The relation of maternal blood arsenic to anemia during pregnancy.

To clarify the relationship of prenatal arsenic exposure to hemoglobin concentrations and anemia during pregnancy, a longitudinal study was conducted of 364 participants during early pregnancy from October 2006 to March 2011 in Tehran, Iran. Maternal whole blood (taken between 8-12 and 20-24 weeks of gestation, and at delivery) and umbilical cord blood samples were collected for arsenic measurement. The mean concentration of maternal blood arsenic in the first trimester of pregnancy was significantly lower in anemic women compared with non-anemic participants (mean ± SD: 12.4 ± 3.4 versus 14.8 ± 4.0 µg/L, respectively, p < 0.001). Maternal whole blood arsenic levels in the first and third trimesters were significantly (p < 0.05) correlated with hemoglobin concentrations measured throughout gestation (r = 0.312, 0.424, and 0.183). Multiple logistic regression analysis demonstrated that increased maternal blood arsenic levels in the first trimester were significantly negatively associated to anemia during pregnancy (OR = 0.85, CI: 0.77-0.94, p < 0.01). The present study showed that prenatal blood arsenic exposure was not a risk factor for the occurrence of anemia.

Fenitrothion action at the endocannabinoid system leading to spermatotoxicity in Wistar rats.

Organophosphate (OP) compounds as anticholinesterase agents may secondarily act on diverse serine hydrolase targets, revealing unfavorable physiological effects including male reproductive toxicity. The present investigation proposes that fenitrothion (FNT, a major OP compound) acts on the endocannabinoid signaling system in male reproductive organs, thereby leading to spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) in rats. FNT oxon (bioactive metabolite of FNT) preferentially inhibited the fatty acid amide hydrolase (FAAH), an endocannabinoid anandamide (AEA) hydrolase, in the rat cellular membrane preparation from the testis in vitro. Subsequently, male Wistar rats were treated orally with 5 or 10mg/kg FNT for 9 weeks and the subchronic exposure unambiguously deteriorated sperm motility and morphology. The activity-based protein profiling analysis with a phosphonofluoridate fluorescent probe revealed that FAAH was selectively inhibited among the FNT-treated cellular membrane proteome in testis. Intriguingly, testicular AEA (endogenous substrate of FAAH) levels were elevated along with the FAAH inhibition caused by the subchronic exposure. More importantly, linear regression analyses for the FNT-elicited spermatotoxicity reveal a good correlation between the testicular FAAH activity and morphological indices or sperm motility. Accordingly, the present study proposes that the FNT-elicited spermatotoxicity appears to be related to inhibition of FAAH leading to overstimulation of the endocannabinoid signaling system, which plays crucial roles in spermatogenesis and sperm motility acquirement.

Assessment of the reproductive toxicity of inhalation exposure to ethyl tertiary butyl ether in male mice with normal, low active and inactive ALDH2.

No data are available regarding aldehyde dehydrogenase 2 (ALDH2) polymorphisms related to the reproductive toxicity possibly caused by ethyl tertiary butyl ether (ETBE). In this study, two inhalation experiments were performed in Aldh2 knockout (KO), heterogeneous (HT) and wild type (WT) C57BL/6 male mice exposed to ETBE, and the data about general toxicity, testicular histopathology, sperm head numbers, sperm motility and sperm DNA damage were collected. The results showed that the 13-week exposure to 0, 500, 1,750 and 5,000 ppm ETBE significantly decreased sperm motility and increased levels of sperm DNA strand breaks and 8-hydroxy-deoxyguanosine in both WT and KO mice, the effects were found in 1,750 and 5,000 ppm groups of WT mice, and all of the three exposed groups of KO mice compared to the corresponding control; furthermore, ETBE also caused decrease in the relative weights of testes and epididymides, the slight atrophy of seminiferous tubules of testis and reduction in sperm numbers of KO mice exposed to ≥500 ppm. In the experiment of exposure to lower concentrations of ETBE (0, 50, 200 and 500 ppm) for 9 weeks, the remarkable effects of ETBE on sperm head numbers, sperm motility and sperm DNA damage were further observed in KO and HT mice exposed to 200 ppm ETBE, but not in WT mice. Our findings suggested that only exposure to high concentrations of ETBE might result in reproductive toxicity in mice with normal active ALDH2, while low active and inactive ALDH2 enzyme significantly enhanced the ETBE-induced reproductive toxicity in mice, even exposed to low concentrations of ETBE, mainly due to the accumulation of acetaldehyde as a primary metabolite of ETBE.

