Use Of Zinc Supplementation Research Articles

Effects of Perioperative Zinc Supplementation on Copper Circulating Levels and Expression of Metallothionein and Copper Antioxidant Chaperone-1 in Leukocytes in Patients Undergoing CABG Surgery.

The use of zinc supplement may have a negative effect on copper status. The objective of this study was to evaluate the effect of zinc and vitamin E supplementation on copper and zinc biomarkers in patients undergoing coronary artery bypass graft (CABG) surgery. The study was an add-on project to a previously published randomized controlled trial (NCT05402826) on patients undergoing CABG surgery. Patients in the zinc-vitamin E group (n = 40) received oral zinc (120 mg) and vitamin E (1200 international units) 1 day before surgery, followed by 30 mg of zinc and 200 units of vitamin E per day until 21 days after surgery, while those in the control group (n = 38) received placebo. Plasma levels of copper, ceruloplasmin, superoxide dismutase (SOD) activity, as well as leukocyte gene expression of metallothionein 2A (MT2A) and antioxidant protein 1 (ATOX1), were determined 3 and 21 days after surgery. The plasma copper level in the zinc-vitamin E group was significantly lower than the placebo group on the 3rd postoperative day, but no significant between-group differences were observed on day 21. Plasma ceruloplasmin concentration and SOD activity were not different. Relative mRNA expression of leukocyte MT2A was increased at both times (days 3 and 21 in the zinc-vitamin E group compared to placebo, but ATOX1 expression was not affected. Although the plasma copper level was transiently decreased early after surgery in the zinc-vitamin E group, considering the lack of change in other copper biomarkers, it seems that the use of zinc supplements at the dose used in the present study does not have a significant negative effect on the role of intracellular copper.

Effectiveness of zinc supplementation on the incidence of oral mucositis during chemotherapy and radiation: A meta‑analysis.

Oral mucositis (OM) is a commonly observed and debilitating side effect of chemotherapy and radiation therapy in patients with cancer, especially head and neck cancer. Although there is no proven therapy for the prevention and treatment of OM, zinc supplementation effectively decreases the incidence of OM. This paper provides a current and comprehensive meta-analysis of the efficacy of zinc compared with placebo/control in OM. A systematic literature review was conducted using MEDLINE and Central databases for randomized control trials (RCTs) comparing zinc supplementation (oral or rinse) with placebo/control in patients with various types of cancer undergoing chemotherapy, radiation therapy or combined chemo-radiation. The outcome was OM incidence, independent of the severity. A random-effects model was used to calculate the pooled risk ratio and subgroup analyses were performed. A total of 12 RCTs were included, containing information from 783 patients. A decrease in OM incidence was observed overall when all cancer therapies were considered. However, subgroup analyses showed that zinc did not significantly decrease the incidence of OM when studies were stratified by cancer therapy or scale/criteria used to assess OM. The results of the meta-analysis support the use of zinc supplementation in decreasing OM incidence in patients with cancer receiving chemotherapy or radiation therapy. However, the high heterogeneity between studies and the small number of studies are limitations of the meta-analysis.

Is there RCT evidence to support the use of zinc supplementation in children for preventing mortality, morbidity, and growth failure?

Is there RCT evidence to support the use of zinc supplementation in children for preventing mortality, morbidity, and growth failure?

The Journal of Urology® Home Study Course 2023 Volume 209/210.

The Journal of Urology® Home Study Course 2023 Volume 209/210.

Post-diagnostic Zinc Supplement Use and Prostate Cancer Survival Among Men With Nonmetastatic Prostate Cancer.

