Suitable test concentration of cobalt and concomitant reactivity to nickel and chromium: A multicentre study from the Swedish Contact Dermatitis Research Group.

BACKGROUND: In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid-1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world. OBJECTIVES: To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co-occurrence of allergy to cobalt, chromium, and nickel. RESULTS: Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty-seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt-positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males. CONCLUSION: The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021.

Chronic dietary exposure to nickel from selected foods consumed in Belgium.

The risk assessment conducted by the European Food Safety Authority stated some concerns regarding the chronic exposure of the European population to nickel due to food intake. This study aimed to evaluate the extent of the Belgian population's exposure to nickel via intake of different foods/drinks available in their market. Ni concentrations were measured in selected foods consumed in Belgium, and exposures from this limited group of foods were estimated for consumers of these foods. Legumes, soy products, breakfast cereals, and chocolate spreads were responsible for 26%, 14%, 11% and 8% of the overall exposure (overall chronic exposure through consuming all the included food types in this study except tap water) of children (3-9 years) to nickel. For adolescents (10-17 years), the highest percentage of overall chronic exposure again originated from legumes (19%). This was followed by breakfast cereals (14%), soy products (11%) and chocolate spreads (11%). For adults (18-64 years), major contributors to the overall chronic daily exposure were legumes (16%), dark chocolate (15%) and breakfast cereals (10%). The aggregate exposure assessment, including the highest contaminated foods, for different sub-populations, revealed mean exposure levels of 1.02, 0.60 and 0.34 µg kg-1 b.w. day-1 for children, adolescents, and adults respectively. The mean, P75, P90 and P95 values for aggregate chronic exposure of the overall consumer's population were 0.62, 0.80, 1.5 and 210 µg kg-1 b.w. day-1 respectively. This study recommends controlling the intake of food products with elevated nickel content especially for the more vulnerable sub-population groups such as children with lower body weight and nickel sensitised individuals. It also demonstrates a shift in potential risk on human health to nickel exposure due to the transition towards a more plant-based diet.

A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses.

Adaptive features of natural killer (NK) cells have been reported in various species with different underlying mechanisms. It is unclear, however, which NK cell populations are capable of mounting antigen-specific recall responses and how such functions are regulated at the molecular level. Here, we identify and characterize a discrete population of CD49a+CD16- NK cells in the human liver that displays increased epigenetic potential to elicit memory responses and has the functional properties to exert antigen-specific immunity in the skin as an effector site. Integrated chromatin-based epigenetic and transcriptomic profiling revealed unique characteristics of hepatic CD49a+CD16- NK cells when compared with conventional CD49a-CD16+ NK cells, thereby defining active genomic regions and molecules underpinning distinct NK cell reactivity. In contrast to conventional NK cells, our results suggest that adaptive CD49a+CD16- NK cells are able to bypass the KIR receptor-ligand system upon antigen-specific stimulation. Furthermore, these cells were highly migratory toward chemokine gradients expressed in epicutaneous patch test lesions as an effector site of adaptive immune responses in the skin. These results define pathways operative in human antigen-specific adaptive NK cells and provide a roadmap for harnessing this NK cell subset for specific therapeutic or prophylactic vaccine strategies.

Exposure to variable doses of nickel oxide nanoparticles disturbs serum biochemical parameters and oxidative stress biomarkers from vital organs of albino mice in a sex-specific manner.

INTRODUCTION: This study was designed to report the biological effect of nickel oxide nanoparticles (NiO NPs) in albino mice. MATERIAL AND METHODS: Five weeks old albino mice of both sex were intraperitoneally injected either with 20 mg (low dose) or 50 mg/mL saline/kg body weight (high dose) of NiO NPs for 14 days. Saline-treated controls were maintained in parallel. Complete blood count, selected serum biochemical parameters and oxidative stress biomarkers from vital organs were determined in all subjects. RESULTS: Male mice treated with NiO NPS had increased blood urea nitrogen, elevated superoxide dismutase (SOD) in liver elevated MDA in liver, kidney and heart and reduced catalase activity in heart and kidney. Female mice treated with NiO NPs had significantly reduced serum albumin and total proteins, SOD in lungs and elevated MDA in liver. DISCUSSION: We are reporting that intraperitoneal injections of NiO NPs for 14 days drastically affect blood serum parameters and oxidative stress biomarkers from vital organs of albino mice. CONCLUSION: Toxic effects of NiO NPs were dose and sex dependent and they were more pronounced at higher dose and in male mice.