Differential genotoxic effects of subchronic exposure to ethyl tertiary butyl ether in the livers of Aldh2 knockout and wild-type mice.

Ethyl tertiary butyl ether (ETBE) is used as an additive to gasoline to reduce carbon monoxide emissions in some developed countries. So far, ETBE was not found with positive results in many genotoxic assays. This study is undertaken to investigate the modifying effects of deficiency of aldehyde dehydrogenase 2 (ALDH2) on the toxicity of ETBE in the livers of mice. Eight-week-old wild-type (WT) and Aldh2 knockout (KO) C57BL/6 mice of both sexes were exposed to 0, 500, 1,750, and 5,000 ppm ETBE for 6 h/day with 5 days per weeks for 13 weeks. Histopathology assessments and measurements of genetic effects in the livers were performed. Significantly increased accidences of centrilobular hypertrophy were observed in the livers of WT and KO mice of both sexes in 5,000 ppm group; there was a sex difference in centrilobular hypertrophy between male and female KO mice, with more severe damage in the males. In addition, DNA strand breaks, 8-hydroxyguanine DNA-glycosylase (hOGG1)-modified oxidative base modification, and 8-hydroxydeoxyguanosine as genetic damage endpoints were significantly increased in three exposure groups in KO male mice, while these genotoxic effects were only found in 5,000 ppm group of KO female mice. In WT mice, significant DNA damage was seen in 5,000 ppm group of male mice, but not in females. Thus, sex differences in DNA damage were found not only in KO mice, but also in WT mice. These results suggest that ALDH2 polymorphisms and sex should be taken into considerations in predicting human health effects of ETBE exposure.

Prenatal blood levels of some toxic metals and the risk of spontaneous abortion.

High-level toxic metal exposure has become rare in the recent years. Although, it has not known whether relatively lower exposure may adversely affect human reproductive system. Spontaneous abortion (SA) is a serious reproductive problem, which, in many cases, the cause(s) is not clearly understood. To assess the relationship between prenatal blood level of metals and SA risk, we compared blood concentration of some heavy metals in samples taken from mothers recruited in Tehran Environment and Neurodevelopmental Defects (TEND) study conducted on apparently healthy pregnant women in Tehran, Iran who subsequently experienced spontaneous abortion with mothers who their pregnancy ended to live births. During early gestation, 206 women were enrolled to the survey and followed up till fetal abortion or baby deliveries occur. Blood metal concentrations were measured using an inductively coupled plasma mass spectrometer. The mean blood levels of lead, antimony, and nickel were higher in SA than ongoing pregnancy; however, this difference was not statistically significant. When adjusted for covariates, the logistic regression analysis showed significant association between maternal age and the risk of SA in all models. Among toxic metals only antimony had a noticeable positive relation with the risk of SA (OR: 1.65, 95% CI:1.08-2.52, P value: 0.02). Pearson's correlation coefficient showed significant (P < 0.05) positive correlations among prenatal blood metals levels, except for nickel. Although the present study failed to provide strong evidence for the effects of toxic metals on the occurrence of SA at the relatively low-levels, these metals should be avoided in women who plan pregnancy and/or during the early stages of gestation to prevent the chance of adverse effects.

Hair Metal Levels and Childhood Weight Gain.

BACKGROUND: Exposure to toxic metals remains a public health problem with lifelong impacts on childhood growth and development. We aimed to investigate metals effects on preschool children's anthropometric variables. METHODS: The study was conducted in Tehran, Iran, from Jul 2013 to Mar 2016. We measured scalp hair metal concentrations (lead, cadmium, arsenic, zinc, manganese, and cobalt), using inductively coupled plasma mass spectrometry, in 207 preschool children's (36 to 72 months old). RESULTS: A significant negative correlation between children's hair lead levels and children's weight was found (r= -0.178, P<0.05). Linear regression analysis confirmed the relationship when adjusted for the confounders, including children's age, sex, height, family income, and maternal education (ß= -0.191; t= -3.426, P< 0.01). The ANOVA analysis showed a significant (P<0.01) difference between hair lead level and children's weight-for-age percentiles. Totally and separately, in almost all weight percentiles, hair lead levels were higher in girls than boys. CONCLUSION: The present study on Iranian children showed the current levels of lead exposure might negatively influence on children growth, with higher risk for girls than boys.

