Interaction between cadmium (Cd), selenium (Se) and oxidative stress biomarkers in healthy mothers and its impact on birth anthropometric measures.

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.

Mercury (Hg) and oxidative stress status in healthy mothers and its effect on birth anthropometric measures.

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 <20µg/l (the threshold limit of Keshan disease). More than 80% of the newborns, though, had Se levels below the 80µg/l needed for maximum glutathione peroxidase activity. Even though 18.6% of the newborns had levels of Hg ≥5.8µg/l (the reference dose of the Environmental Protection Agency), no relationship was observed with the biomarkers of oxidative stress. The mean placental Hg levels (0.056±0.075µg/g dry wt.) were higher than those reported for newborns with abnormal fetal development. Our study also documented significant placental transfer of Hg and Se to the fetus. The Hg/Se molar ratio in both cord blood and placental tissue was well below 1. The average amount of Se in both matrices was approximately 50-fold in molar excess over Hg. The molar excess of Se in the umbilical cord (0.843µmol/l), however, was lower than in placental tissues (13.098µmol/kg dry wt.). In further support of the relationships of Hg and Se on oxidative stress, we observed significantly lower levels of maternal MDA associated with Se levels in both cord blood and placental tissues and significantly higher TM levels associated with placental Hg in both newborns and their mothers. In contrast, Se/Hg molar ratios in placental tissues were positively associated with MDA and negatively with TM. The disproportion between Hg and Se might be influenced by the length of Hg exposure that in turn might affect Se bioavailability. Each birth anthropometric outcome was modeled as a function of Hg, Se and their interactions. After an adjustment for confounding variables, Hg in cord blood had a significantly positive rather than the expected negative association with crown-heel length. Placental Hg was associated with reduced birth height. Both associations were independent of prematurity. The status of Se in newborns was positively associated with crown-heel length and placental weight, with and without preterm births, and with birth weight, but only without preterm births. In contrast, a lower cephalization index was correlated with Se levels in cord blood, which may be an indicator of a detrimental effect on health. Our study, however, revealed associations between significantly lower levels of placental Se and several birth anthropometric measures (head circumference, birth weight and birth height) but the significance disappeared after excluding preterm births. Regression analyses generally indicated either significant or marginally significant Hg-Se antagonistic interactions that may have moderated the toxic effect of Hg on head circumference and birth weight. This finding may be due to chance or residual confounding and so may not be clinically relevant, but it may also suggest that Hg, Se and Hg-Se interactions are important factors for understanding Hg-induced adverse birth outcomes. Additional research will be necessary to evaluate the biological impact of combined metals in the assessment of fetal growth and development.

Birth outcome measures and maternal exposure to heavy metals (lead, cadmium and mercury) in Saudi Arabian population.

This cross-sectional study was conducted to assess the association between exposure to heavy metals (lead, cadmium and mercury) during pregnancy and birth outcomes in 1578 women aged 16-50 years who delivered in Al-Kharj hospital, Saudi Arabia, in 2005 and 2006. The levels of lead, cadmium and mercury were measured in umbilical cord blood, maternal blood and the placenta. Outcome variables were anthropometric measures taken at birth, along with the risk of being small-for-gestational age (SGA). We selected the 10th percentile as the cutoff for dichotomizing measures of birth outcome. Cadmium, despite its partial passage through the placenta had the most prominent effect on several measures of birth outcome. After adjustment for potential confounders, logistic regression models revealed that crown-heel length (p=0.034), the Apgar 5-minute score (p=0.004), birth weight (p=0.015) and SGA (p=0.049) were influenced by cadmium in the umbilical cord blood. Significant decreases in crown-heel length (p=0.007) and placental thickness (p=0.022) were seen with higher levels of cadmium in maternal blood. As placental cadmium increased, cord length increased (p=0.012) and placental thickness decreased (p=0.032). Only lead levels in maternal blood influenced placental thickness (p=0.011). Mercury in both umbilical cord and maternal blood was marginally associated with placental thickness and placental weight, respectively. Conversely, placental mercury levels significantly influenced head circumference (p=0.017), the Apgar 5-minute score (p=0.01) and cord length (p=0.026). The predictions of these models were further assessed with the area under the curve (AUC) of the receiver operating curves (ROCs), which were modest (larger than 0.5 and smaller than 0.7). The independence of gestational age or preterm births on the observed effect of metals on some measures of birth outcome, suggested detrimental effects of exposure on fetal development. The magnitude of the estimated effects might not necessarily be of clinical significance for infants but may have a considerable public-health relevance given the high prevalence of exposure to heavy metals. Further research should be conducted to confirm these findings and to evaluate their long-term risks, if any.

