to assess the potential of each test chemical to affect genetic material. The test selection criteria focus on the test's ability to detect, with appropriate assay methods, the capacity of the chemical to alter genetic material in cells. When mutagenic potential is demonstrated, these findings are considered in the assessment of potential heritable effects in humans, in the weight-of-the-evidence evaluation for carcinogenicity, and in the decision to require submission of a carcinogenicity study if otherwise conditionally required.

Mutagenicity results per se are not used by themselves for risk assessment purposes, even when results suggest possible heritable genetic effects in humans. As described in Pesticide Assessment Guidelines: Subdivision F EPA, , the original mutagenicity test battery consisted of three assays: one for gene mutations, one for structural chromosome aberrations, and one for other genotoxic effects. Other testing included DNA damage and repair. The revised guidelines would require an initial battery of tests consisting of:. Results derived from these assays could trigger the requirement for further mutagenicity testing.

The type of additional required testing would depend on the observed results from the initial battery and other toxicity testing results. For example, testing could involve cytogenetic testing in spermatozoa if other test results suggest that they are targets. Data from studies on the absorption, distribution, bioaccumulation, excretion, and metabolism of a pesticide may also allow more meaningful evaluation of test results and more appropriate risk assessment as a result of more meaningful extrapolation from data on animals to humans.

Information on metabolites formed in laboratory animals is also used to determine whether further toxicity testing is required on plant metabolites. If a major metabolite forms in the plant but not in the test animal, separate toxicity testing on the plant metabolite could be necessary. The extent of testing required depends on the level of concern raised by the initial battery of toxicity tests acute and subchronic studies, one teratology study, and a battery of mutagenicity tests.

As presently designed, the metabolism study consists of four separate parts: a single low, intravenous dose of radiolabeled test material not required if the test material is insoluble in water or normal saline solution ; a single low, oral dose of radiolabeled test material; 14 consecutive daily low, oral doses of unlabeled test material followed by a single low dose of radiolabeled material; and single high, oral dose of radiolabeled test material.

Selection of the low dose is based on the NOEL. The high dose should elicit some signs of toxicity but not be so high that it results in mortality. The test species of choice is the rat. Bone, brain, fat, testes, heart, kidney, liver, lung, blood, muscle, spleen, residual carcass, and tissues showing pathology in this or prior tests should be examined for radioactivity for all animals except those given the intravenous dose.

This is done to determine if the test material or radiolabeled metabolite accumulates in any particular organ and to relate this information to the findings in toxicity studies. In addition, quantities of radiolabeled material in feces, urine, and expired air must be monitored for all dose groups at appropriate intervals up to 7 days after dosing. Furthermore, urinary and fecal metabolites must be identified. A metabolism study would also be required when significant adverse effects are observed in toxicology studies, including reproduction and developmental studies Guideline ; EPA, EPA is currently rewriting to guidelines for conducting metabolism studies and is including a tiered approach for study design and conduct.

Neurotoxicity studies are required to evaluate the potential of each pesticide to adversely affect the structure or function of the nervous. The objectives of these studies are to detect and characterize the following:. Results from these studies may be used for qualitative and quantitative risk assessment. The changes in the requirements for neurotoxicity testing were described above under ''Acute Toxicity" and "Subchronic Toxicity. EPA intends to develop better definitions of the conditions under which domestic animal safety Guideline ; EPA, testing and visual system studies Guideline ; EPA, would be required for all organophosphates and other pesticides shown to affect the visual system.

These studies could be of acute, subchronic, or chronic duration, whichever is deemed appropriate for the pesticide under study. Since guidelines have not been formulated for these studies, they will be designed in conjunction with EPA scientists. Current and past studies conducted by registrants are designed primarily to assess pesticide toxicity in sexually mature animals.