Biological and experimental evidence support restoration of normal zinc levels in malignant prostate cells as a promising prostate cancer treatment, yet the influence of zinc supplementation after diagnosis on prostate cancer survival in a human population is unknown. We prospectively assessed post-diagnostic zinc supplementation in relation to prostate cancer survival among 5,788 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2019). We used Cox regression models to estimate the multivariable hazard ratios and 95% confidence intervals of lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality according to post-diagnostic zinc supplement use and dosage. During a median follow-up of 11 years, we documented 527 lethal prostate cancer events and 3,198 all-cause deaths. Fifteen percent of men reported zinc supplement use post-diagnosis. Compared to nonusers, post-diagnostic zinc supplement use was associated suggestively with a lower risk of lethal prostate cancer (HR [95% CI], 0.82 [0.60-1.13]) and significantly with all-cause mortality (0.84 [0.74-0.96]). The inverse association was mostly observed among men who used post-diagnostic zinc supplements of 1-24 mg/d (lethal prostate cancer: 0.55 [0.32-0.96]; all-cause mortality: 0.77 [0.64-0.93]), while higher dosage did not show a lower risk. Post-diagnostic low-dose zinc supplement use among nonmetastatic prostate cancer patients was associated with lower risk of lethal prostate cancer and all-cause mortality. A potential benefit of low-dose post-diagnostic zinc supplement for prostate cancer survival merits further study.

Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study.

Zinc supplementation was hypothesized to have therapeutic potential against prostate cancer, but its influence on prostate cancer incidence especially at high doses is controversial. A total of 47,240 men from the Health Professionals Follow-up Study were followed from 1986 to 2016. Men reported their zinc supplement use at baseline and biennially thereafter. Clinical features of prostate cancer included stage, grade, lethal and aggressive (T4 or N1 or M1 or Gleason 8-10) outcome. Multivariable Cox proportional hazards models were used to evaluate the association between zinc supplement use and incidence of prostate cancer. During a median follow-up of 28.3 years, we documented 6,980 incident prostate cancer cases including 1,053 lethal and 1,143 aggressive. Zinc supplement use was not associated with overall, localized, low- and intermediate-grade prostate cancer. However, compared to never-users, men who used supplement zinc more than 75mg/day were at higher risk for lethal (HR: 1.76, 95% CI: 1.16-2.66, Ptrend = 0.001) and aggressive prostate cancer (HR: 1.80, 95% CI: 1.19-2.73, Ptrend = 0.006). Similarly, men who took supplemental zinc for 15 or more years had a higher risk for lethal (HR: 1.91, 95% CI: 1.28-2.85, Ptrend <0.001) and aggressive prostate cancer (HR: 1.55, 95% CI: 1.03-2.33, Ptrend = 0.004). Zinc supplementation of more than 75mg per day or over 15 years may substantially increase risk of lethal and aggressive prostate cancer. Caution is warranted regarding excessive usage of zinc supplements among adult men.

Possible relationship between poor skin disorders prognosis and serum zinc level: A narrative review.

Zinc is a trace nutrient essential for the normal growth and development of human body. The main aim was to evaluate the significant association between measured zinc status in relation to different skin disorders and their severity. PubMed®, Google® Scholar™ and Cochrane© Reviews databases were searched for studies from January 2017 to June 2021, using the terms; zinc serum levels, zinc plasma levels and different dermatosis in the review, only human studies in English language were reviewed and the studies designs were controlled, cross sectional, observational and analytic types. A total of forty-eight research studies were included in this review. All studies have evaluated serum zinc in skin diseases including psoriasis, atopic dermatitis, pityriasis alba, androgenetic alopecia areata, telogen effluvium, vitiligo, melasma, acne, seborrheic dermatitis and hidradenitis suppuritiva. It was found that 33 studies had validated statistically significant differences in serum zinc levels between patients and controls. There is a predominance of low serum zinc levels in all the dermatoses reviewed. The clinical significance of this finding highlights the possible value, and need to investigate, the use of Zinc supplementation as an adjuvant therapy in the management of chronic inflammatory and autoimmune skin diseases proven to manifest altered zinc levels.

Major trace elements and their binding proteins in the early phase of Covid-19 infection.

Metal ions seem to play important roles in the pathogenesis of the novel coronavirus disease of 2019 (Covid-19) and are under investigation as potential prognostic markers and supplements in therapeutic procedures. The present study was aimed at assessing the relationship between the most abundant essential microelements (iron, zinc and copper) and their major binding proteins in the circulation in the early stage of infection. The concentration of zinc ions was measured to be higher in infected than in healthy persons, as well as ratios zinc/albumin and zinc/alpha-2-macroglobulin. Increased zinc levels could be attributed to cellular redistribution of zinc ions or to a use of zinc supplementation (zinc concentration was above the upper reference limit in one-third of infected individuals). Immunoblot analysis of protein molecular forms revealed that infected persons had greater amounts of proteinase-bound alpha-2-macroglobulin tetramer and albumin monomer than healthy individuals. The quantities of these forms were correlated with the concentration of zinc ions (r = 0.42 and 0.55, respectively) in healthy persons, but correlations were lost in infected individuals, most likely due to very high zinc concentrations in some participants which were not proportionally followed by changes in the distribution of protein species. Although we still have to wait for a firm confirmation of the involvement of zinc in beneficial defense mechanisms in patients with Covid-19, it seems that this ion may contribute to the existence of circulating protein forms which are the most optimal.Graphical abstract

Zinc Homeostasis in Diabetes Mellitus and Vascular Complications.