Mercury (Hg) exposure in breast-fed infants and their mothers and the evidence of oxidative stress.

The objective of this work was to assess exposure to mercury (Hg) and its induction of oxidative stress in 155 healthy lactating Saudi mothers and their infants. Samples of breast milk and blood were collected from the mothers, while urine was taken from both infants and mothers. Both urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured in mothers and infants as biomarkers of oxidative stress. The mean concentration of Hg in breast milk was 1.19 µg/L (range 0.012-6.44 µg/L) with only one mother having Hg >4 µg/L, the upper limit established by the US Agency for Toxic Substance and Disease Registry. However, 57.4 % had Hg ≥1 µg/L, the background level for Hg in human milk. The mean urinary Hg corrected for creatinine (Hg-C) in mothers and infants was 1.47 and 7.90 µg/g creatinine, respectively, with a significant correlation between the two (p < 0.001). Urinary Hg levels over 5 µg/g creatinine (the background level in an unexposed population) were found in 3.3 % of mothers and 50.1 % of infants. None of the mothers had total blood Hg above the US Environmental Protection Agency's maximum reference dose of 5.8 µg/L. No correlation was noted between urinary Hg in infants and Hg in breast milk (p > 0.05). Hg in breast milk, though, was associated with Hg in blood (p < 0.001), suggesting the efficient transfer of Hg from blood to milk. Hg in the breast milk of mothers and in the urine of infants affected the excretion of urinary MDA and 8-OHdG, respectively, in a dose-related manner. These findings reveal for the first time lactational exposure to Hg-induced oxidative stress in breast-fed infants, which may play a role in pathogenesis, particularly during neurodevelopment. This will also contribute to the debate over the benefits of breast milk versus the adverse effects of exposure to pollutants. Nevertheless, breastfeeding should not be discouraged, but efforts should be made to identify and eliminate the source of Hg exposure in the population.

Polycyclic aromatic hydrocarbons (PAHs) as determinants of various anthropometric measures of birth outcome.

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.

Phthalates residues in plastic bottled waters.

This study was conducted to determine the presence of phthalates in 10 different brands of bottled water available in Saudi markets and stored under different conditions. Dimethyl phthalate (DMP), diethylphthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP) and diethyl hexyl phthalate (DEHP) were measured by headspace solid-phase microextraction followed by gas chromatography- mass spectrometer detector. Most of these phthalates were detected in the selected bottled water sample that might be either leached from the plastic packaging materials or contamination during bottling processes. Bottled waters stored at 4°C contained higher levels of DMP, DEP, BBP and DEHP than those stored at room temperature and outdoors. On the other hand, the levels of DMP, DEP and BBP were significantly lower in bottled waters stored at room temperature than those outdoor. It seems that temperature and sunlight play a role in the degradation of phthalates within time. The levels of BBP were the highest at 4°C storage (4.592 ± 3.081 µg/l; range: 1.194-21.128 µg/l) and approximately 76% of the bottled waters had BBP above the limit of quantification (LOQ) of 0.994 µg/l. Apart from DEHP (< 6 µg/l), there are not current legislations for other phthalates. Regardless of storage conditions, all our samples did not exceed the maximum established limit of DEHP. Although, the levels of phthalates in tested bottled waters were low, one should not dismiss that these chemicals may cause endocrine disruption through several mechanisms, especially to potentially vulnerable populations such as infants and pregnant women. Saudi Arabia ranks 12 in bottled water consumption (88 L per capita in 2004) among the 71 reported countries. With this high consumption, a quality assurance scheme for residue monitoring in water is quite important. Although, one cannot avoid phthalates contamination in bottled waters due to manufacturing process but at least special care should be taken regarding their storage conditions.

Heavy metals (lead, cadmium and mercury) in maternal, cord blood and placenta of healthy women.

