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The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se ( 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%–36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients’ low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.

This study examined the status of oxidative stress in 599 couples undertaking in vitro fertilization (IVF) treatment and its association with reproductive hormones, smoking, and outcomes. Oxidative stress biomarkers such as malondialdehyde, 8-hydroxy-2-deoxyguanosine, hydrogen peroxide (H2O2), catalase (CAT), and total antioxidant capacity (TAC) were determined in follicular fluid and seminal plasma. Tail moment (TM) was used to evaluate DNA damage in the sperm and granulosa cells. Reproductive hormones in serum and cotinine (COT) in urine, follicular fluid, and seminal plasma samples were determined. Separate multivariate linear regression was used to assess associations between levels of each oxidative stress biomarker and each hormone and smoking parameter (modeled as natural log-transformed). The findings indicate that some oxidative stress and DNA damage biomarkers played a role in disrupting certain reproductive hormones in women and their male partners either by overproducing reactive oxygen species or reducing antioxidant defense capacity. Although women were nonsmokers, COT levels > 50 and 10 µg/L in urine and follicular were observed in 5.7 and 1.7%, respectively. Levels of follicular fluid COT were positively associated with H2O2 and TM. We used log-binomial multivariate regression to estimate relative risks for the association between oxidative stress/DNA damage and IVF binary outcomes (fertilization rate > 50%, biochemical pregnancy, clinical pregnancy, and live birth). An increase in the CAT levels of follicular fluid was associated with a 48 and 41% decrease in the risk of poor fertilization rate (≤50%) and unsuccessful live birth, respectively. After the models were adjusted for hormonal factors, the associations remained the same, except that the elevated TAC in follicular fluid became significantly associated with a decrease of 42% in the risk of poor fertilization rate (≤50%). The higher antioxidant activity (CAT and TAC) in follicular fluid might positively impact specific IVF outcomes. Lay summary Oxidative stress occurs when antioxidant molecules are insufficient in the body to destroy free radicals that can damage the cells, proteins and DNA, causing different health conditions, including infertility. The role of oxidative stress in female infertility has not received as much attention as male infertility, and research is still limited. This study explored whether the overproduction of free radicals can impact the success of in vitro fertilization (IVF) treatment using several biological markers such as hydrogen peroxide, catalase, and total antioxidant capacity. Our findings revealed that the high antioxidant levels in the fluid surrounding the egg were linked with a high fertilization rate. Additionally, oxidative stress status in couples was associated negatively with several reproductive hormones and smoking status. Biomarkers of oxidative stress and DNA damage might have potential applications in evaluating IVF patients’ clinical characteristics such as causes of infertility, hormonal profile, fertilization rate, implantation and live birth.

This prospective study of 599 couples seeking fertility treatment and who were recruited between 2015 and 2017 was conducted to (a) explore the associations between phthalate exposure and in vitro fertilization (IVF) outcomes; and (b) examine the implication of oxidative stress as a mediator of these. We measured eight phthalate metabolites in two spot urine samples; oxidative stress biomarkers such as malondialdehyde, 8-hydroxy-2-deoxyguanosine, hydrogen peroxide, catalase (CAT), and total antioxidant capacity in follicular fluid and seminal plasma. We also examined DNA damage in sperm and granulosa cells. Couples were exposed to a broad range of phthalate compounds and seven metabolites were detected in over 94% of the urine samples, whereas monobenzyl phthalate was found in only 24% of women and 26% of men. Our results showed high levels of seven urinary phthalate metabolites (except monobenzyl phthalate) and a notable increase in many oxidative stress markers in both follicular fluid and seminal plasma. However, their associations with exposure were rather limited. Multivariate binomial regression modeling showed higher levels of follicular CAT levels reduced the probability of fertilization rate (≤ 50%) [Adjusted relative risk (RRadj) = 0.52, p = 0.005] and unsuccessful live birth (RRadj = 0.592, p = 0.023). We observed a 46% decrease in the probability of clinical pregnancy in association with an elevated percentage of DNA in the tail (RRadj = 0.536, p = 0.04). There was a 32% and 22% increase in the probability of clinical pregnancy and unsuccessful live birth associated with higher levels of mono-(2-ethylhexyl) phthalate (RRadj = 1.32, p = 0.049) and monoethyl phthalate (RRadj = 1.22, p = 0.032) in women, respectively. In contrast, the probability of clinical pregnancy reduced by 20% with higher levels of mono-(2-ethyl-5-carboxypentyl) phthalate (RRadj = 0.797, p = 0.037) and 19.6% with mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (RRadj = 0.804, p = 0.041) in men. Other oxidative stress biomarkers or urinary phthalate metabolites showed suggestive relationships with certain IVF outcomes. Lastly, our results demonstrated that elevated levels of CAT in follicular fluid might have a positive impact on fertilization rate ≥ 50% and successful live birth. CAT seems to play a potential role in mediating the relationship between the risk of poor fertilization rate and MEOHP and mono-isobutyl phthalate. Additional data are required to understand the clinical implications of oxidative stress and its contribution to the reproductive toxicity of phthalate exposure.

We previously measured the levels of inorganic mercury, methylmercury, lead, cadmium, and manganese in the breast milk of 203 healthy Saudi mothers who participated in a cross-sectional study between 2011 and 2013. The current study aimed to (1) calculate reference values (RVs) for these metals in breast milk based on the 95th percentile of the metal and the corresponding 95% confidence interval following the approach of the German Human Biomonitoring Commission, and (2) assess the health risk associated with these metals (except lead) by determining the hazard quotient (HQ) and hazard index (HI) for breastfed infants. The risk characterization for the lead was applied using the margin of exposure (MOE) approach. Moreover, the cancer risk (CR) associated with lead was calculated. The RV95s (percentage of samples for which the value was higher than the set value) for inorganic mercury, methylmercury, total mercury, cadmium, lead, and manganese in breast milk (μg/L) were 1.5 (7.9%), 1.5 (5.4%), 2.8 (8.9%), 2.5 (8.4%), 53 (11.3%), and 22.3 (11.8%) μg/L, respectively. The methylmercury, lead, and manganese levels in the present study were higher than those reported previously. The HQ for methylmercury greater than 1 was found in 68.5% of the samples, indicating there may be a potential non-carcinogenic health risk of infant exposure to the toxic metal via breast milk consumption. Despite the high cadmium and manganese levels in breast milk, our results suggested no health risk (HQ 1, with methylmercury (74%) being the major contributor. The estimated MOE mean value of 0.134, less than 1, indicates that our breastfed infants may be at increased risk of neurodevelopmental impairments. The CR for lead in two infants was higher than the acceptable level of 1 × 10−4. Although our results may suggest potential carcinogenic and non-carcinogenic risks of infant exposure to toxic metals through breast milk consumption, the benefits of breastfeeding are well recognized and outweigh the potential risks.

Certain endocrine disruptor chemicals are involved in the pathogenesis of polycystic ovary syndrome (PCOS), a hormonal disease related to infertility in women. Phthalates are the most common plasticizers found in several consumer products. Experimental and epidemiologic evidence suggests that some phthalates disrupt endocrine functions in reproductive mechanisms and development. We previously measured the levels of eight phthalate metabolites in the urine of 599 Saudi women who underwent in vitro fertilization (IVF) treatment and were enrolled in a prospective study (2015–2017). The current nested case-control study aimed to determine the association between urinary levels of phthalate metabolites and PCOS. Overall, 441 women from the IVF study were identified as eligible for this study. Women in the case group included those diagnosed with PCOS (N = 82). The control group comprised those unable to conceive due to male azoospermia or who underwent preimplantation genetic diagnosis (N = 359). Most urinary phthalate metabolite levels were several-fold higher than those reported in national surveys from other countries. The ratio of luteinizing hormone to follicle-stimulating hormone, an index of PCOS, was significantly higher in the case than in the control group, with no indication of its association with phthalate metabolites. The logistic regression model was applied after adjusting for confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each metabolite modeled as a natural logarithm (ln). For each ln-unit increase in the sum of the four di (2-ethylhexyl) phthalate (∑4DEHP) metabolites as well as two individual metabolites, mono-(2-ethyl-5-oxohexyl) phthalate and mono-(2-ethyl-5-carboxypentyl) phthalate, the odds of PCOS increased by 40.5% [OR = 1.405 (95% CI: 1.025, 1.925)], 41.1% [OR = 1.055 (95% CI: 1.055, 1.885)], and 38.6% [OR = 1.386 (95% CI: 1.033, 1.86)], respectively. In contrast, the % odds of PCOS decreased marginally significantly by 44% [OR = 0.560 (95% CI: 0.313, 1.002)] with an ln-unit increase of %MEHP4, the ratio of mono-(2-ethylhexyl) phthalate to ∑4DEHP. These findings suggest that DEHP may contribute to PCOS, and further investigation is required to understand the underlying mechanisms.