Oxidative stress represents an impaired metabolic system that promotes damage to cells and tissues. This is the predominant factor that leads to the development and progression of diabetes and diabetic complications. Research has indicated that zinc plays a consequential mechanistic role in the protection against oxidative stress as zinc is required for the proper functioning of the antioxidant system, the suppression of inflammatory mediators, and the modulation of zinc transporters. Recently, the mechanisms surrounding ZnT8, ZIP7, and metallothionein have shown to be of particular pathogenic importance and are considered as potential therapeutic targets in disease management. The literature has shown that zinc dysregulation is associated with diabetes and may be considered as a leading contributor to the deleterious vascular alterations exhibited by the disease. Although further investigation is required, studies have indicated the favorable use of zinc supplementation in the protection against and prevention of oxidative stress and its consequences over the course of the condition. This review aims to provide a comprehensive account of zinc homeostasis, the oxidative mechanisms governed by zinc status, current therapeutic targets, and the impact of zinc supplementation in the prevention of disease onset and in mitigating vascular complications.

A Randomized Clinical Trial of the Effect of Zinc Supplement on Depression and Anxiety in the Elderly

Background: Anxiety and depression in the elderly are considered important mental disorders. Objective: This study was designed to determine the effect of zinc Supplementation on depression and anxiety in the elderly. Methods: This study was a parallel randomized clinical trial. A total of 150 elderly aged 60 years and older were allocated into intervention and control groups by using the quadruple blocking method. The elderly in the intervention group received a daily dose of 30 mg zinc supplementation pill for 70 days and the elderly in the control group did not receive this supplement. Depression and anxiety in the elderly were measured using the Geriatric Depression Scale and the Beck Anxiety Inventory, respectively. A significance level of 0.05 was considered for all statistical tests. Results: After the intervention, the mean scores of depression and anxiety in the elderly were significantly decreased in the intervention group, as compared with the control group. Moreover, after the intervention, the serum zinc level in the elderly was significantly increased in the intervention group, as compared with the control group (P&lt;0.05). Conclusion: The use of zinc supplements improved depression and anxiety in the elderly. Therefore, it is recommended to use zinc supplements as a new therapeutic strategy for the prevention and treatment of depression and anxiety in the elderly. Registration No: This research was registered in the Iranian clinical trial system with code IRCT2017071635110N1.

Effectiveness of Structured Teaching Programme on the Knowledge of Mothers Regarding the use of Zinc Supplementation in the Management of Diarrhea among the under Five Children in Selected Rural Areas of Indore, MP

The present study was semi exploratory survey type of study. The data was gathered using a pretest and post test approach. Subjects or mothers were selected using purposive sampling technique method. 40 samples were selected for the present study. The survey was done by the researcher to evaluate the information especially with respect to the advantages of zinc supplementation and to get organized information and to provide a structured teaching program regarding the benefits of zinc in the diarrheal disease. The mean pre test score of the study was around 11.95 which were increased to 20.33 in the posttest. This reveals the effectiveness of structured teaching programme. The difference between the pre test and post test was found to be very highly significant, which was evident by the paired t test value 13.60. The chi square was test also done to find out the significant association between the socio demographic characteristics and the knowledge score. There was no significant association between the demographic characteristics and the knowledge score when compared with age, number of kids, occupation, monthly family income, and religion. Significant association was found especially between the instructive status of mothers and the knowledge score 9.95. The findings of the present study concludes that the structured teaching programme with respect to the zinc supplementation in the pre test was very less which was improved drastically in the posttest. Structured teaching programme was found to be really very effective which is evident by the post test score. The findings of the data also reveals that the structured teaching programme is viable system of providing data and helps in the improvement in the knowledge of the mothers.