Lead, cadmium and mercury were measured in placental tissue, umbilical cord and maternal blood samples of 1578 women who delivered at the Al-Kharj King Khalid Hospital between 2005 and 2006. The aim of this study was to evaluate the status of heavy metal exposure in mothers and their newborns and to identify predictors of maternal exposure. Lead was detected in all cord and maternal blood and in 96% of placental tissues. Only in 0.89% and 0.83% of cord and maternal blood samples were the levels of lead above the CDC threshold limit of 10 µg/dl. Maternal blood lead was also higher (2.3%) than the German Reference value in women of 7 µg/dl. Approximately 9.3% of women had a placental lead above the 95th percentile in the range of 0.83-78 µg/g dry wt., a level of possible developmental toxicity. Cadmium was detected in 94.8% and 97.9% of cord and maternal blood samples respectively, though only five newborns had a cadmium level above the OSHA threshold limit of 5 µg/l. Comparing our results to the newly revised German Reference value for nonsmokers, 48.6% of mothers had blood cadmium levels >1.0 µg/l. We found as well that 25% of women had placental cadmium in the >75th percentile, in the range of 0.048-4.36 µg/g dry wt., which is likely to affect fetal growth and development. Of the maternal and cord blood samples, 11.2% and 13%, respectively, had mercury levels >5.8 µg/l, which is the EPA reference dose. Nearly 49% of women had mercury levels >2.0 µg/l, the German Reference value for those who consume fish ≤3 times a month. Around 50% of the mothers had placental mercury in the range of 0.031-13.0 µg/g dry wt. Regression analyses indicated that the levels of metals in the blood and placenta were influenced by several factors. This study provides informative baseline biomonitoring data and reveals a substantial exposure to heavy metals in non-occupationally exposed Saudi mothers and their newborns that might jeopardize the health of both. Additional research is also urgently needed to explore factors such as environment, diet, lifestyle and/or cultural habits contributing to maternal and fetal exposures. Preventive measures to eliminate or minimize the unnecessary risk of fetus exposure to heavy metals or other pollutants during pregnancy should be initiated once these factors are identified.

Assessment of lead in cosmetic products.

There have been a number of recent reports in the media and on the internet about the presence of lead in brand-names lipsticks. This has drawn our attention to assess the safety of various cheap brands of cosmetics sold at 2-riyals stores in Saudi market that are imported from countries where safety regulations are poorly enforced as well as they lack perfect conditions for manufacturing. Lead contents were determined in 26 and eight different brands of lipsticks and eye shadows using the Zeeman atomic absorption spectrophotometer coupled to graphite tube atomizer after an acid digestion procedure. Lead was detected in all the studied samples. The median (25th-75th percentile) lead content in 72 lipsticks samples was 0.73 (0.49-1.793) PPM wet wt. in the range of 0.27-3760 PPM wet wt. There were four brands of lipsticks with lead content above the FDA lead limit as impurities in color additives (20 PPM). The FDA does not set a limit for lead in lipstick. Three of them were extremely high points and considered outliers. The median (25th-75th percentile) lead contents in pressed powder eye shadow was 1.38 (0.944-1.854) PPM wet wt. (n=22) in the range of 0.42-58.7 PPM wet wt. One brand was above 20 PPM the US FDA's lead limit as impurities. The overall results indicate that lead in lipsticks and eye shadows are below the FDA lead limit as impurities and, thus, probably have no significant toxicological effects. Nevertheless, few brands had lead content above 20 PPM that might put consumers at the risk of lead poisoning. Lead is a cumulative, and applying lead-containing cosmetics several times a day or every day, can potentially add up to significant exposure levels. Pregnant and nursing mothers are vulnerable population because lead passes through placenta and human milk and affect fetus or infant's developments. Our findings call for an immediate mandatory regular testing program to check lead and other toxic metals in lipsticks and other cosmetic products imported to Saudi Arabia in order to curtail their excess and safeguard consumer health.

Accumulation of mercury in ovaries of mice after the application of skin-lightening creams.