Exposure to heavy metals can cause renal injury, which has been well documented in occupational exposure. Studies of low exposure in the general population, however, are still scarce, particularly for vulnerable populations such as mothers and young children. This study evaluated exposure to heavy metals, and biomarkers of renal function and oxidative stress in 944 lactating mothers and their infants and investigated the role of the interaction between heavy metals and oxidative stress in altering renal function. Mother and infant urine samples were analyzed to measure mercury (Hg), cadmium (Cd), and lead (Pb) concentrations for determining body-burden exposure; N-acetyl-β-d-glucosaminidase (NAG), α1-microglobulin (α1-MG), albumin (ALB), and creatinine (Cr) concentrations for determining early renal injury; and 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) concentrations for determining oxidative stress. The median concentrclearlyations in mothers presented as μg/g Cr (infants as μg/l) for Hg, Cd, and Pb were 0.695 (0.716), 0.322 (0.343), and 3.97 (5.306) respectively. The mothers and their infants had clearly been exposed to heavy metals and had levels higher than the reference values reported for the general populations of USA, Germany, and Canada. Multiple regression analyses clearly demonstrated associations between urinary heavy metals in quartiles and several renal and oxidative biomarkers in mothers and to a lesser extent their infants. s coefficients for urinary excretions of MDA, 8-OHdG, ALB, α1-MG, NAG, and Cr in mothers were high in the highest quartile of Hg (1.183-51.29μg/g Cr or 1.732-106.95μg/l), Cd (0.565-765.776μg/g Cr or 0.785-1347.0μg/l), and Pb (6.606-83.937μg/g Cr or 9.459-80.826μg/l), except Pb was not associated with ALB. Infants in the highest Pb quartile (9.293-263.098μg/l) had the highest s coefficients of urinary excretion of MDA, 8-OHdG, ALB, NAG, and Cr. Significant increasing trend in biomarkers across the quartiles of the three metals was seen in both mothers and infants (ptrend

We previously reported high levels of phthalate esters (PAEs) added as solvents or fixatives in 47 brands of perfumes. Diethyl phthalate was the most abundant compound (0.232–23,649 ppm), and 83.3% of the perfumes had levels >1 ppm, the threshold limit cited by a Greenpeace investigation. All samples had dimethyl phthalate levels higher than its threshold limit of 0.1 ppm, and 88, 38, and 7% of the perfumes had benzyl butyl phthalate, di(2-ethylhexyl) phthalate, and dibutyl phthalate levels, respectively, above their threshold limits. The role of PAEs as endocrine disruptors has been well documented, but their effect on genotoxic behavior has received little attention. We used in vitro single-cell gel electrophoresis (comet) and micronucleus (MN) assays with human lymphoblastoid TK6 cells to evaluate the genotoxic potency of 42 of the same perfumes and to determine its association with PAEs. All perfumes induced more DNA damage than a negative control (NEG), ≥ 90% of the samples caused more damage than cells treated with the vehicles possibly used in perfume’s preparations such as methanol (ME) and ethanol (ET), and 11.6% of the perfumes caused more DNA damage than a positive control (hydrogen peroxide). Chromosome breakage expressed as MN frequency was higher in cells treated with 71.4, 64.3, 57.1, and 4.8% of the perfumes than in NEG, cells treated with ME or ET, and another positive control (x-rays), respectively. The genotoxic responses in the comet and MN assays were not correlated. The comet assay indicated that the damage in TK6 cells treated with five PAEs at concentrations of 0.05 and 0.2 ppm either individually or as a mixture did not differ significantly from the damage in cells treated with the perfumes. Unlike the comet assay, the sensitivity of the MN assay to PAEs was weak at both low and high concentrations, and MN frequencies were generally low. This study demonstrates for the first time the possible contribution of PAEs in perfumes to DNA damage and suggests that their use as solvents or fixatives should be regulated. Other ingredients with mutagenic/genotoxic properties, however, may also have contributed to the DNA damage. Future studies should focus on applying a series of assays that use different cellular models with various endpoints to identify the spectrum of genotoxic mechanisms involved.

Plasticizers such as phthalate esters (PAEs) and bisphenol A (BPA) are highly persistent organic pollutants that tend to bio-accumulate in humans through the soil-plant-animal food chain. Some studies have reported the potential carcinogenic and teratogenic effects in addition to their estrogenic activities. Water resources are scarce in Saudi Arabia, and several wastewater treatment plants (WTPs) have been constructed for agricultural and industrial use. This study was designed to: (1) measure the concentrations of BPA and six PAEs, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP) and dioctyl phthalate (DOP), in secondary- and tertiary-treated wastewater collected from five WTPs in three Saudi cities for four to five weeks and (2) test their potential genotoxicity. Three genotoxicological parameters were used: % tail DNA (%T), tail moment (TM) and percentage micronuclei (%MN). Both DBP and DEHP were detected in all treated wastewater samples. DMP, DEP, BBP, DOP, and BPA were found in 83.3, 84.2, 79, 73.7 and 97.4% of the samples, respectively. The levels of DMP (p

Phthalates are chemicals used as plasticizers and solvents in many consumer products but are suspected of disrupting the endocrine system and are known for their reproductive/developmental health risks. This study examined the extent and predictors of phthalate exposure among 599 couples undergoing in vitro fertilization. A questionnaire was administered to obtain sociodemographic, health, and lifestyle data, and two spot urine samples were collected from the couples to analyze eight phthalate metabolites, cotinine (COT) as a smoking index, and creatinine to adjust for urine dilution. Seven phthalate metabolites were detected in > 94% of the urine samples, and monobenzyl phthalate (MBzP) was found in 24% of the women and 26% of their male partners. Median phthalate levels were highest for monoethyl phthalate (MEP), at 333.26 μg/l in women and 290 μg/l in male partners, and lowest for MBzP, at 1.17 μg/l in women and 1.14 μg/l in male partners. Correlation coefficients of ≥ 0.4 between the women and their male partners for the eight urinary phthalate metabolites may indicate a shared source of exposure. A multivariate regression model was used to assess the association between predictors and each urinary phthalate metabolite. Several potential predictors for the variations in specific urinary phthalate metabolites were identified, including the body mass index, age, socioeconomic status, and regional distribution for both women and their male partners but with slightly different patterns. Women with a history of breastfeeding, using bottled water for cooking and storing food in plastic bags had lower MEP (8.7%), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (9.2%), and both mono-iso-butyl phthalate and MECPP (8.2 and 8.1%). A history of contraceptive use was associated with an increase in MECPP (8.7%), mono-(2-ethyl-5-hydroxyhexyl) phthalate (11.4%), mono-(2-ethyl-5-oxohexyl) phthalate (7.6%), and the molar sum of bis (2-ethylhexyl) phthalate metabolites (8.9%). Urinary COT levels were associated with an increase of 10–16% in all urinary metabolites in women but of only 10.5% in mono-(2-ethylhexyl) phthalate in male partners. More than 95% of the couples reported the use of cosmetics, perfumes, and personal-care products, but we were not able to find associations with urinary phthalate metabolites, perhaps due to their short half-lives. MEP levels associated with the use of household cleaning products were 11.2% higher in male partners. Our levels were generally higher than those reported elsewhere, perhaps due to different lifestyles, cultural practices, dietary habits, use of personal-care products, and governmental legislation.