Значение цинка при инфекционных заболеваниях у детей

Цинк играет разные роли в различных биологических процессах и имеет важное значение в росте клеток, дифференцировке клеток и обмене веществ. Его дефицит ассоциируется с нарушением роста и развития у детей, а также с нарушениями иммунитета и повышенной восприимчивостью к инфекциям. Согласно данным ВОЗ, тяжелый дефицит цинка у людей встречается редко, но дефицит легкой и умеренной степени широко распространен во всем мире. В этом обзоре обобщены данные о влиянии цинка на иммунную систему, его роли в воспалении и аспектах клинического использования. Клиническое применение препаратов цинка у детей с инфекционными заболеваниями направлено в основном на коррекцию дефицита и, следовательно, на повышение иммунного ответа. На сегодняшний день имеются доказательства эффективности применения препаратов цинка для лечения и профилактики инфекций верхних дыхательных путей, а также кишечных инфекций.

A Study to Assess the Knowledge of Women regarding use of Zinc Supplementation with ORS in Managing Diarrhoea in a Selected Rural Community in Bhopal

Background:Diarrhoea is the third most common reason for youth mortality in India. More than 2 million kids die because of loose bowels and parchedness consistently. Diarrhoeal sickness causes hefty monetary pressure on the healthcare administration. Much consideration has been given to diarrhoeal sickness and its administration in the course of this decade. Oral rehydration strategy and zinc supplementation have proved to be extremely helpful in this aspect. Methods: A descriptive approach has been utilised to evaluate the knowledge of women in regards to the use of zinc supplementation with ORS in overseeing diarrhoea. Purposive sampling procedure was used to choose 100 mothers. The researcher assessed the knowledge of the study subjects regarding the advantages of zinc with ORS using a structured knowledge questionnaire. The gathered information was assessed by graphic and inferential measurements. Results: 63% of women got average score and 1% of women obtained very good score, 2% of women obtained poor score and not even a single woman got very poor score. The mean knowledge score of women regarding the benefits of zinc with ORS in managing diarrhoea was 17.24. Conclusion: Women are the greatest health workers who make all the possible efforts to provide their families with everything. If women possess the required knowledge, they themselves would leave no stone unturned to use the various preventive measures and get rid of diarrhoea for the health of their family members. So, the knowledge of women related to health services needs to be updated and improved.

Effect of Zinc on Testosterone Levels and Sexual Function of Postmenopausal Women: A Randomized Controlled Trial

This study aimed to investigate the effect of zinc supplementation on testosterone levels and sexual function in postmenopausal women. This randomized clinical trial was performed on 116 postmenopausal women with serum zinc levels below 62, and low sexual function who were randomly divided into two groups: intervention and control. Serum zinc levels, testosterone, hemoglobin and hematocrit, as well as their Female Sexual Function Index (FSFI) were evaluated before and after the intervention. Data analysis was performed using paired and independent t-tests, Fisher’s exact test, and Chi Square test. The use of zinc supplementation in the intervention group significantly improved sexual desire, arousal, orgasm, satisfaction, vaginal moisture, and pain during intercourse and also the overall score of sexual function compared to the control group (p < 0.001). Zinc supplementation in the intervention group, resulted in a significant increase in testosterone levels compared to the control group, which improved sexual function in postmenopausal women non-significantly. The results of this study showed that zinc supplementation can improve testosterone levels and sexual function in postmenopausal women. Using this supplement in postmenopausal women having zinc insufficiency is recommended. Also, there is need for more studies to prove the effect of zinc on testosterone and sexual function.