Dietary exposure of the Italian population to nickel: The national Total Diet Study.

Dietary exposure of the Italian population to nickel has been assessed in the national Total Diet Study (TDS). Occurrence data were combined with national individual consumption data to estimate mean and high level dietary exposure of population subgroups according to age and gender, both at the national level and for the four main geographical areas of Italy. The mean chronic dietary exposure of infants and toddlers, children, adolescents, adults, and the elderly were 4.00, 4.57, 2.57, 1.55, and 1.47 µg/kg bw per day, respectively. These intakes lie in the intermediate range of exposure estimates from TDS carried out in other countries. Main contributors to the total nickel exposure for children and adolescents were 'sweet products' and 'cereals and cereal products'. In adults and the elderly nearly 30% of the exposure was associated to the consumption of 'cereals and cereal products'. Mean and 95th percentile chronic dietary exposure was below the TDI in all age groups. For the risk characterisation of acute oral exposure, exposure data for consumers only in the adult population were compared with the reference point for systemic contact dermatitis. Consumption of 'cocoa', 'chocolate', 'crustaceans and molluscs', 'pulses' had remarkable potential to elicit adverse effects in nickel-sensitised individuals.

Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading.

Suprabasin (SBSN) is expressed not only in epidermis but also in epithelial cells of the upper digestive tract where metals such as nickel are absorbed. We have recently shown that SBSN level is decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn-/-) mice, this study was conducted to investigate the outcome of SBSN deficiency in relation to AD. Sbsn-/- mice exhibited skin barrier dysfunction on embryonic day 16.5, but after birth, their barrier function was not perturbed despite the presence of ultrastructural changes in stratum corneum and keratohyalin granules. Sbsn-/- mice showed a comparable ovalbumin-specific skin immune response to wild type (WT) mice and rather lower contact hypersensitivity (CHS) responses to haptens than did WT mice. The blood nickel level after oral feeding of nickel was significantly higher in Sbsn-/- mice than in WT mice, and CHS to nickel was elevated in Sbsn-/- mice under nickel-loading condition. Our study suggests that the completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes nickel absorption and high CHS to nickel, sharing the features of intrinsic AD.

Severe systemic delayed dermatitis in a patient with nickel-titanium sterilization microinserts perforating the uterus.

We report a case of severe systemic delayed dermatitis in a patient with nickel-titanium sterilization microinserts placement complicated by uterine perforation and polyethylene terephthalate (PET) exposure. We hypothesize that delayed dermatitis may be caused by the exposure of PET fibers in this patient with underlying autoimmune disorder. Further research on the use of PET and the potential of systemic dermatologic reactions when exposure occurs is needed, especially when considering the inclusion of PET in future implant device development.

CuS-NiS2 nanomaterials for MRI guided phototherapy of gastric carcinoma via triggering mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vivo without obvious side effects. We revealed that CuS-NiS2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS2, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

The Effects of Low-Nickel Diet Combined with Oral Administration of Selected Probiotics on Patients with Systemic Nickel Allergy Syndrome (SNAS) and Gut Dysbiosis.

BACKGROUND: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by systemic nickel allergy syndrome (SNAS), including gastrointestinal symptoms, which in turn are associated with gut dysbiosis. We evaluated the effects of a low-Ni diet alone or in combination with the oral consumption of appropriate probiotics on Ni-sensitivity and urinary dysbiosis markers in SNAS patients. METHODS: n = 51 patients with SNAS and concomitant intestinal dysbiosis were enrolled in the study. According to the urinary indican/skatole levels, quantified through a colorimetric and a high-performance liquid chromatographic method, respectively, patients were assigned to a dysbiosis type/grade and followed a low-Ni diet for three months. Along with the diet, 22 patients also consumed probiotics based on the dysbiosis type. In particular, a Lactobacilli- or Bifidobacteria-containing formulation was administered to patients with fermentative or putrefactive dysbiosis, respectively, while a broad-spectrum probiotic formulation containing both Lactobacilli and Bifidobacteria was administered to patients with mixed dysbiosis. After three months, patients were invited to repeat the Ni-stimulation and the dysbiosis tests. RESULTS: The fermentative dysbiosis group represented the largest group followed by the mixed dysbiosis group, while only two patients had putrefactive dysbiosis. Overall, at three months of treatment in general (diet alone with or without probiotics), the Ni-sensitivity and dysbiosis levels were strongly ameliorated. The association of a low-Ni diet with a specific probiotic oral supplementation was significantly more effective in decreasing dysbiosis levels or reaching eubiosis than with diet alone. CONCLUSION: Our results, while confirming the benefits of a low-Ni diet in SNAS patients, strongly support that appropriate adjuvant treatment with probiotics significantly helps to improve intestinal dysbiosis or restore a healthy microbiota.