Biphasic adverse effect of titanium nanoparticles on testicular function in mice.

The male reproductive system is being recognized as toxic targets of nanoparticles including titanium dioxide nanoparticles (TiNP). Most of these reports are, however, obtained from the results of long-term exposure of TiNP. In this study, we diversely examined the acute effects of TiNP on the male reproductive system. Male C57BL/6J mice were administered a single intravenous injection of TiNP (10, 50 mg/kg), and were sacrificed at 1, 3, and 9 days post-injection. Testicular functions (estimated by sperm motility and sperm number) were measured via computer-assisted sperm analysis (CASA). Results indicated that sperm motility was significantly reduced from 1 day following TiNP injection (in both dose), and this reduction persisted up to 9 days post-TiNP injection (10 mg/kg injection group). Interestingly, we observed no significant decrease in sperm numbers in both the testis and the cauda epididymis in either treatment groups during the course of the experiment. Therefore, we hypothesized that TiNP may target the mature spermatozoa. In addition, sperm suspensions directly incubated with TiNP showed reduced sperm motility, [3H]-thymidine incorporation, and ATP level. Our results indicated that TiNP possesses "biphasic effects"; the obstacles to mature sperms (short term effect) in addition to the impairment in testis (long-term effect).

Lethal chronotoxicity induced by seven metal compounds in mice.

The aim of the present study is to investigate the "chronotoxicity" of seven metal compounds (Hg, Pb, Ni, Cr, Cu, Zn, or Fe) by assessing how their toxicity varies with circadian periodicity. Male ICR mice were injected with each metal compound intraperitoneally at 6 different time points over the course of a day (zeitgeber time [ZT]: ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22). Mortality was then monitored until 14 days after the injection. Our investigation demonstrated that mice were tolerant against Ni toxicity during dark phase, on the other hand, they were tolerant against Cr toxicity during light phase. The chronotoxicity of Hg and Pb seemed to be biphasic. Further, mice were susceptible to toxicities against Cu and Zn in the time zone during which light and dark were reversed. Interestingly, no significant differences were observed for Fe exposure at any time of the day. Our results propose that the chronotoxicology may provide valuable information regarding the importance of injection timing for not only toxicity evaluation tests but also the reproducibility of animal experiments. Furthermore, our data suggests that chronotoxicology may be an important consideration when evaluating the quality of risk assessments for night shift workers who may be exposed to toxic substances at various times of the day.

Prenatal mercury exposure and birth weight.

Adverse effects of prenatal mercury exposure on pregnancy outcomes remain a public health concern. We assessed the relationship between prenatal mercury exposure and newborn anthropometric characteristics in 334 mother-child pairs from the early stages of pregnancy to delivery in Tokyo, Japan, between December 2010 and October 2012. We found a negative correlation between blood mercury levels during the first and second trimesters of gestation and birth weight (r = -0.134 and -0.119, respectively; p < 0.05). Multiple linear regression analysis confirmed the relationship between first-trimester maternal blood mercury levels and birth weight when adjusted for independent variables (ß = -0.170, t = -2.762; p = 0.006). Mean mercury levels in umbilical cord blood were twice as high as maternal blood levels (10.15 ±â€¯7.74 and 4.97 ±â€¯3.25 µg/L, respectively; r = 0.974, p < 0.001). Our findings suggest that pregnant women and women of reproductive age should avoid mercury exposure, even at low levels, because of its potentially adverse effects on fetal development.

Epididymal phospholipidosis is a possible mechanism for spermatotoxicity induced by the organophosphorus insecticide fenitrothion in rats.

Fenitrothion (FNT) is used worldwide in agricultural and public health settings. Spermatogenesis is a toxicological target of FNT under high-dose exposure. Although anti-androgenic action is postulated to be the mechanism associated with this toxicity, few studies have examined histopathology of androgen-dependent male accessory sex organs. The present study aimed to reveal the effects of FNT on the accessory organs of rats exhibiting spermatotoxicity in the absence of testicular histopathological changes. Furthermore, a possible novel molecular target was clarified. Male Wistar rats were orally administered 5 or 10 mg/kg FNT or its major metabolite 3-methyl-4-nitrophenol (MNP), or vehicle only, 4 days per week for 9 weeks. Then the epididymis, prostate, and seminal vesicles were collected. FNT and MNP did not show anti-androgenic effects but FNT induced cytoplasmic vacuolation in the epithelial cells of epididymal ducts and hyperplasia of mucosal folds/epithelial papillomatosis in seminal vesicles. FNT and MNP induced epididymal phospholipidosis, which was presumably caused by inhibition of epididymal secreted phospholipase A2 (sPLA2). Percentages of morphologically normal sperm and immature sperm were significantly predicted from both epididymal sPLA2 and phospholipid levels and from epididymal sPLA2, respectively. These results suggest that epididymal phospholipidosis plays an important role in FNT-induced spermatotoxicity. Anti-androgenic actions were not observed.