A Study to assess the Effectiveness of Information Booklet on Knowledge of Mothers regarding Use of Zinc Supplementation in Managing Diarrhoea among Under Five Children in a selected Rural Community in Bhopal

Background: Zinc supplementation is suggested in all intense bowel issues in kids from non-industrial nations. We planned to survey whether zinc supplementation would be similarly compelling against every one of the normal life forms related to intense looseness of the bowels. Method:A semi-exploratory one gathering, pre-test post-test configuration was utilised for the examination. Purposive testing procedure was used to choose 40 mothers. The specialist evaluated the information with respect to the advantages of zinc utilising organised information survey. On the seventh day, a post-test was conducted. The gathered information was examined using graphic and inferential measurements.Result: The mean post-test information score (20.33) was higher than the mean pre-test knowledge score (11.95). The mean contrast between post-test and pre-test knowledge score was profoundly huge. The obtained ‘t’ value (13.60) was higher than the table value. There was no significant relationship between knowledge score and chosen demographic variables like age, number of kids, occupation, family, income, religion with the exception of educational status of mothers.Interpretation and Conclusion: The post-test knowledge score being higher than the pre-test knowledge score leads to the conclusion that the information booklet is a very useful method of improving the information of the mothers regarding zinc supplementation in managing diarrhoea among under-five children.

Increased zinc and albumin but lowered copper in children with transfusion-dependent thalassemia

BackgroundMeasurements of copper and zinc in transfusion-dependent thalassemia (TDT) show contradictory results. Aim of the studyTo examine serum levels of these minerals in TDT in relation to iron overload indices and erythron variables. MethodsThis study recruited 60 children with TDT and 30 healthy controls aged 3–12 years old. ResultsZinc was significantly higher in TDT children than in controls, while copper and the copper to zinc ratio were significantly lowered in TDT. Serum zinc was significantly associated with the number of blood transfusions and iron overload variables (including serum iron and TS%) and negatively with erythron variables (including hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin). Serum copper was significantly and negatively associated with the same iron overload and erythron variables. The copper to zinc ratio was significantly correlated with iron, TS%, ferritin, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. Albumin levels were significantly higher in TDT children than in control children. ConclusionOur results suggest that the increase in zinc in children with TDT may be explained by iron loading anemia and hemolysis and the consequent shedding of high amounts of intracellular zinc into the plasma. Increased albumin levels and treatment with Desferral may further contribute towards higher zinc levels in TDT. We suggest that the elevations in zinc in TDT are a compensatory mechanism protecting against infection, inflammation, and oxidative stress. Previous proposals for prophylactic use of zinc supplements in TDT may not be warranted.

A study of serum zinc levels in febrile seizures

Febrile seizures are the most common cause of convulsions in children. However, the exact underlying etiology and the pathophysiological mechanisms are yet to be established. Various theories have been put forward regarding the role of trace elements as predisposing factors in causing the convulsions. Among them, Zinc is the most interesting trace element whose role in diarrhea and pneumonia is well proven. Serum Zinc levels has been long associated with the febrile seizures. The main reason is still unknown for febrile seizures. In this prospective study, we evaluated zinc level in children with the first FS attack. Our findings can help clinicians with a fair idea of serum zinc levels about the use of zinc supplements for preventing the recurrence of febrile seizures via regulation of some neurological functions.

A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8

BackgroundThe solute carrier family 30 member 8 gene (SLC30A8) encodes a zinc transporter in the pancreatic beta cells and the major C-allele of a missense variant (rs13266634; C/T; R325W) in SLC30A8 is associated with an increased risk of type 2 diabetes (T2D). We hypothesized that the association between zinc intake and T2D may be modified by the SLC30A8 genotype.ResultsWe carried out a prospective study among subjects with no history cardio-metabolic diseases in the Malmö Diet and Cancer Study cohort (N = 26,132, 38% men; 86% with genotype data). Zinc intake was assessed using a diet questionnaire and food record. During a median follow-up of 19 years, 3676 T2D cases occurred. A BMI-stratified Cox proportional hazards regression model with attained age as the time scale was used to model the association between total and dietary zinc intake, zinc supplement use, zinc to iron ratio, and risk of T2D adjusting for putative confounding factors.The median total zinc intake was 11.4 mg/day, and the median dietary zinc intake was 10.7 mg/day. Zinc supplement users (17%) had a median total zinc intake of 22.4 mg/day. Dietary zinc intake was associated with increased risk of T2D (Ptrend < 0.0001). In contrast, we observed a lower risk of T2D among zinc supplement users (HR = 0.79, 95% CI 0.70–0.89). The SLC30A8 CC genotype was associated with a higher risk of T2D (HR = 1.16, 95% CI 1.07–1.24), and the effect was stronger among subjects with higher BMI (Pinteraction = 0.007). We observed no significant modification of the zinc-T2D associations by SLC30A8 genotype. However, a three-way interaction between SLC30A8 genotype, BMI, and zinc to iron ratio was observed (Pinteraction = 0.007). A high zinc to iron ratio conferred a protective associated effect on T2D risk among obese subjects, and the effect was significantly more pronounced among T-allele carriers.ConclusionsZinc supplementation and a high zinc to iron intake ratio may lower the risk of T2D, but these associations could be modified by obesity and the SLC30A8 genotype. The findings implicate that when considering zinc supplementation for T2D prevention, both obesity status and SLC30A8 genotype may need to be accounted for.