The protocols for these studies have evolved over several decades and have included some testing paradigms that allow extrapolation to infant and adolescent animals. These studies have produced some valuable information on toxicity and exposure. After reviewing EPA's current and proposed toxicity testing guidelines, however, the committee concluded that current studies do not directly address the following areas:.

Studies should be redesigned and expanded in scope to elucidate the differences in the metabolism and disposition of pesticides in the infant, adolescent, and young adult. Current metabolism studies are designed to provide information about sex-related differences, metabolic pathways and excretion, bioaccumulation in tissues, and tissue distribution in adult rats. EPA uses the data to determine whether toxicity testing needs to be conducted on individual plant or animal metabolites in addition to the parent compound.

The metabolism of pesticides in newborn animals needs to be more thoroughly investigated. Greater knowledge in this area would make it possible to develop computer programs for physiological pharmacokinetic modeling to forecast how information about metabolism in infant animals could be extrapolated to infant humans. The committee realizes that this is a very difficult area of investigation and application. Nevertheless, it urges that such investigations be pursued, since the resulting information could provide more realistic systemic exposure scenarios for risk assessment.

A study should be conducted to compare the toxicity of several representative classes of pesticides in both adult and immature animals. Results of such a broad-range study designed to specifically address the infant and young adult animal should indicate whether comparative studies of this nature should routinely be required by EPA. This study should be designed to examine several critical end points in the developing animal, including neural functional and behavioral , immune, and endocrine systems to cite a few examples.

Because the battery of acute toxicity tests now required by EPA is generally performed in adult animals, very little information is available on acute toxicity in immature animals. Such data are important in determining dietary risk to infants and children for acutely toxic pesticides such as organophosphates and carbamates. The committee recognizes that some of these data can be obtained from multigeneration studies if specific observation requirements are added to the current studies.

Test animals should be exposed to the chemical of concern early in their lives so the risks of exposure of infants and children to the compound can be more adequately assessed. The committee recognizes the difficulty in dosing animals during lactation and is aware that testing requirements would have to be modified to accomplish these studies.

Current reproduction studies Guideline ; EPA, partially address this period in the life of a rat, but the effects of early exposure are not addressed past 21 days of age for second-generation pups or past the death of the second-generation parents first-generation pups used for mating to produce the second generation. The protocol does not indicate whether exposure early in life has any impact on the adults or whether continuous exposure from birth to young adulthood influences the severity of the toxicity over a lifetime.

FDA has used the multigeneration studies to include the F 2 A or F 3 A generation of laboratory animals for direct and indirect food additives Becci et al. This would mean that weanlings from the F 1 A or F 2 A generation would be selected from each dose group and tested throughout their lifetimes see Table In addition to this group, another smaller group of rats from the F 1 generation would be killed at 6 months and 1 year and necropsied to examine the same parameters normally measured at the end of a lifetime feeding study.

The NTP tested three chemicals using a similar protocol and their standard protocol for an carcinogenicity study. One of the chemicals was ethylenethiourea, which is a breakdown product and metabolite of the ethylenebisdithiocarbamate fungicides and a thyroid toxicant decreases T3 and T4. In utero exposure did not affect the occurrence of liver tumors in male and female mice, but did result in a sex-dependent increase in the number of malignant thyroid tumors in mice and rats NTP, Although the thyroid is saved in these studies for microscopic examination and its weight is recorded, the committee believes that changes in the functioning capabilities of this organ can occur regardless of whether there are organ weight or histopathologic changes.

If abnormalities are found during histopathologic examination of the spleen, lymph nodes, thymus, and bone marrow, more detailed and specific studies should be conducted on a case-by-case basis relevant to the types of effects initially seen in immune system tests. EPA has developed protocols for immunotoxicity testing for some pesticides that affect the immune system, and the agency is considering developing a generic testing protocol. The committee believes that because the human immune system is one of the most robust of systems in terms of resistance to pesticides or other chemical toxicity, initial evaluation using current histopathologic examination of spleen, lymph nodes, thymus, and bone marrow should be sufficient unless abnormalities are noted.