A total of 206 lactating mothers and their infants (3-12 months) were included in this study to evaluate postnatal exposure to neurotoxic pollutants such as methylmercury (MeHg), lead (Pb), manganese (Mn), dichlorodiphenyltrichloroethane (DDT) and its metabolites [dichlorodiphenyldichloroethane (DDD), and dichlorodiphenyldichloroethylene (DDE)] and their association with delayed neurological development and to explore the protective role of selenium (Se) against chemical neurotoxicity. Neurodevelopmental performance was evaluated using Denver Developmental Screening Test II and Parents' Evaluation of Developmental Status (PEDS). Multivariate log-binomial regression modeling was applied for both single and multiple exposures to chemicals using a principal component analysis that generated six principal components. Both mothers and their infants had been exposed to metals and DDT metabolites, with some exceeding the accepted permissible limits. The geometric means of MeHg, Pb, Mn, DDD, DDE and DDT levels in breast milk were 1.333, 45.327, 15.576, 0.069, 0.542 and 1.08 μg/l, respectively. A single-exposure model identified a high risk of reduced PEDS performance significantly associated with DDD in breast milk [relative risk (RR) = 1.484; 95% confidence interval (95%CI) = 1.091-2.019] and marginally significantly associated with Pb in the mothers' blood (RR = 2.164; 95%CI = 0.87-5.382). We did not find a protective role of Se in neurodevelopment due to its high levels in the mothers. Models of multi-chemical exposure indicated that Mn in blood and breast milk, Se in blood and Pb in the mothers' urine were marginally significantly associated with a high risk of reduced PEDS performance (RR = 0.424; 95%CI = 0.176-1.022). The use of multi-chemical exposure approach in early life risk assessments is important because it indicates real-world exposure. Our results were not conclusive because the sample size was small, so future studies examining the implications to health of the impact of prenatal/postnatal exposure to a mixture of chemicals in the Saudi population are merited.

Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in humans, because phthalates can interfere with endocrine function. We collected spot urine samples from 291 pregnant women in their first trimester (9.8 ± 2.3 gestational weeks) recruited in an ongoing prospective cohort study in Saudi Arabia. A second urine sample was collected within 1–7 d after enrollment. The aims of this study were to: (1) assess the extent of exposure to phthalates during the first trimester and (2) estimate the risk from single and cumulative exposures to phthalates. Most phthalate metabolites' urinary levels were high, several-fold higher than those reported in relevant studies from other countries. The highest median levels of monoethyl phthalate, mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and mono-(2-ethylhexyl) phthalate (MEHP) in μg/l (μg/g creatinine) were 245.62 (197.23), 114.26 (99.45), 39.59 (34.02), and 23.51 (19.92), respectively. The MEHP levels were highest among three di (2-ethylhexyl) phthalate (DEHP) metabolites. %MEHP4, the ratio of MEHP to four di (2-ethylhexyl) phthalate metabolites (∑4DEHP), was 44%, indicating interindividual differences in metabolism and excretion. The hazard quotient (HQ) of individual phthalates estimated based on the reference dose (RfD) of the U.S. Environmental Protection Agency indicated that 58% (volume-based) and 37% (creatinine-based) of the women were at risk of exposure to ∑4DEHP (HQ > 1). Based on the tolerable daily intake (TDI) from the European Food Safety Authority, 35/12% (volume-/creatinine-based data) of the women were at risk of exposure to two dibutyl phthalate (∑DBP) metabolites (MiBP and MnBP). The cumulative risk was assessed using the hazard index (HI), the sum of HQs of all phthalates. The percentages of women (volume-/creatinine-based data) at health risks with an HI > 1 were 64/40% and 42/22% based on RfD and TDI, respectively. In view of these indices for assessing risk, our results for the anti-androgenic effects of exposing pregnant women to ∑4DEHP and ∑DBP early during pregnancy are alarming.

Many studies have highlighted the widespread use of skin-lightening creams containing mercury by women during and after pregnancy to remove dark spots. Women, especially pregnant and lactating mothers using these products are at risk of mercury poisoning because sometimes it has no clinical symptoms, particularly during early exposure. Studies have shown that prenatal and postnatal mercury exposure can cause permanent neurological damage in children. Furthermore, mercury can cause women infertility and birth defects. Even though several studies have examined the reproductive and/or developmental consequences of gestational and lactational mercury exposure from fish consumption and/or dental amalgam, no studies have assessed the possible effects of the long-term use of mercury-containing skin-lightening products by women of childbearing age on their pregnancy outcome and children's health. This commentary aims to collate information on the popular use of mercury-containing skin-lightening creams and sheds the light to the readers about the limitations of the available data on its impact during a prenatal and/or postnatal period. There is an urgent need to assess the adverse health effects of applying these products during pregnancy or lactation on child growth and development through birth cohort studies. Until data from these studies are available, women should be advised not to use topical skin-lightening creams during pregnancy and lactation.

This cross-sectional study analyzed mercury (Hg) levels in healthy Saudi mothers and their infants (age 3-12 months) and examined the influence of Hg on the infants' neurodevelopment using screening tools, such as the Denver Developmental Screening Test II (DDST-II) and Parents' Evaluation of Developmental Status (PEDS). A total of 944 mothers and their 944 infants were recruited from 57 Primary Health Care Centers (PHCCs) in Riyadh. The total Hg (THg) levels were measured in the mothers' and infants' urine (UTHg-M and UTHg-I) and hair (HTHg-M and HTHg-I) samples and in the breast milk and mothers' blood. Methylmercury (MeHg) levels were determined in hair samples from the mothers (MeHg-M) and infants (MeHg-I). Only 40.1% of the infants were breast-fed when enrolled, and 59.9% had stopped breastfeeding. Only 1.8% of the mothers and 0.3% of the infants had MeHg levels above the Environmental Proection Agency (EPA) reference dose (1 μg/g), with low medians of 0.132 and 0.091 μg/g dw, respectively, but the MeHg levels were significantly associated with infant DDST-II performance. The levels of corrected UTHg-M for creatinine (Cr), HTHg-M, HTHg-I, and HMeHg-M, however, displayed an association with infant PEDS performance. The medians and percentage of the tested population that exceeded the recommended limits for Hg in urine and hair set by the World Health Organization (5 μg/g Cr) and EPA (1 μg/g) were 0.695 μg/g Cr and 3% UTHg, 0.118 μg/g dw and 4.1% HTHg-M, 0.101 μg/g dw and 2.8% HTHg-I, and 0.132 μg/g dw and 1.8% HMeHg-M. Our study provides evidence of an association between some Hg measures and delays in infant neurodevelopment, despite their low levels and regardless of the infant's breastfeeding status. The results are of potential concern, because delayed psychomotor or mental performance in infants could be an indicator of later neurocognitive development in children, which may persist into adulthood, as shown in other studies. The absence of local standardization of the DDST-II and PEDS screening tools might raise some questions, although the DDST-II has been used in local institutions for a number of years. The development of effective standardized developmental screening tools is necessary to ensure that all children at risk of neurodevelopmental problems early in life are identified so that they can receive appropriate and timely intervention.