From guidelines to local realities: evaluation of oral rehydration therapy and zinc supplementation in Guatemala

ABSTRACTObjective.Diarrhea remains a leading cause of morbidity and mortality for children in low- and middle-income countries throughout the Americas. The World Health Organization (WHO) has developed guidelines on incorporating zinc supplementation (ZS) with traditional oral rehydration therapy (ORT) in order to shorten the duration of diarrheal episodes and to reduce poor health outcomes. Guatemala adopted these guidelines in 2011, but they have not yet been fully implemented at the community level. The objectives of this study were: (1) to co-design an ORT/ZS training program for community members with local health promoters that is appropriate to the local context and (2) to understand how attitudes and behaviors of community members changed after receiving training from the study promoters.Methods.In an observational study, community health promoters in rural Guatemala were trained according to WHO guidelines, and they worked collaboratively with the study team to develop a training curriculum to implement in their community. Community-based surveys, interviews, and focus group discussions were used to assess acceptability, accessibility, and availability of oral rehydration therapy and zinc supplementation.Results.Use of ORT increased from 63% to 95% among community members following training by local health promoters. Satisfaction with the service offered by health promoters increased from 63% to 90% amongst community members trained by the study promoters. However, knowledge and use of zinc supplementation remained low, which was attributable to unavailability of zinc in the study community.Conclusions.Use of trained community health promoters is an effective way to translate WHO guidelines to local contexts and overcome sociocultural barriers to care. However, the health system’s structure must support availability of essential medicines in order to effectively implement those guidelines.

Blood cadmium concentrations and environmental exposure sources in newcomer South and East Asian women in the Greater Toronto Area, Canada

BackgroundImmigrant women are often identified as being particularly vulnerable to environmental exposures and health effects. The availability of biomonitoring data on newcomers is limited, thus, presenting a challenge to public health practitioners in the identification of priorities for intervention. ObjectivesIn fulfillment of data needs, the purpose of this study was to characterize blood concentrations of cadmium (Cd) among newcomer women of reproductive age (19–45 years of age) living in the Greater Toronto Area (GTA), Canada and to assess potential sources of environmental exposures. MethodsA community-based model, engaging peer researchers from the communities of interest, was used for recruitment and follow-up purposes. Blood samples were taken from a total of 211 newcomer women from South and East Asia, representing primary, regional origins of immigrants to the GTA, and environmental exposure sources were assessed via telephone survey. Metal concentrations were measured in blood samples (diluted with 0.5% (v/v) ammonium hydroxide and 0.1% (v/v) octylphenol ethoxylate) using a quadrupole ICP-MS. Survey questions addressed a wide range of environmental exposure sources, including dietary and smoking patterns and use of nutritional supplements, herbal products and cosmetics. ResultsA geometric mean (GM) blood Cd concentration of 0.39µg/L (SD:±2.07µg/L) was determined for study participants (min/max: <0.045µg/L (LOD)/2.36µg/L). Several variables including low educational attainment (Relative Ratio (RR) (adjusted)=1.50; 95% CI 1.17–1.91), milk consumption (RR (adjusted)=0.86; 95% CI 0.76–0.97), and use of zinc supplements (RR (adjusted)=0.76; 95% CI 0.64–0.95) were observed to be significantly associated with blood Cd concentrations in the adjusted regression model. The variable domains socioeconomic status (R2adj=0.11) and country of origin (R2adj=0.236) were the strongest predictors of blood Cd. ConclusionBlood Cd concentrations fell below those generally considered to be of human health concern. However, negative health effects cannot be entirely excluded, especially for those that fall in the upper percentile range of the distribution, given the mounting evidence for negative health outcomes at low environmental exposure concentrations.