Skin-lightening creams are being increasingly used by women in particular, worldwide in an attempt to whiten their skin. Men and older people use these creams to remove age spots or other pigmentation disorders. Several studies have reported the presence of high mercury levels in skin-lightening cream. Women, especially pregnant and nursing mothers, who use these creams are at risk of mercury toxicity because long-term exposure can cause permanent neurological damage, nephrological disorders, fertility problems, and birth defects. Early exposure usually has no clinical symptoms. Mercury levels were measured in a total of 49 ovary tissue samples. The mean mercury contents in the ovaries of non-treated mice (11.70 +/- 13.38 ng/g) were compared to mice treated with Rose skin-lightening cream samples (2,471.92 +/- 1,336.31 ng/g) and those treated with Fair & Lovely skin-lightening creams (58.47 +/- 39.51 ng/g). The mercury content in the ovary tissues increased with number of cream applications and were highest in the ovaries of mice treated twice a day with Fair & Lovely (87.79 +/- 26.20 ng/g) and once a day with Rose (3,515.61 +/- 1,099.78 ng/g). Our data indicate that dermal exposure to mercury can result in a significant accumulation in the ovaries of mice following the application of skin-lightening cream. This may cause alterations in reproductive behavior and contribute to infertility or ovarian failure. Of course, these results need to be confirmed by further research. Imported or locally made skin-lightening creams are widely available in Saudi market. It would be ideal to ban the sale of these creams but unfortunately, advertisements in the mass media presenting celebrities and beauty specialists make these products more popular. Alternatively, public health authorities should encourage more reliance on prescribed creams for the treatment of skin pigmentation problems.

Prenatal and postnatal lead exposure and early cognitive development: longitudinal study in Saudi Arabia.

The goal of this study was to assess the effect of prenatal and postnatal lead exposure on early cognitive development of infants using the Bayley Scale of Infant Development (BSID-I) at the age of 6, 12, 18, and 24 months in a longitudinal study. Based on the results of 653 cord blood lead levels, infants were classified into three groups for neuropsychological assessments: low lead risk (<10th percentile) and high lead risk (>10th percentile) of the distribution of cord blood lead level were designated as low (< or = 1.045 microg/dL) and high (> or = 3.466 microg/dL) lead risk groups. Blood lead levels in between the <10th and >90th percentile were designated as mid lead risk group. A total of 66 infants were supposed to be selected from each group for a follow-up study. Of these, only 106 participated 6 months after the study. During the follow-up study, the dropout was very high with attrition rates of 74.5%, 52.8%, and 39.6% during the 12, 18, and 24 months. Mean blood lead levels increased from 3.36 to 4.45 microg/dL between the ages of 6 and 24 months, but the standardized Mental Development Index (MDI) and Psychomotor Development Index (PDI) decreased from 99.26 and 98.13 (6 months old) to 93.29 and 82.52, respectively (24 months old). Due to the high rate of attrition, most of the infants in the low group were lost. Therefore, we used the 75th percentile of blood lead levels as a cutoff in the statistical analyses. After adjustment for a large number of confounding variables, prenatal lead exposure was found to be significantly associated with the standardized MDI and PDI scores at the age of 6 months old with a P value of 0.02 for both. A borderline significant effect of prenatal lead exposure was also seen on standardized PDI scores at the age of 24 months (P = 0.09). On the other hand, no relationship was seen between postnatal blood lead levels and concurrent cognitive development scores. Such an observation is not conclusive because of low statistical power due to small sample size. Our results provide additional evidence for low prenatal lead exposure effects on cognitive development in Saudi infants living in a rural area.

Role of Nigella sativa and a number of its antioxidant constituents towards azoxymethane-induced genotoxic effects and colon cancer in rats.

This study examined the chemopreventive effect of Nigella sativa and some of its antioxidant constituents on a number of colon cancer biomarkers in rats induced with azoxymethane (AOM). Sixty male Sprague-Dawley rats were randomly assigned into ten subgroups: vehicle (1-5) and experimental (6-10). The rats in each group were fed one of the following diets: basal diet, (200 mg/kg) Nigella sativa, (0.2 mg/kg) selenium, (1.2 mg/kg) all-trans-retinol plus (100 mg/kg) DL-alpha-tocopherol and (10 mg/kg) thymoquinone, respectively. Only rats in subgroups 6-10 were injected with AOM (15 mg/kg) once per week for 2 weeks. Both groups were fed their respective diets for 5 weeks. Then they were killed and examined for colonic aberrant crypt foci (ACF). Our result showed that only vitamin supplementation was effective on ACF. Nigella sativa revealed inhibitory effects only on DNA damage (day 34) in the AOM-treated rat group. Alternatively, selenium, thymoquinone and vitamins inhibited the MDA content in the liver. Although the exact mechanisms involved in the protective role of Nigella sativa against the initiation of colon carcinogenesis are not clearly understood, the results suggest that its inhibitory effects might depend on the combined competitive inhibition of various antioxidant constituents of this plant.