One set of dams in this study would be dosed continuously with the test material from day 6 of gestation through birth of the pups and until weaning of their offspring at 21 days of age. A developmental assessment would be performed on the pups as described in EPA's recently published developmental neurotoxicity testing guidelines EPA, a. In addition, a set of pups from each dam would undergo gross and histopathologic examination at day 60 post partum.

The second set of dams would be dosed from day 6 of gestation to term; however, these animals would not be allowed to deliver but, rather, would be subjected to cesarean section as in a routine teratology study. The fetuses would be subjected to skeletal and visceral examination, as described for a teratology study Guideline designed to examine the prenatal development of pups.

This study design allows a determination of the reversibility of postnatal significance of findings seen in fetuses at the time of cesarean section. EPA has indicated in its proposed changes to Part that a similar study be required; however, the committee recommends that this study be made a requirement for registration of all food-use pesticides. Because neurotoxicity is such an important consideration for the newborn, EPA should continue to revise its published guidelines on developmental and functional neurotoxicity testing as new information emerges from the actual conduct of preregistration studies and from ongoing research in rodent neurotoxicity.

The committee supports EPA's proposed requirement for acute and subchronic neurotoxicity testing for pesticides and encourages the agency to make this a general requirement for all food-use pesticides—not just for organophosphate and carbamate pesticides. New approaches to neurotoxicity testing are described in the report Environmental Neurotoxicology NRC, EPA should develop a general guideline for visual system toxicity testing that can be modified and applied on a case-by-case basis.

The eye is exquisitely sensitive to changes in glucose metabolism, blood flow, and neuronal function, and several pesticides have been shown to be visual system toxicants hexachlorophene, naphthalene, 2,4-DNP, and some organophosphates. In the past, scientists have examined the effects of chemicals that may irritate the eye by accidental contact.

More recently, however, researchers have been examining the effects of chemicals on specific sections of the visual system, such as the optic nerve, iris, retina, and lens. The guideline proposed by the committee should be applied to species in which this type of testing appears to be appropriate, e. Recent studies indicate that visual system damage may be associated with dietary exposure to some cholinesterase inhibiting compounds. Thus the committee supports EPA's proposed testing the sensory evoked potential test of such pesticides for visual system toxicity.

However, it does not believe that a single protocol would suffice to cover all classes of compounds because different classes would affect different parts of the visual system. Armitage, P. The age distribution of cancer and multi-stage theory of carcinogenesis. Cancer — Becci, P. Voss, F.

Hess, M. Gallo, R. Parent, K. Stevens, and J. Long-term carcinogenicity and toxicity study of zearalenone in the rat. EPA U. Environmental Protection Agency. Revised Ed. November Washington, D. Addendum 10—Neurotoxicity. Addendum 9—Mutagenicity. Gad, S. Statistic for toxicologists. Hayes, ed. New York: Raven Press. Geneva, Switzerland: World Health Organization. Loomis, T. Philadelphia, Pa.

Issues in Risk Assessment. NTP TR Research Triangle Park, N. Weil, C. Guidelines for experiments to predict the degree of safety of a material for man. Many of the pesticides applied to food crops in this country are present in foods and may pose risks to human health. Current regulations are intended to protect the health of the general population by controlling pesticide use.

This book explores whether the present regulatory approaches adequately protect infants and children, who may differ from adults in susceptibility and in dietary exposures to pesticide residues. This book will be of interest to policymakers, administrators of research in the public and private sectors, toxicologists, pediatricians and other health professionals, and the pesticide industry. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

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Do you enjoy reading reports from the Academies online for free? Sign up for email notifications and we'll let you know about new publications in your areas of interest when they're released. Get This Book. Visit NAP. Looking for other ways to read this? No thanks. Pesticides in the Diets of Infants and Children.