In this study, we determined DNA damage and chromosome breakage (indicators of genotoxicity) and cell viability (an indicator of cytotoxicity) in human lymphoblastoid TK6 and Chinese hamster ovary (CHO) cells treated with 33 e-liquids using in vitro single cell gel (comet), micronucleus (MN), and trypan blue assays, respectively. We also measured the contents of nicotine, five phthalate esters, and DL-menthol in the e-liquids to examine their effects on DNA damage, chromosome breakage, and cell viability. Our chemical analyses showed that: (1) six e-liquids had nicotine ≥2-fold higher than the manufacture’s label claim (2–3.5 mg); (2) both dimethyl- and dibutyl-phthalate levels were >0.1 μg/g, i.e., their threshold limits as additives in cosmetics; and (3) the DL-menthol contents ranged from 0.0003 to 85757.2 μg/g, with those of two e-liquids being >1 mg/g, the threshold limit for trigging sensory irritation. Though all the e-liquids induced DNA damage in TK6 cells, 20 resulted in cell viabilities ≤75%, indicating cytotoxicity, yet the inverse relationship between cell viability and DNA damage (r = −0.628, p = 0.003) might reflect their role as pro-apoptotic and DNA damage inducers. Fifteen e-liquids induced MN% in TK6 cells ≥3-fold that of untreated cells. Some of the increase in %MN might be false due to high cytotoxicity, yet six brands showed acceptable cell viabilities (59–71%), indicating chromosome damage. DNA damage and %MN increased when the TK6 cells were exposed to metabolic activation. The CHO cells were less sensitive to the genotoxic effects of the e-liquids than the TK6 cells. DL-menthol was found to be associated with decreased cell viability and increased DNA damage, even at low levels. We cannot dismiss the presence of other ingredients in e-liquids with cytotoxic/genotoxic properties since out of the 63 different flavors, 47 induced DNA damage (≥3-folds), and 26 reduced cell viability (≤75%) in TK6 cells.

We previously assessed the exposure of Saudi women to mercury, cadmium and lead based on reference values (RVs) established for other populations experiencing differences in environmental exposure, diet and lifestyle as an indicator of background exposure to pollutants. The present study aimed to (1) calculate RV95 for mercury, cadmium and lead in blood and urine from Saudi women based on the 95th percentile of the metal and its corresponding 95% confidence interval (95%CI) as defined by the German Human Biomonitoring Commission, and (2) compare with RV95s established in other countries. RV95s were derived using data from two different human biomonitoring studies measured three metals in the blood (2005-2006), and both urine and blood (2011-2013) from healthy non-smokers and non-occupationally exposed women living in Al-Kharj and Riyadh. RV95s for mercury, cadmium and lead in Al-Kharj (Riyadh) blood were 5.9 (1.6) μg/l, 1.4 (1.9) μg/l and 4.3 (4.8) μg/dl, respectively. RV95s for urinary mercury, cadmium and lead in Riyadh samples expressed in μg/l (μg/g creatinine) were 2.5 (1.9), 1.2 (0.96) and 14 (10.8), respectively. Values in both matrices remained high even when potential factors such as secondhand smoking, dental amalgam, and/or fish consumption excluded. RV95s for metals in blood were generally higher than in other countries, except for mercury in Riyadh samples, which was also 4-fold lower than in Al-Kharj. However, due to the time lag between the two studies, and since the Al-Kharj study was conducted 13 years ago, the most recent RV95s derived from the Riyadh study are recommended for Saudi women living in the Central region. The RV95s for urinary mercury and cadmium were comparable to other countries, but lead requires closer attention. To our knowledge, this study is the first to propose RV95s for mercury, cadmium, and lead in blood and urine of Saudi women of childbearing age, a population that is highly susceptible to the adverse health effects of these metals.

This prospective study examined the associations between the levels of eight urinary phthalate metabolites in 599 couples and in vitro fertilization (IVF) outcomes. We used log-binomial multivariate regression to estimate relative risks (RR) for the association between phthalate concentration and IVF binary outcomes (fertilization rate >50%, biochemical pregnancy, clinical pregnancy and live birth) for each woman after adjusting the model for the concentration in a male partner and each relevant confounders. RR was expressed per unit increase in log-transformed urinary metabolite concentration. The percentage of bis-2-ethylhexyl phthalate (DEHP) metabolites excreted as mono-2-ethylhexyl phthalate (MEHP) was calculated as %MEHP. Urinary MEHP in women was associated with an increased risk of biochemical pregnancy (RR = 1.35; p = 0.04), failed clinical pregnancy (RR = 1.56; p = 0.006) and live birth (RR = 1.54; p = 0.011). An increase in monoethyl phthalate was associated with a high risk of failed clinical pregnancy (RR = 1.25; p = 0.03) and live birth (RR = 1.35; p = 0.006). An increase in %MEHP was associated with an increase in the risk of biochemical pregnancy (RR = 1.55; p = 0.05), failed clinical pregnancy (RR = 1.73; p = 0.02) and live birth (RR = 1.65; p = 0.046). Our results demonstrated that exposure to some phthalates may adversely affect IVF outcomes, particularly when couples' exposure was jointly modeled, emphasizing the importance of a couple-based approach in assessing fertility outcomes. The associations between IVF outcomes and DEHP metabolites were stronger in women whose %MEHP was >75th percentile which may be due to their less efficient metabolism and excretion of DEHP and/or MEHP.

Evidence from previous studies has shown that phthalates may play a role in male reproductive function; however, results are still inconclusive, and the mechanism remains unclear. In this study, we first assessed whether exposure to phthalates is associated with altered reproductive hormones and semen parameters in 599 men attending an in vitro fertilization clinic. Secondly, we evaluated whether reproductive hormones could play a mediating role in the association between phthalates and sperm parameters. Eight phthalate metabolites were measured in two different spot urine samples: mono‑n‑butyl phthalate, mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate, and four oxidative metabolites of di‑(2‑ethylhexyl) phthalate (DEHP) [i.e., mono‑(2‑ethylhexyl) phthalate (MEHP), mono‑(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP), mono‑(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP), and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP)]. Semen parameters (concentration, volume, motility, and morphology) and reproductive hormones, i.e., follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone, estradiol (E2), testosterone (TEST) and prolactin (PROL) were also determined and considered the main study outcomes. Separate multivariate linear regression was used to assess associations between levels of each urinary phthalate metabolite, molar sum of DEHP metabolites (∑DEHP), percentage of MEHP to ∑DEHP (%MEHP), and each outcome (natural log-transformed). Inverse associations were observed between TEST and MiBP (β = −0.099), FSH and MEHHP (β = −0.087), and PROL and MEOHP (β = −0.102), while a positive relationship was seen between E2 and MEP (β = 0.098). %MEHP was associated positively with FSH (β = 0.118) and LH (β = 0.099), but negatively with TEST/LH (β = −0.086) and TEST/E2 (β = −0.109). Sperm concentration was associated positively with MECPP (β = 0.131), MEHHP (β = 0.117), MEOHP (β = 0.107) and ∑DEHP (β = 0.111), but negatively with %MEHP (β = −0.135). All p-values were