Gene expression in mouse muscle over time after nickel pellet implantation.

The transition metal nickel is used in a wide variety of alloys and medical devices. Nickel can cause a range of toxicities from allergy in humans to tumors when implanted in animals. Several microarray studies have examined nickel toxicity, but so far none have comprehensively profiled expression over an extended period. In this work, male mice were implanted with a single nickel pellet in the muscle of the right leg with the left leg used as a control. At 3 week intervals up to 12 months, nickel concentrations in bioflulids and microarrays of surrounding tissue were used to track gene expression patterns. Pellet biocorrosion resulted in varying levels of systemic nickel over time, with peaks of 600 µg L-1 in serum, while global gene expression was cyclical in nature with immune related genes topping the list of overexpressed genes. IPA and KEGG pathway analyses was used to attribute overall biological function to changes in gene expression levels, supported by GO enrichment analysis. IPA pathways identified sirtuin, mitochondria, and oxidative phosphorylation as top pathways, based predominantly on downregulated genes, whereas immune processes were associated with upregulated genes. Top KEGG pathways identified were lysosome, osteoclast differentiation, and phasgosome. Both pathway approaches identified common immune responses, as well as hypoxia, toll like receptor, and matrix metalloproteinases. Overall, pathway analysis identified a negative impact on energy metabolism, and a positive impact on immune function, in particular the acute phase response. Inside the cell the impacts were on mitochondria and lysosome. New pathways and genes responsive to nickel were identified from the large dataset in this study which represents the first long-term analysis of the effects of chronic nickel exposure on global gene expression.

Biochemical, Toxicological, and Histopathological outcome in rat brain following treatment with NiO and NiO nanoparticles.

Nickel oxide nanoparticle (NiO NPs) has been widely used in various fields such as catalysts, radiotherapy, and nanomedicine. The aim of this study was to compare the effects of nickel oxide (NiO) and NiO NPs on oxidative stress biomarkers and histopathological changes in brain tissue of rats. In this study, 49 male rats were randomly divided into one control group and 6 experimental groups (n = 7). The control group received normal saline and the treatment groups received NiO and NiO NPs at doses of 10, 25, and 50 mg/kg intraperitoneally for 8 days. After 8 days, animal was sacrificed, brain excised, homogenized, centrifuged, and then supernatant was collected for antioxidant assays. The results showed that activity of GST in NiO NPs groups with doses of 10, 25, and 50 mg/kg (79.42 ± 4.24, p = 0.035; 78.77 ± 8.49, p = 0.041; 81.38 ± 12.39, p = 0.042 to 47.26 ± 7.17) and catalase in NiO NPs groups with concentrations of 25 and 50 mg/kg (69.95 ± 8.65 to 39.75 ± 5.11, p = 0.02) and (68.80 ± 4.18 to 39.75 ± 5.11 p = 0.027) were significantly increased compared with the control, respectively. Total antioxidant capacity in NiONPs group with doses of 50 mg/kg was significantly decreased (345.00 ± 23.62, p = 0.015 to 496.66 ± 25.77) compared with control. The GSH level in all doses NiO and NiONPs was significantly decreased compared with the control (p = 0.002). MDA level in NiONPs and NiO groups with doses of 50 mg/kg was significantly increased (13.03 ± 1.29, p = < 0.01; 15.61 ± 1.08, p = < 0.001 to 7.32 ± 0.51) compared with the control, respectively. Our results revealed a range of histopathological changes, including necrosis, hyperemia, gliosis, and spongy changes in brain tissue. Thus, increasing level of MDA, GST, and CAT enzymes and decreasing GSH and TAC and also histopathological changes confirmed NiONPs and NiO toxicity.

The Association Between Thyroid Injury and Apoptosis, and Alterations of Bax, Bcl-2, and Caspase-3 mRNA/Protein Expression Induced by Nickel Sulfate in Wistar Rats.