Page Share Cite. The selection of animal species for toxicity tests depends on life span,. Guideline Rejection factor Developmental Toxicity—Nonrodents cont. Fenner-Crisp, EPA, personal communication, Not required if test material is a gas or highly volatile. Required if the active ingredient is a gas at room temperature or if use of the product results in respirable droplets and use may result in repeated inhalation exposure at a concentration likely to be toxic, regardless of whether the major route of exposure is inhalation EPA's Proposed Changes.

The objectives of these studies are to detect and characterize the following: effects on the incidence and severity of clinical signs, the alteration of motor activity, and histopathology in the nervous system following acute, subchronic, and chronic exposures; the potential of cholinesterase inhibiting pesticides and related substances to cause a specific organophosphate-pesticide-type induced delayed neurotoxicity; other neurotoxic effects based on screening studies on certain chemical classes; and effects on organisms exposed prior to birth or weaning.

This page in the original is blank. Login or Register to save! The committee focuses on four major areas: Susceptibility: Are children more susceptible or less susceptible than adults to the effects of dietary exposure to pesticides? Exposure: What foods do infants and children eat, and which pesticides and how much of them are present in those foods?

Is the current information on consumption and residues adequate to estimate exposure? Toxicity: Are toxicity tests in laboratory animals adequate to predict toxicity in human infants and children? Do the extent and type of toxicity of some chemicals vary by species and by age? Assessing risk: How is dietary exposure to pesticide residues associated with response?

How can laboratory data on lifetime exposures of animals be used to derive meaningful estimates of risk to children? Does risk accumulate more rapidly during the early years of life? Stay Connected! Developmental toxicity. Offspring: effects on viability, sex ratio, growth, behavior. Tumor development and general toxicity. Heritable lesions leading to altered phenotypes. Minimum No. Acute oral rat , dermal, or inhalation rat. Rat, — g; rabbit, 2. Reproduction rat c. Chronic toxicity 1 or 2 year rat. Oncogenicity lifetime rat and mouse. Acute Oral Toxicity Lack of characterization of the test material.

Inadequate dose levels to calculate LD Acute Dermal Toxicity Inadequate percentage of body surface area exposed. Improper number of animals tested per dose group. Omitted source, age, weight, or strain of test animal. Acute and Day Inhalation and Inadequate reporting of exposure methodology.

Chamber concentration not measured. Primary Dermal Irritation Dermal Sensitization Control problems Dosing level problems. Unacceptable protocol or other protocol problems. Individual animal scorers or data missing. Scoring method or other scoring problem. Reporting deficiencies or no quality assurance statement. Information on the pilot study and other problems associated with dose level selection An investigational parameter missing Information on the pilot study and other problems associated with dose level selection.

Lack of characterization of the test material Raw data analyses incomplete or missing A systemic NOEL was not established Inadequate percentage of body surface area exposed in each dose group Insufficient number of dose levels tested. Missing histopathology information Missing information in study reports MTD was not achieved Missing historical control data Lack of characterization of the test material Deficiencies in reporting the study data.

Carcinogenicity—Mice b. Histopathology information missing MTD was not achieved Lack of historical control data Information missing in study reports Lack of characterization of the test material Deficiencies in reporting of study data. Developmental Toxicity—Rodents a. Missing historical controls Lack of characterization of the test material Information missing or requiring clarification of the laboratories' methods Information missing or requiring clarification of the laboratories' results A NOEL was not established Statistical problems Did not use conventional assessments for skeletal or visceral examinations.

Developmental Toxicity—Nonrodents b.

Kidney Toxicological Assessment

Clarification of laboratory procedures of interpretation of the data Individual maternal or fetal data missing Missing historical controls Lack of characterization of the test material Excessive maternal toxicity. Developmental Toxicity—Nonrodents cont. Inadequate or missing data on identification of metabolites Improper methodology or dosing regimen Inadequate number of animals were used in the dose groups No individual animal data Improper reporting Inadequate or missing tissue residue analysis data Testing at only one dose level Only one sex of animal used Lack of an intravenous dose group No collection of 14 CO 2.