In the last few years, the use of phthalates in perfumes has gained attention because these chemicals are sometimes added intentionally as a solvent and a fixative. Five phthalate esters, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diethyl hexyl phthalate (DEHP), were measured in 47 branded perfumes using headspace solid phase microextraction (SPME) followed by gas chromatography-mass spectrometry (GC-MS). The results revealed considerable amounts of phthalate in all 47 brands with detection frequencies > limit of quantitation in the following order: DEP (47/47) > DMP (47/47) > BBP (47/47) > DEHP (46/47) > DBP (23/45). Of the 47 brands, 68.1, 72.3, 85.1, 36.2, and 6.7 % had DEP, DMP, BBP, DEHP, and DBP levels, respectively, above their reported threshold limits. Of these phthalates, DEP was found to have the highest mean value (1621.625 ppm) and a maximum of 23,649.247 ppm. The use of DEP in the perfume industry is not restricted because it does not pose any known health risks for humans. DMP had the second highest level detected in the perfumes, with a mean value of 30.202 ppm and a maximum of 405.235 ppm. Although DMP may have some uses in cosmetics, it is not as commonly used as DEP, and again, there are no restrictions on its use. The levels of BBP were also high, with a mean value of 8.446 ppm and a maximum of 186.770 ppm. Although the EU banned the use of BBP in cosmetics, 27 of the tested perfumes had BBP levels above the threshold limit of 0.1 ppm. The mean value of DEHP found in this study was 5.962 ppm, and a maximum was 147.536 ppm. In spite of its prohibition by the EU, 7/28 perfumes manufactured in European countries had DEHP levels above the threshold limit of 1 ppm. The DBP levels were generally low, with a mean value of 0.0305 ppm and a maximum value of 0.594 ppm. The EU banned the use of DBP in cosmetics; however, we found three brands that were above the threshold limit of 0.1 ppm, and all were manufactured in European countries. The results of this study are alarming and definitely need to be brought to the attention of the public and health regulators. Although some phthalate compounds are still used in cosmetics, many scientists and environmental activists have argued that phthalates are endocrine-disrupting chemicals that have not been yet proven to be safe for any use, including cosmetics. Phthalates may also have different degrees of estrogenic modes of action. Furthermore, we should not dismiss the widespread use of phthalates in everyday products and exposure to these chemicals from sources such as food, medications, and other personal care products.

The levels of heavy metals (lead, cadmium, methylmercury and arsenic) were determined in 37 brands of imported rice commonly consumed in Saudi Arabia after soaking and rinsing with water, and their potential health risks to residents were estimated by three indices: hazard quotient (HQ), hazard index (HI) and cancer risk (CR). The mean levels of lead, cadmium, methylmercury and total arsenic in soaked (rinsed) rice grains were 0.034 (0.057), 0.015 (0.027), 0.004 (0.007) and 0.202 (0.183) μg/g dry weight, respectively. Soaking or rinsing rice grains with water decreased lead and cadmium levels in all brands to safe levels. All brands had total arsenic above the acceptable regulatory limits, irrespective of soaking or rinsing, and eight soaked and 12 rinsed brands contained methylmercury. The levels of all heavy metals except cadmium were above the acceptable regulatory limits when the rice was neither rinsed nor soaked. Weekly intakes of lead, cadmium, methylmercury and total arsenic from soaked (rinsed) grains were 0.638 (1.068), 0.279 (0.503), 0.271 (0.309) and 3.769 (3.407) μg/kg body weight (bw). The weekly intakes of lead and methylmercury from the consumption of one rinsed and two soaked rice brands respectively, exceeded the Provisional Tolerance Weekly Intake set by the Food and Agriculture Organization and the World Health Organization. The weekly intake of total arsenic for all brands was above the lowest benchmark dose lower confidence limit (BMDL01) level of 0.3μg/kg bw/d for an increased cancer risk set by European Food Safety Authority. Either soaking or rinsing grains before consumption can minimize the non-carcinogenic health risks to residents from cadmium and lead (HQ 1 all brands) and to a lesser extent with methylmercury (HQ>1 in 4 brands), even when soaked or rinsed with water before consumption. The combined non-carcinogenic effect of all metals expressed as HI was >1, including soaked or rinsed rice, with total arsenic the major contributor followed by methylmercury. CR for total arsenic, whether consuming soaked, rinsed, un-soaked or unrinsed grains, exceeded the acceptable level of 10-4. Long-term consumption of rice contaminated with heavy metals, particularly arsenic, can pose potential health risks to the local population, especially vulnerable groups (pregnant women, children, elderly and patients). More attention should thus be given to contaminated rice and preventive measures should be taken.

Fruit juices are popular beverages regularly consumed by both adults and children. Various brands of different fruit juices in Saudi markets are packaged in disposable plastic bottles made of polyethylene terephthalate (PET). Some evidence suggests that phthalates may leach from PET bottles. Few studies have analyzed the presence or assessed the risk of phthalates in fruit juice. The concentrations of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), diethyl hexyl phthalate (DEHP), and di-n-octylphthalate (DOP) were measured in seven brands of commercially manufactured apple juice available in the Saudi market using solid-phase microextraction connected to gas chromatography-mass spectrometry. Nearly all targeted compounds were found in the brands of juice, with DOP being detected in all samples. Of 70 samples of apple juice, 11, 39, 2, 11 and 11 had levels of DEP, DBP, BBP, DEHP, and DOP, respectively, above their limit of quantification (LOQ). These phthalates may have either leached into the juice from the PET bottles or were contaminants during manufacturing. Benzyl benzoate (BB) was used as an internal standard, and was unexpectedly found in two brands of apple juice, which forced us to use external calibration method for quantifying the phthalates and to measure BB concentrations in these two brands. All samples were above the LOQ of 0.628 µg/L. BB exposure via the consumption of apple juice may represent a negligible risk, but the use of BB in cosmetics, personal-care products, and as a preservative in food demands studies to assess its potential impact on health. With the absence of regulations governing the safety of contaminants in these products, the presence of phthalates in apple juice or other dietary sources could pose a health risk to consumers.

This study was conducted to: (a) investigate the antagonistic interaction between selenium (Se) and mercury (Hg) in mothers and their newborns, (b) delineate the role of oxidative mechanisms induced by Hg exposure and (c) examine the protective effect of Se on Hg-induced oxidative stress and birth outcomes. Levels of Hg and Se were measured in umbilical cord blood and the placentas of 250 healthy mothers who participated in a study between 2006 and 2006 assessing prenatal exposure various pollutants. Levels of malondialdehyde (MDA) in cord and maternal blood and of 8-hydroxy-2-deoxyguanosine in urine were measured for assessing oxidative stress. Tail moment (TM) in the comet assay, as a biomarker of DNA damage was measured in samples of cord and maternal blood. The mean Se levels in umbilical cord blood (67.618±12.897μg/l) were lower than those reported in many countries, but none of the newborns had Se levels

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that are known to induce oxidative stress. There have been several reports about the link between PAH exposure and complications in pregnancy. This cross-sectional study was conducted to: (1) measure the levels of benzo(a)anthracene (BaA), chrysene (Ch), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), and dibenzo(a,h)anthracene (DBahA) in placentas and maternal and -umbilical cord blood obtained at delivery from 1578 women between June 2005 and 2006 in the area of Al-Kharj, Saudi Arabia; (2) assess their influence on various anthropometric measures of birth outcome taking into consideration the carcinogenic properties of these PAHs; and (3) determine the degree of PAH-related oxidative DNA damage and birth outcome. Among the five tested PAHs, only BaP was carcinogenic; therefore, the levels of the other four probable or possible carcinogenic PAHs (BaA, Ch, BaF, and DBahA) were summed as ∑4-PAHs. Levels of 1-hydroxypyrene (1-HP) were determined in maternal urine samples as a biomarker of PAH internal dose. Urinary cotinine (COT) was measured as an index of smoking. The following markers of oxidative stress were selected: malondialdehyde (MDA) in cord (C-MDA) and maternal (M-MDA) serum and 8-hydroxy-2-deoxyguanosine (8-OHdG) in maternal urine. None of the tested PAHs was found in maternal or cord blood. However, all five PAH compounds were detected in placentas; Ch was the highest (6.582 μg/kg dry wt.), and BaA was the lowest (0.236 μg/kg dry wt.). The mean concentration of urinary 1-HP found in this study was 0.216 ± 0.856 μg/g Cr. After adjusting for gestational age and other confounding variables, regression models revealed an inverse relationship between placental weight, cord length and placental BaP. A similar trend was observed between cord length and ∑4-PAHs in placental tissues. Urinary 1-HP, though, cannot be used as an unequivocal biomarker of PAH exposure, but it can be an appropriate indicator of exposure to environmental tobacco smoke (ETS). The data demonstrate that ETS exposure (as measured by urinary COT) may adversely affect birth outcome as shown by reduced head circumference, birth weight, and birth length, as well as increased cephalization index. The positive relationship between 8-OHdG levels and 1-HP in urine provides evidence of an oxidative stress mechanism. Although this study provides no direct evidence of an association between PAH exposure and DNA damage, increased oxidative stress in the form of lipid peroxidation significantly affected various birth measures. Therefore, there is a need for studies regarding PAH exposure and its associated biological effects to determine the extent of potential fetal damage as well as possible long-term effects, such as cancer.