Reproductive toxicity of ethylene glycol monoethyl ether in Aldh2 knockout mice.

Ethylene glycol monoethyl ether (EGEE) can cause damage to testes and sperm, and its metabolites are believed to play an important role in its toxicity. Aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of this chemical. To investigate whether and how the enzyme affects the toxicity of EGEE, we conducted experiments comparing Aldh2 knockout mice with wild-type mice. Administration of EGEE at 100 and 600 mg/kg/day for one week did not induce any significant change in the weight and body weight ratios of testes, prostate and epididymides in either Aldh2 knockout or wild-type mice. However, motion of sperm from the spermaduct, as analyzed with a Hamilton-Thorne Sperm analyzer, was slightly decreased in the low dose group, and significantly lower in the high dose group; and the percentage of progressive sperm was also reduced in the two EGEE groups. This effect of EGEE treatment was observed in the wild-type, but not in the Aldh2 knockout mice. Sperm motion from the cauda epididymides was not affected. On the other hand, the concentration of ethoxyacetic acid, a metabolite of EGEE, in 24 h pooled urine of EGEE-treated Aldh2 knockout mice was not significantly lower than that of the wild-type mice on most days of urine sampling. These results suggest that inactivation of the ALDH2 enzyme due to gene mutation may be linked to differences in the susceptibility to EGEE-induced sperm toxicity.

High sensitivity of testicular function to titanium nanoparticles.

Titanium dioxide nanoparticles (TiNPs) present toxicity in organs such as the liver, lung, and intestine. The testis has also been reported as a target organ of TiNPs. We recently reported that TiNPs had no genotoxic effect in the liver and bone marrow, while showing clear testicular dysfunction. In this paper, therefore, we systematically compared the sensitivity of hepatic function using biochemical markers and testicular function against TiNPs. Male C57BL/6J mice were injected intravenously with TiNPs (Aeroxide-P25, at doses of 0.1, 1, 2, and 10 mg/kg body weight) once per week for 4 consecutive weeks. Mice were sacrificed three days after the last injection. Body weights, liver weights, and testicular-related organ weights were not found to be changed by TiNP treatment. Moreover, TiNPs caused no hepatic damage, as evaluated by alanine aminotransferase and aspartate aminotransferase indexes. The testicular function, however, was clearly impaired by TiNP treatment; reduction in two sperm motion parameters (motile percent and progressive percent) and sperm numbers in cauda epididymides was seen. We observed Ti accumulation in the liver but not in the testis, as well as no change in plasma levels of sex hormones related to spermatogenesis. Our findings indicate that the testis is highly sensitive to TiNPs, as compared to the liver. We believe that, when considering the biological effects of TiNPs, testicular function (especially motility ability) may be a sensitive indicator.

Effects of Hair Metals on Body Weight in Iranian Children Aged 20 to 36 Months.

BACKGROUND: Although the level of exposure to many toxic metals decreased recently, the adverse effects of these metals on children's growth and development remain a serious public health issue. METHODS: The present study was conducted in three teaching hospitals affiliated with Tehran University of Medical Sciences (Tehran, Iran) from Sep 2012 to Mar 2013. To study the relationship between metals and childhood growth, concentrations of zinc and several potentially toxic metals (lead, cadmium, antimony, cobalt, and molybdenum) were measured in scalp hair for 174 children, aged 20 to 36 months. RESULTS: The hair concentrations of cobalt were significantly (P<0.05) higher in children at the lower percentile of weight than in higher-weight children (0.026 ± 0.04 vs. 0.015 ± 0.01 µg/g, respectively). Hair contents of lead, cobalt, and antimony were significantly higher (P<0.05) in girls than in boys (8.08 ± 8.7 vs. 4.92 ± 5.6 µg/g for lead, 0.026 ± 0.03 vs. 0.16 ± 0.02 µg/g for cobalt, and 0.188 ± 0.29 vs. 0.102 ± 0.12 µg/g for antimony). There were also significant correlations between lead and other metals in the children's hair. CONCLUSION: Gender may play a significant role in absorption and/or accumulation of metals. It should be considered when we study metal toxicity in children.