Data Requirements. Test Substance Data to Support. Higher Cd concentrations are found in hot spots related to human activities and on agricultural land where high amounts of phosphate fertilizers and manure are utilized [ 33 ]. The total concentrations of toxic elements found in the analysed kidneys were usually low and did not exceed the maximum permissible levels established by the Serbian legislation. Since vegetable foods constitute the major source of Cd for humans [ 1 , 34 ] it can be concluded that the levels of total toxic elements including Cd found in the tested kidneys do not represent an imminent toxicological risk to Serbian consumers.

However, it is very important to keep the measures necessary to maintain a steady control of the levels of these elements in staple food in the country in view of the potential health hazard that toxic elements represent. The pathomorphological examination results are summarized in Figures 1 — 3. N-number of pathohistological findings of renal tissues and co-incidence of toxic elements in kidney. In all 90 pigs were slaughtered during the study period. Kidneys from these pigs submitted to the laboratory were pale, swollen and enlarged with a change in color from the normal mahogany to tan, as follows: 43 The only macroscopic lesions observed in few cases were small grey-white foci on the kidney surface.

No obvious difference was observed between the right and left kidney. No significant changes were seen in other organs. The external surface of kidney in which Hg first four and Cd the last one were detected, are shown in Figure 1A , while, the external surface of kidney in which co-incidence of Hg and Cd 0. Histological examination of the kidneys showed two types of changes: degenerative-affecting epithelial cells in some proximal tubules of pigs, and proliferative changes in the interstitium.

Dystrophy moderate to marked degenerative changes, Figure 2C , swelling, vacuolization and lipidosi, were the main changes in the tubular epithelial cells. In the interstitium of some renal cortical regions, there was limited proliferation of connective tissue Figure 2D and focal infiltration of mononuclear inflammatory cells which was sometimes accompanied by small granulomas. Major renal histopathological changes.

Lipidosis of proximal tubule cells, renal hemorrhages, and swelling of proximal tubule cells were seen in 41 Vascular changes expresed as a hyperaemia of blood vessels was seen in 12 From a total of 56 analyzed kidneys samples in which the presence of toxic elements was found in 11 samples were determinet co-occurrence of Cd and Hg, while in only one samples is determined co-occurrence of Cd and As Figure 3. The kidney is clearly the major target organ of chronic Cd and Hg toxicity [ 35 — 38 ] Accumulated evidence also indicates that kidney is a target organ for As toxicity.

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Since kidney is the major organ for As elimination and most of the As is rapidly eliminated through the kidney [ 39 , 40 ], renal cells are, thus, exposed to a major portion of the absorbed As dose. After absorption, most of the toxic elements are accumulated in the liver where it induces the production of metallothioneins MT a family of low-molecular-weight metal-binding proteins that aid in the intracellular processing of metal ions [ 41 , 42 ].

Metallothioneins exist in most tissues, have a high cysteine content, and hence may be similar to metal chelators in providing heavy metal tolerance and regulating Hg distribution and retention [ 43 — 45 ]. Intracellular metallothionein has also been demonstrated to protect against metal-induced hematotoxicity and immunotoxicity [ 46 ]. Metallothionein has been utilized as a sublethal cellular indicator in fish for Hg exposure [ 47 ]. When the synthesis of MT becomes insufficient for binding all Cd ions in the liver, Cd not bound to MT produce hepatocyte injury and a Cd—MT complex is released into the bloodstream.

The complex in the plasma is then filtered through the glomeruli in the kidney and taken up by the proximal tubular cells [ 48 , 49 ]. Moreover, under certain conditions [e. The toxic effects of mercury on the kidney are well characterized and include acute tubular necrosis and reduced glomerular filtration rate.