We examined the effect of mercury (Hg) associated with dental amalgam fillings on biomarkers of renal and oxidative stress in children between the ages of 5-15.5 years. Urine samples were analyzed for N-acetyl-β-D-glucosaminidase (NAG), α(1)-microglobulin (α(1)-MG), β(2)-microglobulin (β(2)-MG), retinol binding protein (RBP), albumin (ALB), 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The level of urinary Hg (UHg-C) was calculated as μg/g creatinine. Multiple regression analyses revealed that the excretion of urinary NAG was significantly associated with the presence of dental amalgam fillings (β=0.149, P=0.03) and the levels of UHg-C (β=0.531, P=0), with an interaction between the two (P=0). The increase in urinary NAG in relation to UHg-C levels had a dose-effect pattern. The lowest observed effect was seen at UHg-C levels above 1.452 μg/g creatinine, which is lower than previously reported. In contrast, α(1)-MG was negatively associated with the presence of dental amalgam fillings (β=-0.270, P=0), but positively with UHg-C levels (β=0.393, P=0). There were 7 children without, and one child with, dental amalgam fillings with urinary α(1)-MG levels above the reference limit of >7 mg/g creatinine. Even though α(1)-MG seems to be a reliable biomarker for early changes in renal functions, it might exert its effect only at a higher level of exposure. An inverse relationship was also observed between urinary 8-OHdG levels and the presence of dental amalgam fillings. This might suggest that the dental amalgam does not increase DNA damage but reduces the capacity to repair DNA, leading to lower urinary excretion of 8-OHdG. On the other hand, we found that Hg affected the excretion of urinary 8-OHdG in a dose-related pattern that was mostly associated with long-term exposure to low Hg levels. Urinary NAG levels were positively associated with urinary MDA levels (β=0.516, P=0) but not with 8-OHdG (β=0.134, P=0.078) after adjustment for potential confounders. Both UHg-C and the presence of dental amalgam fillings remained predictors of the NAG model. Our data provide evidence that low exposure to Hg from dental amalgam fillings exerts an effect on kidney tubular functions in children. Oxidative stress may have played a role in this mechanism. The results of this study would also suggest that urinary NAG is the most sensitive of all the investigated renal biomarkers. These results should be confirmed with further investigation.

Previous studies of in utero exposure to dichlorodiphenyltrichloroethane (DDT) have shown mixed results for the harmful effects on fetal growth and development. This cross-sectional study was designed to: (1) examine the extent of DDT exposure in 1578 women, aged 28.5 ± 6.0 who delivered between June 2005 and 2006 in the area of Al-Kharj, Saudi Arabia; and (2) assess its influence on neonatal anthropometric measurement of newly born babies. DDT and its metabolites, namely 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p′-DDE), 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane (p,p′-DDD) and 1,1,1-trichloro-2,2′ bis (p-chlorophenyl) ethane (p,p′-DDT) were measured in cord and maternal serum as well as placenta by Gas Chromatography coupled with an Electron Capture Detector (GC/ECD). p,p′-DDE was detected in 28.3% of cord and 54.4% of maternal serum, reflecting past exposure, whereas the p,p′-DDT was only found in 0.46% cord and 1.2% maternal samples. As expected the p,p′-DDE cord levels (0.197 ± 0.961 μg/L) were 2.8 times lower than the maternal levels (0.551 ± 1.778 μg/L), and both were significantly correlated (r = 0.517) suggesting its transplacental transfer. The picture was different in placental tissues. p,p′-DDE and p,p′-DDT were detected in 84% and 99% of placental tissues, with the highest p,p′-DDT in placental tissues (29.62 ± 158.282 µg/kg dry wt.) compare to p,p′-DDE (10.167 ± 18.851 μg/kg dry wt.). In general, the presence of DDT metabolites in our participants indicates that these chemicals are still relevant despite the fact that they have been banned or restricted in the study area for many years. Our results support the view for an association between low in utero exposure to DDT and the anthropometric development of the fetus leading to a reduction in its head circumference, crown–heel length, birth weight and birth height. Since the reduction in these measures was independent of gestational age and/or preterm births, our findings suggest a detrimental effect of the DDT exposure on fetal growth. Neonatal anthropometric measures are considered as an important tool to detect newborns at higher risk of morbidity and impairment of growth. Efforts should be made to decrease exposure of women of reproductive age and to examine maternal DDT exposure in relation to long-term impact on health.

Skin-lightening creams are extensively promoted online and in the media. They may contain a wide variety of active ingredients such as mercury, hydroquinone, and steroids that are highly toxic, especially after prolonged application. For more than a decade, we found high mercury content in many products sold on Saudi markets. Some of these products were later banned by the government. However, the presence of other ingredients has not been documented. We undertake this study on some of the most popular skin-lightening creams on the market to test for toxic ingredients such as mercury, titanium dioxide, hydroquinone, and corticosteroids. A total of 33 different brands were selected for the analysis of titanium (50 samples), hydroquinone (55 samples), and corticosteroids (56 samples) with the exception of mercury in which only 23 brands (34 samples) were tested. This study showed that 2 of 34 skin-lightening creams had mercury above the US FDA limit of 1 µg g−1. All products had titanium dioxide at less tha...

Cosmetics still retain their glittering appeal, but public concern about their toxicity has become a hot issue. Trace amounts of toxic metals can be either intentionally added to cosmetics or present as impurities in the raw materials. We therefore assessed the levels of lead, cadmium, nickel, chromium, mercury, antimony, and arsenic in 14 brands of lipstick (28 samples) that are widely available in local Saudi markets. This study found that the levels of all metals were generally lower than the specifications of the US Food and Drug Administration for metallic impurities in color additives used in cosmetics. Only one brand of lipstick exceeded the specifications, containing levels of arsenic higher than 3 ppm. Also, the levels of nickel and chromium contents in 10 and 4 of the 28 lipsticks, respectively, were above 1 ppm, the trigger limit of allergic contact dermatitis (ACD). Despite the metallic contents in lipsticks being below the acceptable limits for impurities in color additives used in the cosmet...

This study was designed to determine the status of selenium, dl-alpha-tocopherol, and all-trans-retinol in adults living in Al-Kharj district using serum and toenail samples, and to look for possible association between these parameters and the etiology of endemic diseases in the same area. For this purpose, we examined a cross section of samples of 743 healthy Saudi adults on routine visits to the Primary Health Care Unites (PHCUs) for different common health problems. The arithmetic mean for selenium, dl-alpha-tocopherol, and all-trans-retinol in serum and toenail selenium levels were 107.045 +/- 23.045 microg/l (n = 743, range 52.600-210.120 microg/l), 1.053 +/- 0.324 mg/dl (n = 737, range 0.29-3.42 mg/dl), 52.561 +/- 25.671 microg/dl (n = 743, range 11.20-400.85 microg/dl), and 0.634 +/- 0.221 microg/g (n = 691, rangeDL - 1.797 microg/g), respectively. The average serum selenium concentration seems to be satisfactory and compares favourably with high selenium intake countries. Although none of our participants exhibited serum selenium deficiency (45 microg/l), 41% of our participants had toenail selenium0.56 microg/g reported low levels in the previous study. The mean serum dl-alpha-tocopherol concentrations fall within the upper limit of the normal range of0.698-1.981 mg/dl for alpha-tocopherol as found in previous studies. On the other hand, the mean serum all-trans-retinol is higher than the normal range (20-30 microg/dl). None had exhausted retinol stores trans-retinol and MDA levels in the serum was found as a sign of peroxidative lipid damage, confirming the role of vitamin A in reducing oxidative stress. Our data also revealed a link between the status of selenium, dl-alpha-tocopherol and all-trans-retinol and a number of health problems. However, these observations need larger epidemiological studies for further confirmation.