To study the toxicity induced by Nickel sulfate (NiSO4) on thyroid tissue, and investigate the role of apoptosis as the possible mechanism, thirty-two male Wistar rats were randomly divided into control group (normal saline, ip), low dose group (2.5 mg/kg day NiSO4, ip), middle dose group (5 mg/kg day NiSO4, ip), high dose group (10 mg/kg day NiSO4, ip). After 40 consecutive days of treatment, there were obvious pathological changes in the thyroids of high dose group. Free T4 (FT4) and thyroid-stimulating hormone (TSH) were significantly lower in the NiSO4-treated groups than those in the control group (F = 4.992, p = 0.016; F = 4.524, p = 0.012). The mRNA expression of Caspase-3 was significantly higher (F = 10.259, p = 0.014) in all NiSO4-treated groups, and the mRNA expression of Bcl-2 was significantly lower (F = 9.225, p = 0.018) only in the high dose group. Both control group and the NiSO4-treated groups showed no changes in the mRNA expression of Bax gene. The ratio of Bcl-2/Bax decreased with the increase in exposure dose of NiSO4 (F = 13.382, p = 0.015). The mRNA expression of Fas went up in high dose group (F = 66.632, p < 0.001). The Caspase-3, Fas, and the Bax protein expressions measured by immunohistochemistry were consistent with the mRNA expression. The expression of Bcl-2 protein was significantly lower in the test groups than in the control group (F = 3.873, p = 0.025). NiSO4 as an Endocrine Disrupting Chemical may induce the thyroid injury through apoptosis and lead to hypothyroidism. Also, apoptosis in thyroid tissues was closely related to the alternations of Caspase-3, Bcl-2, and Fas mRNA and protein expression.

A seven-year retrospective analysis of patch test data in a cohort of patients with contact dermatitis in Sri Lanka.

BACKGROUND: Patch testing with a baseline series is a common tool employed when the sensitizing agent in contact dermatitis is unclear. However, for Asian countries, there are no locally validated baseline series to utilize in screening. METHODS: We completed a retrospective analysis of all patients that had undergone patch testing with the European Baseline series, Shoe Series or Comprehensive International Baseline series, over 7 years from 2012 to 2018 in a tertiary care reference dermatology clinic in Sri Lanka to evaluate the suitability of these investigations to identify causes for contact dermatitis in the local study population. RESULTS: Out of 438 patients tested, 239 (54.8%) reacted to at least one substance in the series. The Shoe Series was significantly more likely to yield a positive result than the European Baseline Series (70.2% vs 46.9%, p < 0.05). The top three sensitizers identified by all series were nickel sulfate (16%, 70/438), p-phenylenediamine (12.3%, 54/438) and 2-mercaptobenzothiazole or mercapto mix (10.5%, 46/438). CONCLUSION: Shoe series has a comparatively high yield in the local population compared to European Baseline series. Since little less than half of the study population did not have any reactivity to any of the allergens tested it is important to develop or modify and validate a locally relevant, more suitable baseline series which is based on the Shoe Series in Sri Lanka. This is further evidence for the continuously changing nature of allergens in the environment and the need to modify existing patch testing standards accordingly.

Nickel oxide nanoparticles cause substantial physiological, phytochemical, and molecular-level changes in Chinese cabbage seedlings.

Nickel oxide nanoparticles (NiO NPs) are utilized in various industries and their release into the environment may lead to the pollution of agricultural areas. However, assessing the toxicity of NiO NPs in major food crops is difficult due to the limited information available on their toxicity. The present investigation was carried out to evaluate how NiO NPs affect plant growth, photosynthetic efficiency, and phytochemical content, as well as changes at the transcriptional level of these phytochemicals in Chinese cabbage seedlings. Chlorophyll, carotenoid, and sugar contents were reduced, while proline and the anthocyanins were significantly upregulated in NiO NPs-treated seedlings. The levels of malondialdehyde, hydrogen peroxide, and reactive oxygen species, as well as peroxidase (POD) enzyme activity, were all enhanced in seedlings exposed to NiO NPs. The levels of glucosinolates and phenolic compounds were also significantly increased in NiO NPs-treated seedlings compared to control seedlings. The expression of genes related to oxidative stress (CAT, POD, and GST), MYB transcription factors (BrMYB28, BrMYB29, BrMYB34, and BrMYB51), and phenolic compounds (ANS, PAP1, and PAL) were significantly upregulated. We suggest that NiO NPs application stimulates toxic effects and enhances the levels of phytochemicals (glucosinolates and phenolic compounds) in Chinese cabbage seedlings.

Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: a histological and biochemical perspective.

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28-day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co-operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose-dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose-dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo.

Oral Nickel Changes of Intestinal Microflora in Mice.

Nickel, a silver-colored metal found in nature, is a common cause of allergic contact dermatitis. Nevertheless, the existence of inflammatory reaction to oral nickel exposure remains controversial. The following study investigates whether oral nickel can change the intestinal microflora in mice. A total of 20 female ICR mice were randomly divided into two groups: the oral nickel group (Group O) and the control group (Group C). Group O received water containing 400 µM NiSO4·6H2O, while group C was given pure water for 21 days. The content of nickel in the kidneys was determined by atomic absorption spectrophotometry, while the composition of bacterial community in the cecum was detected by 16S rDNA sequencing. The results were subsequently validated by real-time quantitative PCR with genus and species specific primers. Compared to Group C, significantly higher nickel levels were observed in Group O (P = 0.016); however, our data suggested that oral administration of 400 µM NiSO4·6H2O was nontoxic to the animals. (No statistical difference in body animal weight was found between Group O and Group C, before and after oral administration of nickel.) At the genus level, significantly higher relative abundance of Bacteroides (P = 0.016) and Intestinimonas (P = 0.018), and significantly lower relative abundance of Lachnospiraceae_NK4A136_group (P = 0.002) and Lachnospiraceae_UCG-001_group (P = 0.042) were observed in the oral nickel group compared to the control group. In addition, Group O had significantly lower ratio of Firmicutes/Bacteroides (P = 0.008). The results of real-time quantitative PCR further confirmed that the amplicon mass of Bacteroides and B. fragilis in the Group O was significantly higher compared to C group (P = 0.034 and P = 0.02). Oral nickel could change the intestinal microflora in mice, thus suggesting that oral nickel alters the interaction between the host and the intestinal flora.

Experience in patch testing: A 6-year retrospective review from a single academic allergy practice.

BACKGROUND: Patch testing is the "gold standard" to identify culprit allergen(s) causing allergic contact dermatitis (ACD), but there are limited studies of patch testing from allergy practice settings. OBJECTIVE: We sought to explore patch test findings in a large academic allergy practice, including patch testing results, history of atopy, location of dermatitis, and referral source. We also wanted to determine whether patch testing using an extended panel, such as the North American screening series, compared with a limited series, such as the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) Test, increased the sensitivity. METHODS: A retrospective chart review was conducted of patients referred for patch testing over a 6-year period. RESULTS: A total of 585 patients (mean age 48.7 years, 71.6 % female) underwent patch testing over the 6-year period, of which 369 (63%) had a positive test. Of those who tested positive, 202 (55%) reported a history of atopy. The extremities were the most commonly involved site, followed by the head/neck and trunk. The 5 most common positive allergens were nickel sulfate, gold sodium thiosulfate, methylchloroisothiazolinone, thimerosal, and bacitracin. Three hundred fourteen (53.6%) patients were positive to at least 1 allergen on TRUE testing. Extended screening series identified an additional 10.8% of patients with positive tests who were negative to T.R.U.E. test allergens. CONCLUSION: Patch testing is a valuable diagnostic tool for the practicing allergist and provides early identification of culprit allergens in ACD. Performing an extended screening series such as the North American Contact Dermatitis Group (NACDG) or supplemental panel of allergens increased sensitivity when compared with a limited series.

Dietary Intake of Cadmium, Chromium, Copper, Nickel, and Lead through the Consumption of Meat, Liver, and Kidney and Assessment of Human Health Risk in Birjand, Southeast of Iran.

This study aimed to evaluate the mean concentration of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), and lead (Pb) in the meat and offal of cow and sheep. Also, the estimated daily intake (EDI) and health risk of these metals were calculated. Analysis of metals was undertaken by the use of an inductively coupled plasma-optic emission spectroscopy (ICP-OES). All samples were contaminated with all metals. Principal component analysis (PCA) showed a clear differentiation of cow and sheep in both the kidney and liver samples. In the liver and kidney, level of Cd, Cu, and Pb were positively correlated. The highest target hazard quotients (THQs) were calculated for Pb. Cd level in cow kidney had the highest carcinogenic rate (CR). Although, hazard index (HI) was lower than one, consumption of muscle especially in children should be noticed in both national and international consumers due to higher level of HI.