Chronotoxicity of bromobenzene-induced hepatic injury in mice.

The aim of the present study is to investigate whether or not bromobenzene (BB) toxicity varies with circadian periodicity. Seven-week-old male ICR mice were injected with 900 mg/kg (5.73 mmol/kg) BB intraperitoneally at 4 different time points of a day (zeitgeber time [ZT]: ZT0, ZT6, ZT12, and ZT18). Mortality was then monitored for 7 days after injection. Interestingly, mice were sensitive to BB acute toxicity at ZT6 while tolerant at ZT18. Moreover, in mice that were given a non-lethal dose of BB (540 mg (3.44 mmol)/kg), levels of alanine aminotransferase and aspartate aminotransferase, used as markers of hepatic injury, markedly increased in response to injection at ZT6, but did not increase significantly in response to injection at ZT18. In contrast, the markers of renal injury (creatinine and blood urea nitrogen), showed no significant difference in response to the two injection times. To further investigate this extreme circadian variation, we examined hepatic and renal lipid peroxidation levels, and conducted histopathological studies. Similar to our observation with alanine aminotransferase and creatinine, hepatic lipid peroxidation and histopathological changes were more pronounced than renal changes, and showed circadian variation. Our present investigation demonstrated that BB-induced mortality had clear circadian variation, and suggested that hepatic injury was one of the important factors for determination of this variation.

Multidirectional analyses of hepatic chronotoxicity induced by cadmium in mice.

The expression levels or activities of biological defense factors can fluctuate daily following biological rhythms. We have focused on the relationship between injection timing and the degree of toxicity of cadmium (Cd) to promote the concept of "chronotoxicology," which introduces chronobiology to the field of toxicology. Our previous studies have clearly indicated that Cd may be subject to chronotoxicity. In this report, to confirm the character of the Cd-induced chronotoxicity, we performed multidirectional examinations. Male C57BL/6J mice that received a single intraperitoneal injection of CdCl2 at ZT6 showed drastic hepatic injury estimated by histopathological analyses, i.e., nuclear condensations, fatty degenerations, and hemorrhages, but showed no injury when injected at ZT18. This difference was supported by several biochemical analyses that were indicators of hepatic injury (levels of alanine aminotransferase, aspartate aminotransferase, and malondialdehyde). The chronotoxicity of Cd was also observed in multiple strains (ICR and Balb/c), in a different injection route (subcutaneous), and in multiple injections (5 injections). Based on these results, we propose that chronotoxicology may provide important information not only for toxicology but also for occupational health, i.e., the importance of injection timing for toxicity evaluation tests, the reproducibility of animal experiments, and the improvement in the quality of risk assessments for night shift workers who may be exposed to toxic substances at various times of the day.

Inhibitory effect of ethylene glycol monoethyl ether on rat sperm motion.

Ethylene glycol monoethyl ether (EGEE) is known to have testicular toxicity. To elucidate whether EGEE has any effect on sperm motion, especially in the case of short time exposure, we conducted a series of in vivo experiments with rats, as well as an in vitro study with rat sperm. Sperm from cauda epididymides and spermaducts was analyzed for the change in motion with a Hamilton-Thorne Sperm analyzer. Administration of EGEE at 600 mg/kg/d for five weeks significantly decreased total and progressive motility of sperm to 15-30% of controls, in both the cauda epididymis and the spermaduct. The time-course experiment using a single dose of 1,000 mg/kg showed that damage to sperm motion was evident at 12-24 h after EGEE administration. Addition of EGEE to the medium of sperm had no effect on its motion, but the metabolite ethoxyacetic acid showed a significant inhibitory effect. These results suggest that besides its toxicity to spermatogenesis, the metabolite of EGEE may also directly affect the motion of mature sperm.

Increased prenatal blood manganese may induce gestational blood pressure.