A total of 1016 healthy Saudi mothers and their respective infants (aged 3-12 months) were recruited from 57 Primary Health Care Centers (PHCCs) in Riyadh, Saudi Arabia, to evaluate the extent of mercury (Hg) exposure and predict its sources in the healthy Saudi population. Total Hg levels were measured in maternal urine, breast milk, blood, and hair and in the infants' urine and hair. Only 1.9% of the mothers had urinary Hg (UHg)>10 μg/l, the limit for asymptomatic adults recommended by the World Health Organization, but the median (0.99 μg/l) was higher than in other countries. Also, 49.3% of the mothers had UHg>1 μg/l, the German reference value for adults. Median infant UHg was 0.729 μg/l, and 77 and 93 % of the infants had levels higher than 0.4 and 0.1 μg/l, the reference values of the Centers for Disease Control and Prevention and for Germany, respectively. The median Hg level in breast milk was 0.884 μg/l. Even though 43.2% of the milk samples were above the background level for Hg in human milk (1 μg/l), our results were lower than those reported from other countries. Median maternal total Hg in blood was 0.637 μg/l, and only 0.4 and 6.9% of samples were higher than the Hg reference levels of 5.8 μg/l of the Environmental Protection Agency (EPA) and of 2 μg/l for Germany, respectively. Total Hg levels in hair (HHg) varied widely among mothers and infants, but only 3.9% of the mothers and 2.8% of the infants had HHg>1 μg/g (the EPA reference level). Median HHg values were 0.117 μg/g dry weight in mothers and 0.1 μg/g dry weight in infants; both were lower than in other countries. The Hg levels in mothers and their respective infants were relatively low, but our results were consistent with other studies indicating that dental amalgam fillings and fish consumption were the main predictors of maternal Hg exposure. Among the several biomarkers of Hg exposure, Hg levels in maternal hair and urine were the strongest predictors of infant exposure. The lack of an association between Hg in breast milk and Hg in infant urine and hair suggested that the infants were exposed to Hg predominately during pregnancy rather than during breastfeeding. We expect that our data can serve as a baseline for further biomonitoring and follow-up studies, particularly of the long-term impact of Hg on childhood neurodevelopment.

The seeds of Nigella sativa are used commonly in the Middle East as a traditional medicine to treat a variety of health conditions. This paper examines the levels of selenium, dl- α -tocopherol, dl - γ -tocopherol, all- trans -retinol, thymoquinone and thymol in different brands of N. sativa seeds purchased from local markets in Riyadh, Saudi Arabia. Selenium was determined by the inductively coupled plasma spectrometry coupled with the hydride system. dl - α -tocopherol, dl - γ -tocopherol, all- trans -retinol, thymoquinone and thymol were measured by high-performance liquid chromatography. The average mean concentrations (mg/kg fresh weight) of selenium, dl - α -tocopherol, dl - γ -tocopherol, all- trans -retinol, thymoquinone and thymol in all tested seeds were 0.17±0.10, 9.02±4.84, 5.42±3.96, 0.27±0.27, 2224.49±1629.50 and 169.35±100.12, respectively. The concentrations of these analytes were significantly affected by the country of origin of the N. sativa . It is concluded that N. sativa provides an important source of antioxidants.

Purpose. To determine the status of selenium, dl‐α‐tocopherol and all‐trans‐retinol in children and adults living in the Al‐Kharj district, using serum and toenail samples. Design. A cross‐sectional study. The samples were collected randomly from 1255 healthy Saudi subjects attending the Primary Health Care Units (PHCUs), Al‐Kharj for different common health problems.Materials and methods. Serum and toenail selenium concentrations were measured using an atomic absorption spectrophotometer coupled with an electrothermal temperature controller, whereas the levels of dl‐α‐tocopherol, all‐trans‐retinol and malondialdehyde in serum were determined using high‐performance liquid chromatography.Results. The arithmetic means of selenium, dl‐α‐tocopherol and all‐trans‐retinol in serum for the tested population were 102.165±22.936 µg l−1 (n = 1255, range 18.25–210.12 µg l−1), 22.715±6.908 µmol l−1 (n = 1250, range 2.53–79.44 µmol l−1) and 1.601±0.802 µmol l−1 (n = 1256, range 0.39–13.99 µmol l−1), respectively. Toen...

Lead, cadmium, and mercury concentrations were determined in breast milk of Saudi lactating mothers from Riyadh and Al-Ehssa regions in Saudi Arabia who were not occupationally exposed. The mean levels for cadmium, lead, and mercury were 1.732 microg/L, 31.671 microg/L, and 3.100 microg/L, respectively. In contrast to mercury, mothers living in the Al-Ehssa region had significantly higher cadmium and lead concentrations in their breast milk than those in the Riyadh region. The estimated weekly intakes of cadmium, lead, and mercury of breast-fed infants in this study were in some cases higher than the Provisional Tolerance Weekly Intake (PTWI) recommended by FAO/WHO, which pose a threat to their health. This necessitates the urgent need to undertake a comprehensive study to determine the sources of exposure to these heavy metals. Breast-feeding is of great beneficial value for the infant's development; therefore, efforts should be made to prevent its contamination with environmental pollutants.

A gas chromatography-mass spectrmetroic (GC-MS) method was developed to measure six polycyclic aromatic hydrocarbons (PAHs) in 54 fish samples. Five fish species highly consumed by the local population (shrimps, Emperors, Rabbitfish, Doublebar Bream and Greasy Grouper) were selected from three different sites on the Gulf coast of Saudi Arabia where agricultural, municipal and petroleum industry activities take place. Variations in PAH levels among the three sites were not significant. Total concentrations of PAHs benzo(a)anthracene, chrysene, and benzo(b)fluoranthene ranged from non-detectable to 44.9 microg kg(-1). In this study, concentrations of benzo(a)anthracene, chrysene, benzo(b)fluoranthene and total PAHs greater than the acceptable tolerance limit (1 microg kg(-1)) were found in 68.5, 40.7, 51.9 and 83.3% of the fish samples, respectively. PAH contents in fish vary considerably with species; Doublebar bream contain the highest while shrimps contain the lowest. This pilot study clearly shows that the consumption of fish could be a source of exposure of the local population to PAHs. Since there is a consensus on the substantial contribution of PAHs to cancer in humans, it would be interesting to conduct further research in order to determine the magnitude of the problem along other coastal regions of Saudi Arabia.

Comparative analytical quantitation of DDE, DDD, and DDT in human milk, by gas chromatography with mass spectrometric and electron capture detection (GC-MS and GC-ECD) has been studied by use of 513 samples of milk from lactating mothers participating in a World Health Organization special study. Although Correlation between thep,p-DDE concentrations measured by GC-ECD and GC-MSD was excellent (r=0.950,P