Longitudinal study of prenatal and postnatal lead exposure and early cognitive development in Al-Kharj, Saudi Arabia: a preliminary results of cord blood lead levels.

Extensive data shows a direct link between low-level lead exposure during early development and deficits in neurobehavioral-cognitive performance evident late in childhood through adolescence. Our previous studies confirmed the transfer of lead from the mother to the fetus as well as the effect of low lead exposure on neuropsychological behavior in school children. Such results led us to design a longitudinal survey to evaluate the effect of prenatal and/or postnatal lead exposure on early cognitive development among selected group of children from birth to 2 years of age. During the first stage of this study (between March and July 2004), we measured lead levels in 653 umbilical cord blood samples taken from healthy Saudi mothers delivering at King Khalid Hospital, Al-Kharj. This gave a good opportunity to look at the prevalence of increased blood lead levels in umbilical cord blood and to identify risk factors for prenatal lead exposure. The mean cord lead levels were 2.21 +/- 1.691 microg/dl in the range of 0.284-17.276 microg/dl. Only 1.23% of the newborns had blood lead levels >10 microg/dl, the Center for Disease Control level of concern. To investigate risk factors affecting cord blood lead levels, only subjects with lead levels above the 75th percentile (2.475 microg/dl) were selected in the multiple regression models. We observed that cord blood lead levels were significantly influenced by maternal age, the location of residence and intake of prenatal supplements. Controlling for newborn's head circumferences confounders, it was found that cord blood lead levels were significantly and negatively associated with newborn's head circumference (beta = -0.158, p = 0.036). The negative association was seen between intake of prenatal supplements and cord blood lead levels emphasizing the role of prenatal supplementations during pregnancy. The significant reductions in newborns, head circumferences due to lead exposure may have serious implications for their future performance and achievement. This study reveals that even at low prenatal lead exposure, all possible measures to inspect lead sources in our environment and reduce lead exposure should be taken.

Exposure to heavy metals (lead, cadmium and mercury) and its effect on the outcome of in-vitro fertilization treatment.

We investigated the effect of lead, cadmium and mercury exposure on pregnancy and fertilization rate outcome among 619 Saudi women (age 19-50 years) who sought in-vitro fertilization (IVF) treatment between 2002 and 2003. The concentrations of lead, cadmium and mercury were measured in both blood and follicular fluids. At levels well below the current US occupational exposure limit guidelines (40microg/dL) and even less than the current Centers for Disease Control and Prevention level of concern for preventing lead poisoning in children (10microg/dL), blood lead level was negatively associated with fertilization outcome in both adjusted and unadjusted logistic regression models. We found that among various demographic, socioeconomic and environmental factors, fish consumption was positively associated with blood lead levels. These results support the hypothesis that a raised blood lead level affects infertility and intervention to reduce the lead exposure might be needed for women of reproductive age. The present results also revealed unexpected finding - the positive relationship between follicular cadmium levels and fertilization outcome, which points to the necessity for further investigation. Though adverse effect of mercury on pregnancy outcome or fertilization rate was not evident in this study, mercury5.8microg/L (EPA safety limit) was found in the blood and follicular fluid of 18.7% and 8.3% of the women, respectively. Concerns about its possible adverse effects on the physiology of reproduction or fetal development cannot be ruled out. It should be noted that skin-lightening creams and dental amalgam were important contributors to mercury exposure. Such finding is alarming and priority for further studies are, urgently, needed.

Cadmium and mercury levels in Saudi women and its possible relationship with hypertension.