OBJECTIVE: Pregnancy hypertension is the most common gestational complication and poses a critical risk for mother and fetus. Whether environmental factors may play an important role in disease occurrence is not fully determined. METHODS: To investigate the effects of prenatal manganese (Mn) exposure on gestational blood pressure, 386 women were examined. RESULTS: Early pregnancy blood Mn was significantly (p < 0.05) correlated with blood pressure through gestation. A significant association between odds of pre-hypertension with blood Mn was shown (OR:1.150, 95% CI:1.052-1.258). CONCLUSION: The current study results might suggest the blood Mn level during early stage of pregnancy as a potential risk factor for increasing the risk of gestational blood pressure.

A comprehensive evaluation of the testicular toxicity of dichlorvos in Wistar rats.

Assessments of the reproductive toxicity of organophosphorus insecticides are important public health issues. This study aimed at defining the testicular toxicity of dichlorvos (DDVP) since this toxicity was suspected by our previous survey on pesticide sprayers and in some earlier publications during the 1970s. Ten-week-old Wistar rats were divided into four groups (n=8 or 9) and were injected subcutaneously with DDVP (0, 1, 2 or 4 mg/kg) 6 days a week for 9 weeks. After that period, erythrocyte cholinesterase (ChE) activities decreased dose-dependently, showing 44-55% inhibition among the treated groups. No significant difference was observed in the reproductive organ weights in any treated groups compared with the control group. Sperm motility decreased slightly but significantly in the 1 and 4 mg/kg groups, and significant regressions were observed between sperm motility and both blood ChE activity and urinary concentration of dimethyl phosphate (DMP), a urine metabolite of DDVP. However, sperm counts and sperm morphology in the cauda epididymidis, plasma testosterone concentrations, and histopathology in the testes in all the treated groups were not significantly different from those of the control group. Since only the sperm motility deteriorated by DDVP exposure at doses inducing marked inhibition of cholinesterase activities in the rats, it was suggested that the risk of testicular dysfunction posed to occupationally exposed humans would be small in terms of the effect of DDVP exposure alone. This conclusion was also supported by an estimate of the decrease in human sperm motility based on the urinary DMP concentrations observed in actual occupational settings.

Comparative investigation of several sperm analysis methods for evaluation of spermatotoxicity of industrial chemical: 2-bromopropane as an example.

Reproductive toxicity of 2-bromopropane (2BP), a substitute for ozone layer-depleting chloro-fluorocarbon, was found among the workers in an electronics factory in Korea in 1995. Furthermore the importance of testicular toxicity has been realized since the problem of endocrine disruptors arose all over the world, but manual methods must rely on subjective assessment. Recently, computer-assisted sperm analysis (CASA) was proposed but this system requires vast investment. We then investigated the applicability of the MTT method with a microplate and sperm quality analyzer (SQA) as simple, rapid, and economic instrumental methods for the examination of sperm quality in rats, comparing it with the manual microscopic method and CASA. Epididymal fluid derived from male F344/N Slc (Fischer) rats intraperitoneally injected with 2BP in the dose range of 125-1,000 mg/kg/d twice a week (total 8 times) were examined by these methods as a model experiment. Sperm count measured by the manual method and CASA in the epididymal fluid, absorbance by the MTT method and sperm motility index value by the SQA method were significantly lower in the 2BP 1,000 mg/kg administered group than in the control group. This result suggests that the MTT method can detect oligospermia. With the microplate and microplate reader, the efficiency of detection becomes much better. Sperm analyses by the MTT method with the microplate reader and the SQA method are available for reproductive toxicity study in rats.

Low level prenatal blood lead adversely affects early childhood mental development.

The effect of prenatal lead exposure on child development has been a topic of public health concern for decades. To estimate prenatal lead exposure effects on early childhood development, maternal blood (n = 364) and umbilical cord blood (n = 224) samples were collected during pregnancy and at delivery. Mental development was assessed using the Harold Ireton Early Child Development Inventory from 174 children. Maternal whole blood lead levels in the first trimester were significantly higher in children with developmental scores <20% than in those with normal scores (mean ± standard deviation: 6.3 ± 1.9 vs 4.0 ± 2.4 µg/dL, respectively, P = .01). Maternal blood lead levels in the first trimester were also inversely associated with the development scores (r = -0.155, P = .041). Logistic regression analysis showed a significant relationship between increasing maternal blood lead levels in the first trimester with low development scores (odds ratio = 1.74, 95% confidence interval = 1.18-2.57, P = .005). The findings of the present study showed a relatively low level of prenatal lead exposure (mean < 6.5 µg/dL) associated with lower developmental scores in early childhood.