To our knowledge, this study may be the first to examine the antagonistic role of selenium (Se) on oxidative stress induced by cadmium (Cd) and its impact on birth measures. Cd and Se levels were measured in umbilical-cord blood and the placentas of a subsample of 250 healthy mothers who participated between 2005 and 2006 in the project "Prenatal Exposure to Pollutants". The median Cd levels in cord and maternal blood and placental tissue were 0.78μg/l, 0.976μg/l and 0.037μg/g dry wt., respectively. The median levels of Se in cord serum and placental tissue were 65.68μg/l and 1.052μg/g dry wt., respectively. Se was more than 100-fold in molar excess over Cd in both cord serum and placental tissue. The median molar Cd/Se ratios in cord serum and placental tissue were 0.008 and 0.024, respectively, which were much lower than unity. This study suggests that both Cd and Se play a role in the mechanism of oxidative stress, but, the process underlying this mechanism remains unclear. Nevertheless, three biomarkers of oxidative stress had inconsistent relationships with Cd and/or Se in various matrices, perhaps due to potential untested confounders. Our results generally support an association between low in utero exposure to Cd and the anthropometric development of the fetus. Adjusted regression models indicated a negative association of cord blood Cd levels ≥0.78μg/l with Apgar 5-min scores and birth height. Maternal Cd levels ≥0.976μg/l were associated with a 5.94-fold increased risk of small-for-gestational-age births, which increased to 7.48-fold after excluding preterm births. Placenta weight decreased with increasing placental Cd levels ≥0.037μg/g dry wt. (p=0.045), an association that became stronger after excluding preterm births or adjusting for birth weight. Cord Se levels ≥65.68μg/l were positively associated with placenta weight (p=0.041) and thickness (p=0.031), an association that remained unchanged after excluding preterm births. Cord Se levels, however, were negatively associated with cephalization index, but only after excluding preterm births (p=0.017). Each birth measure was again modeled as a function of the Cd/Se ratios in cord blood and placenta tissue. Interestingly cord ratios ≥0.008 were negatively associated with Apgar-5min score (p=0.047), birth weight (p=0.034) and placenta thickness (p=0.022). After excluding preterm births, only the association with placenta thickness remained significant (p=0.021), while birth weight (p=0.053) was marginally significant. In contrast, cephalization index increased with Cd/Se ratios ≥0.008 (p=0.033), an association that became marginally significant after excluding preterm births (p=0.058). For placental Cd/Se ratios ≥0.024, only placenta weight was reduced with (p=0.037) and without (p=0.009) the inclusion of preterm births. These findings do not support an antagonistic mechanism between Cd and Se. The role of oxidative mechanisms either induced by Cd exposure or alleviated by Se on these birth anthropometric measures was examined by principal component analysis. Se did not have a clear protective role against Cd-induced adverse effects despite its substantial excess over Cd, and its role in alleviating oxidative stress by reducing malondialdehyde levels. The results may suggest that the extent of the Se beneficial effects is not governed only by its concentration but also by the chemical forms of Se that interact with various proteins. Consequently, the speciation of Se in such studies is essential for understanding and predicting Se availability for absorption.

In an attempt to know whether highly consumed food might contribute to metal exposure, we analyzed cadmium, lead, and mercury in 27 rice grain samples commonly consumed in Saudi Arabia by atomic absorption spectrometry after acid digestion. The mean concentrations and ranges of cadmium, lead, and mercury in tested rice samples were 20.261 (rangeDL-178.026 microg/kg), 134.819 (range 23.1-1529.0 microg/kg), and 3.186 (rangeDL-43.573 microg/kg), respectively. The results showed high concentrations of metals and in some cases exceeded the Provisional Tolerance Weekly Intake (PTWI) recommended by FAO/WHO. It was also noted that different rice grain samples had varying concentrations of these metals. Because the bulk of literature warns against the cumulative effects of prolonged heavy metal exposure, regular consumption of rice by local populations might pose potential health problems.

This cross-sectional study examined the association between blood lead levels and neuropsychological and behavioural problems of 533 schoolgirls (6-12 years of age) who attended public schools in Riyadh, Capital of Saudi Arabia. Regression models were used to determine the best predictors of Beery VMI Saudi-based standard scores, TONI Saudi-based scores and rank percentile. The mean blood lead level was 8.11 +/- 3.50 micrograms/dl in the range of 2.3 to 27.36 micrograms/dl. Significant negative associations were noted between blood lead levels and Beery VMI Saudi-based standard scores as well as rank percentile. Lead had no effect on TONI Saudi-based standard scores. Beery VMI Saudi-based standard scores, TONI Saudi-based standard scores and rank percentiles were inversely related to pupils with blood lead levels9 micrograms/dl. These findings attest an association between neuropsychological and behavioural impairment and lead exposure at blood lead levels in the range of 9.02 to 27.36 micrograms/dl. The results of this study should be seriously considered by public health authorities to give more attention to this pediatric health problem.

The fluoride concentration in the urine samples of 130 Saudi individuals aged 16-70 years old living in Riyadh was determined using a fluoride-specific electrode (0.9262 ± 0.703 μ g ml−1, 0.16-4.68 μ g ml−1). There were differences in the urinary fluoride levels of the subjects. About 45.5% of the subjects had urinary fluoride less than 0.7 μ g ml−1. Conversely, 22.3% of the screened subjects had urinary fluoride levels higher than 1.2 μ g ml−1; this could increase the risk of dental and skeletal fluorosis. Since drinking water is considered to be the major source of fluoride, it was measured in 88 drinking water samples. Significant correlation between fluoride in urine and drinking water was found (r = 0.4341, p = 0.0237). Bottled water had significantly higher fluoride content (0.5205 ± 0.322 μ g ml−1) than tap drinking water (0.1046 ± 0.0447 μ g ml−1). About 67% of the screened water samples had low fluoride concentrations (< 0.3 μ g ml−1) which is far below the recommended level for caries control.

Selenium (Se) was measured in 300 umbilical cord blood samples collected from healthy pregnant women who live in Al-Kharj area in Saudi Arabia by means of Inductively Coupled Plasma Spectrometry with the hydride t-system. The selenium concentration found in the serum of 300 newborns was 40.847 ± 8.969 μpg/L. Preterm infants had significantly lower serum selenium concentrations than full-term infants (32 ± 8.029 μg/L versus 41.323 ± 8.784 μg/L). Significant positive correlations were found between selenium levels and birth weight. Results of this study suggest that low selenium levels of new-borns in Al-Kharj may reflect an inadequate maternal dietary intake.

Blood samples from 240 Saudi children aged 1 day-72 months old were analysed for zinc protoporphyrin (ZPP), lead (Pb) and hematological parameters. Elevated blood zinc protoporphyrin concentrations ( >3.3 mug/g Hb) were found in 50.8%. These children had a mean blood ZPP concentration of 6.857 4.925 mug/g (3.35-43.7 mug/g). Blood lead levels >10 mug/dl were found in 8 children in the range of 10.45-61.08 mug/dl. On the other hand, Hb less than 11 g/dl were found in 51.6%. The correlation coefficient between the concentration of ZPP and the hematological parameters and age were tested. Significant negative correlation were found between ZPP concentrations and Hb, HCT, RBC and age. We conclude that the use of hematofluorometer to measure ZPP proved to be an effective and inexpensive screening tool for iron deficiency in children especially in communities where the prevalence of iron deficiency is high.

The influence of application of skin-lightening creams and dental amalgam fillings on the urinary mercury (Hg) level was evaluated in 225 females (ages 17 to 58 years) living in Riyadh, capital of Saudi Arabia. The arithmetic mean of the urinary Hg level was 6.96 ± 20.43 μg l, in the range 0 to 204.8 μg l. The mean urinary Hg level adjusted by creatinine (Cr) was 11.22 ± 37.23 μg g Cr, in the range 0 to 459.37 μg g. No significant difference in urinary Hg was noted between the females regarding the use of skin-lightening creams. On the other hand, results showed that urinary Hg concentration was influenced by the use and number of dental amalgam fillings. No women were identified with symptoms or signs that could be attributed to Hg intoxication. Urine analyses for creatinine, urea, uric acid, phosphorus, magnesium, glucose and calcium showed significant correlation with urinary Hg. This suggests that chronic exposure to Hg may be associated with a deterioration of renal function.

Twenty-four brands of commercial infant milk formula were collected and analysed for selenium by inductively coupled plasma spectrometry with the hydride t-system after an acid digestion procedure. The mean selenium concentration was 49.0 ± 11.55 μg l, with a range from 26-68 μg l, resulting in an adequate daily selenium intake for infants aged from zero to six months consuming 0.75 l milk daily as set by the US National Research Council in 1989.