The association between elevated blood pressure and blood cadmium and mercury levels was examined (2001-2002) in 185 Saudi women previously selected for a case-control study of lead and hypertension risk. Blood pressure was measured twice according to the World Health Organization recommendations. Cadmium and mercury were determined with graphite furnace and hydride system-atomic absorption spectrometry, respectively. Mean blood cadmium concentrations were 0.874 +/- 0.995 microg/L in hypertensive and 0.785 +/- 0.665 microg/L in controls. While blood mercury concentrations for hypertensives and controls were 3.506 +/- 3.617 microg/L and 3.687 +/- 3.186 microg/L, respectively. Participants were classified according to the median of blood cadmium and mercury levels. After adjustment for potentially confounding variables, the final logistic regression analyses revealed that women with blood cadmium > or = 0.627 microg/L were 3.934 times were more likely to be hypertensive than those with blood cadmium levels < 0.627 microg/L, although this was marginally significant (p = 0.098). This was likely the result of the small number of subjects, resulting in the weak power to detect a strong significant difference between hypertensives and control cases. On the other hand, the final regression model showed no association between hypertension and mercury. However, this finding should not be conclusive because of the inappropriate choice of the biomarker indicator. Nevertheless, our study supports the hypothesis that exposure to cadmium might increase the risk of hypertension.

Is lead considered as a risk factor for high blood pressure during menopause period among Saudi women?

This case-control study was designed to examine the association between blood lead levels and high blood pressure in a restricted subpopulation, Saudi women who were 45-93-year old, during or after menopausal period and not occupationally exposed to lead. Blood lead levels were assessed in 100 women with hypertension and 85 control subjects. Lead concentrations were measured in the whole blood using flameless atomic absorption spectrophotometry. Blood pressure measurements were performed according to the World Health Organization recommendations. Results revealed that the mean blood lead levels for hypertensive were 47.52+/-39.26 and 45.59+/-28.55 microg/l for controls. Participants were classified according to the median of blood lead levels in order to compute odds ratios. After controlling a number of potential confounding variables, the multiple logistic regression analysis revealed that women with blood lead levels of > or = 38.6 microg/l were 5.27 times more likely to be hypertensive than those with blood lead levels of < 38.6 microg/l, but of borderline significance (p = 0.06). Although such observation might support the hypothesis that the depletion of lead from bones during menopause increases blood lead levels placing women at increased risk for high blood pressure, there is a need for further studies with larger number of subjects. A number of risk factors, which were suspected to influence blood lead levels, were also investigated. Use of Kohl, duration of its use, osteoporosis disease and intake of calcium supplements were significantly associated with blood lead levels.

Does low mercury containing skin-lightening cream (fair & lovely) affect the kidney, liver, and brain of female mice?

Fair & Lovely is an over-the-counter skin-lightening cream sold widely in Saudi markets. Its mercury content is 0.304+/-0.316 microg/g, in the range of 0.102 to 0.775 microg/g. This study was designed to evaluate its toxic effects on mice. The cream was applied on mice for a period of 1 month at different intervals. Mercury levels were measured in the liver, kidney, and brain tissue samples of a total of 75 adult female CD1 mice by Atomic Absorption Spectrophotometer coupled to a Vapor Generator Accessory. The mean mercury concentrations in the tissues of the treated mice were 0.193+/-0.319 microg/g; whereas for the control group, it was 0.041 microg/g+/-0.041microg/g. While the kidney was found to have the highest mercury content, the brain was found to have the lowest content. Treated mice showed a significant reduction in body weight. Marked histological changes were clearly noted in the kidney and, to a lesser extent, in the brain and liver. These results indicate that although Fair & Lovely mercury content is less than the U.S. Food and Drug Administration (FDA) permissible limits histopathological changes in the brain, kidney, and liver tissues are evidence of its possible toxicity.

Comparison of mercury levels in various tissues of albino and pigmented mice treated with two different brands of mercury skin-lightening creams.