In small doses, the S3 segment in the cortico-medullary area is the primary target site. As the dose of mercury is increased, the injury spreads to involve the S1 and S2 segments of the proximal tubules [ 51 ]. A more recent study has shown that Cd nephrotoxicity is also associated with alterations in the localization of the tight junction protein claudin-2 in the proximal tubule [ 52 ]. Additional studies have shown that N -cadherin and its associated proteins may be involved in the nephrotoxic responses to other metals such as Hg [ 36 , 53 ] and bismuth Bi [ 54 ].

Hg has a relatively large thiol association constant, thereby enabling this reaction [ 57 ]. Despite the thermodynamic stability of metal—SH complexes, they are generally kinetically labile, and hence are rapidly mobile in most biological systems [ 58 ]. Consistent with its thiol binding properties, Hg has been shown to preferentially distribute in the lysosomal fraction of rat cells [ 57 ] and interact with phospholipid membranes specifically phosphatidylserine and phosphatidylcholine [ 57 , 60 , 61 ]. Furthermore, while Hg can inhibit enzymes with SH groups, and interact with membrane proteins, it can also substitute for zinc in certain zinc-activated enzymes e.

The ability of Hg to interact with phospholipids and specific enzyme systems may help explain the cell degeneration, apoptosis and necrosis, and overall toxicity observed in immune system cells. In a study on the effects of inorganic Hg on cell membranes, Liang et al. Leong et al. These and other experimental animal studies demonstrate a wide range of biological effects from exposure to different species of Hg [ 67 — 70 ]. Enlarged kidneys are indicative of renal inflammation and proliferative lesions following chronic exposure to Cd [ 71 ] or As [ 72 ].

The increased kidney injury from Cd and As co-exposure might be due to increased oxidative stress. It has been proposed that both Cd [ 73 — 77 ] and As [ 76 , 77 ] may produce oxidative stress as a cellular mechanism of toxicity. Other recent studies have shown that alterations in the activity of focal adhesion kinase may play a key role in the malignant transformation of cells by arsenic [ 78 , 79 ]. In this regard, Cd and As co-exposure produces significantly more lipid peroxidation in liver and kidney than either inorganic given alone [ 80 ]. In regard to aetiology of porcine nephropathy, the production of multiple toxins as is sometimes the environmental situation, presents a problem that has not been sufficiently investigated.

Co-incidence of pathohistological findings of renal tissues and toxic elements in kidneys from slaughtered pigs are summarized in Figure 3. A total of 90 kidneys from healthy slaughtered swine from three different regions of Serbia were sampled during a six month period. The slaughtered pigs had an average weight of about kg and age of about six months. Sampling in the slaughterhouses consisted of collecting one kidney per pig, from five pigs per farm.

Visible fat, connective tissue and major blood vessels were excised and the samples were then homogenized. Kidney samples for instrumental analysis were prepared using the method of acid microwave digestion. Samples underwent digestion in a microwave digestion unit Milestone TC with temperature control. Mercury Hg concentrations in samples were analyzed by hydride generation atomic absorption spectrophotometry at Appropriate quality assurance procedures were carried out to ensure reliability of the results.


Samples were carefully handled to avoid contamination. Glassware was properly cleaned, and the reagents were of analytical grade. Double distilled deionised water was used throughout the study. Reagents blank determinations were used to correct the instrument readings. Quality control procedures included the analysis of a standard reference material BCR No.

Additional posttests were applied to evaluate differences among groups with statistically significant variation among means. Differences with p values smaller than 0. Thus, the consumption of average amounts of pork meat and meat byproducts which include internal organs liver, kidneys, heart, and lungs does not pose a health risk for the consumer. Despite the limited number of samples examined in the present study, it is important to notice that even the low levels of toxic elements concentration found in food, may contribute to the toxic elements daily intake.