The use of mercury containing skin-lightening creams are becoming increasingly popular among dark-skinned women. The long-term use of certain brands may cause serious health effects over the years. In the present study, we investigated the dermal absorption of mercury and its accumulation in the tissues of albino and pigmented mice treated with two brands of mercury containing skin-lightening creams for a period of one months at different intervals. The mean +/- SD of mercury in the selected brands were: (1) Fair & Lovely (0.304 +/- 0.316 microg/g); and (2) Rose (77513.0 +/- 71063.0 microg/g). Mercury levels were measured in a total of 133 and 144 liver, kidney and brain tissue samples of albino and pigmented mice respectively by the Atomic Absorption Spectrophotometer coupled to Vapour Generator Accessory. In both strains, we found that the mercury concentration in the tissues of mice treated with Rose skin-lightening cream samples was significantly higher than those treated with Fair & Lovely skin lightening cream. Looking at the mercury concentration in the tissue samples with respect to the application of skin lightening creams at different intervals, the highest mercury concentrations were found in the tissues of albino and pigmented mice treated three times a day. On the other hand, the lowest mercury concentrations were found in the tissues of mice treated once a week. Despite the brand of skin-lightening cream that was applied, the study indicated that mercury was readily absorbed through the skin of both albino and pigmented mice as evidenced with its accumulation in the brain, kidney and liver tissues where the kidney had the highest mercury content and brain had the lowest (it P < 0.0001). Significant differences in the mercury levels were observed between the albino and pigmented mice. This emphasizes the protective role of melanin against mercury toxicity. Results of this study stresses the potential harm of these mercury containing skin-lightening creams regardless of their mercury contents especially for women who apply these creams frequently or for extended periods. Permanent nephrological or/and neurological deficits may occur if the damage is severe and diagnosis and treatment are delayed.

Histopathological effects of mercury in skin-lightening cream.

Rose skin-lightening cream with a mercury content of 77,513 +/- 71,063 ppm was selected and applied on mice for a period of 1 month at different intervals. Mercury levels were measured in a total of 58 liver, kidney, and brain tissue samples by atomic absorption spectrophotometer coupled to vapor generator accessory. The mean mercury concentration in the tissues of treated mice was 67,472 +/- 70,181 microg/g in the range of 0.391-288.759 microg/g. Looking at the mercury concentration in the tissue samples with respect to the application of skin lightening creams at different intervals, the highest mercury concentrations were found in the tissues of mice treated 3 times a day (116.806 +/- 83.182 microg/g, ranges 5.989-288.759 microg/g). On the other hand, the lowest mercury concentrations were found in the tissues of mice treated once a week (16.450 +/- 26.168 microg/g, ranges 0.391-95.642 microg/g). Histopathological changes were clearly seen in the brain, kidney, and liver sections of all treated mice. The severity of pathological changes observed in tissues increased with increasing the number of applications. It is evident that repeated application of Rose skin-lightening creams could induce permanent damage to the kidneys, brain, and liver. This study emphasizes the potential toxicity of mercury skin-lighting creams and the importance of discontinuing their manufacture and use.

DDT and its metabolites in breast milk from two regions in Saudi Arabia.

A cross sectional study was designed to measure DDT residues and its metabolites in breast milk samples collected randomly from Saudi lactating mothers living in Al-Ehssa region; which was under leishmania control until 1995, and compare them to samples from mothers living in Riyadh region where no spraying activities was involved. p,p'-DDE, p,p'-DDD and p,p'-DDT residues were measured in 878 breast milk samples by Gas Chromatography/Electron Capture Detector (GC/ECD) and confirmed by Gas Chromatography/Mass Spectrometer Detector (GC/MSD). Variation in the DDT and its metabolites levels were investigated with respect to regional distribution. Wilcoxon rank sum tests showed that the average ranks of p,p'-DDE, p,p'-DDD, p,p'-DDT and sigma p,p'-DDT in lactating mothers from Al-Ehssa region were significantly higher than those living in Riyadh region. These differences supported our hypothesis that the implications of the spraying activities to control vector borne diseases in Al-Ehssa region are obvious. We estimated that 99.2% of infants of lactating mothers living in Al-Ehssa region had sigma p,p'-DDT daily intakes that exceeded 20 micrograms/Kg-day of body weight, the WHO/UNEP Acceptable Daily Intakes for a 5-Kg infant. Exposure of infants to these chemicals through breast-feeding is clearly a public health concern. Because the bulk of literature highlights the adverse health effects of DDT and its metabolites on children and infants, public health polices should enforce the ban of DDT use and advise pregnant and lactating women to avoid DDT containing food or any other type of exposure.

Heavy metal concentrations in the breast milk of Saudi women.

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.