The findings of this study suggests that regular surveys for toxic elements should be done on all food commodities in order to evaluate the possibility of health risks associated with toxic elements exposure, to assure food safety and to protect the consumers from food that might negatively affect their health. Regular surveys and monitoring programmes for toxic elements contents in foodstuffs have been performed for decades by several countries. In addition to toxicological assessment it is clearly evident from the studies of many authors and the findings of this study that interactions between toxic elements are very important in toxicology.

The kidneys are target organ for As, Cd, Hg toxicity. Long-term, even low-level, exposure to this metal leads to kidney damage characterized by tubular dysfunction. Future research should focus on the interactions between these elements in humans exposed to toxic elements occupationally and environmentally. The authors thank the Institute for the financial support. National Center for Biotechnology Information , U.

Published online Dec 8. Dragan R.

Nephrotoxicity (Renal Toxicity) - Managing Side Effects - Chemocare

Find articles by Dragan R. Verica B. Find articles by Verica B. Zoran I. Find articles by Zoran I. Author information Article notes Copyright and License information Disclaimer. Keywords: toxic elements, kidney, residue, pathomorphology, swine. Introduction Environmental pollution with toxic elements is a dangerous problem that is recognized worldwide. Results and Discussion 2. Incidence of Heavy Metals Regional variations in the occurrence of toxic elements in the kidneys of slaughtered pigs and the number of samples falling into specified concentration ranges are summarized in Table 1.

Table 1. Open in a separate window. Pathomorphology Examination The pathomorphological examination results are summarized in Figures 1 — 3. Figure 1. External surface of kidneys from which where Hg and Cd were detected. Figure 3. Gross pathology In all 90 pigs were slaughtered during the study period. Pathohistological examination Histological examination of the kidneys showed two types of changes: degenerative-affecting epithelial cells in some proximal tubules of pigs, and proliferative changes in the interstitium.

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Figure 2. Experimental Section 3. Sampling A total of 90 kidneys from healthy slaughtered swine from three different regions of Serbia were sampled during a six month period. Digestions Kidney samples for instrumental analysis were prepared using the method of acid microwave digestion. Quality Assurance Appropriate quality assurance procedures were carried out to ensure reliability of the results. References 1. A global perspective on cadmium pollution and toxicity in non-occupationally exposed population.

The heavy metal concentrations along roadside trees of Quetta and its effects on public health. Food Safety: Contaminants and Toxins. Jarup L. Hazards of heavy metal contamination. Essential heavy metals in environmental samples from western India. Heavy metals in ryegrass species versus metal concentrations in atmospheric particulates in an industrial area of southern Italy.

Understanding renal toxicity of heavy metals. Prenatal exposure to heavy metals: Effects on childhood cognitive skills and health status.

Environmental Health Criteria. Steenland K, Boffetta P. Lead and cancer in humans: Where are we now? Dolk H, Vrijheid M. The impact of environmental pollution on congenital anomalies. Schwartz J. Air pollution and daily mortality: A review and meta-analysis. Vascular effects of chronic arsenic exposure: A review. Ingested arsenic and internal cancer: A historical cohort study followed for 33 year.

Health effects of cadmium exposure a review of the literature and a risk estimate. Scamlintivittn J. Genetic toxicology of a paradoxical human carcinogen, arsenic: A review. Mutaliini Res. Abou-Arab AAK. Heavy metal contents in Egyptian meat and the role of detergent washing on their levels. Food Chem Toxicol. Arh Hig Rada Toksikol. Lead and cadmium levls in edible internal organs and blood of poultry chicken. Evaluation of Certain Food Additives and Contaminants.

Evaluation of certain food additives and contaminants. European Parliament and of the Council: Brussels, Belgium, Cadmium content in foodstuffs from the Greek market. Food Addit. Milacic R, Kralj B. Food Res. Hazardous Substances in the European Marine Environment. EFSA J. The influence of calcium content in diet on cumulation and toxicity of cadmium in the organism. Interactions between cadmium and zinc in the organism.

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