Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol

OBJECTIVES: The study examined acute neurobehavioral effects provoked by controlled exposure to 1-octanol and isopropanol among male volunteers. METHODS: In a 29-m3 exposure laboratory, 24 male students (mean age 25.8 years) were exposed to 1-octanol and isopropanol. Each substance was used in two concentrations (0.1 and 6.4 ppm for 1-octanol; 34.9 and 189.9 ppm for isopropanol:). In a crossover design, each subject was exposed for 4 hours to the conditions. Twelve subjects reported enhanced chemical sensitivity; the other 12 were age-matched controls. At the onset and end of the exposures neurobehavioral tests were administered and symptoms were rated. RESULTS: At the end of the high and low isopropanol exposures the tiredness ratings were elevated, but no dose-dependence could be confirmed. For both substances and concentrations, the annoyance ratings increased during the exposure, but only for isopropanol did the increase show a dose-response relation. The subjects reported olfactory symptoms during the exposure to the high isopropanol and both 1-octanol concentrations. Isopropanol provoked no sensory irritation, whereas high 1-octanol exposure slightly enhanced it. Only among the subjects with enhanced chemical sensitivity were both 1-octanol concentrations associated with a stronger increase in annoyance, and lower detection rates were observed in a divided attention task. CONCLUSIONS: Previous studies reporting no neurobehavioral effects for isopropanol (up to 400 ppm) were confirmed. The results obtained for 1-octanol lacked dose-dependency, and their evaluation, is difficult. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task.     

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls

Lead and polychlorinated biphenyls (PCBs) both cause a reduction of intelligence quotient and behavioral abnormalities in exposed children that have features in common with attention deficit hyperactivity disorder. We have used rats as a model to study the effects of both perinatal and acute exposure to lead or PCBs in an effort to compare and understand the mechanisms of these nervous system decrements. Long-term potentiation (LTP) is an electrophysiologic measurement that correlates well with cognitive ability. We have determined the effects of chronic perinatal exposure to lead or PCB 153 as well as acute application of these substances to isolated brain slices, with recordings in two areas of the hippocampus, CA1 and CA3. Both substances, whether chronically or acutely applied, significantly reduced LTP in CA1 in animals at age 30 and 60 days. In CA3, they reduced LTP in 30-day animals but potentiated it in 60-day animals. Although neither lead nor PCB 153 alters baseline synaptic transmission at low stimulus strengths, at higher levels they induce changes in the same direction as those of LTP. These results show surprisingly similar actions of these quite different chemicals, and the similarity of effects on chronic and acute application indicates that effects are both pharmacologic and developmental. Behavioral studies of rats exposed to PCBs from contaminated fish show hyperactivity, impulsiveness, and increased frustration relative to unexposed controls. These results demonstrate that lead and PCBs have similar effects on synaptic plasticity and behavior and suggest that the compounds may act through a common mechanism.     

Neurobehavioral effects of acute and chronic mixed-solvent exposure in the screen printing industry

This 2-year prospective study examined the neurobehavioral effects of acute and chronic exposure to mixed solvents in workers in a screen printing business. A total of 30 subjects participated in the study in two field testings over a 12 month period. Each subject completed a detailed medical and occupational questionnaire, had a neurological examination, and underwent a battery of neuropsychological tests. Industrial hygiene investigation identified the following chemical exposures as present: toluene, methyl ethyl ketone, mineral spirits, β-ether, methylene chloride, and acetic acid. Different departments and jobs had varying degrees of exposure to these chemicals, the highest exposures being in the ink mix area and the screen washroom area. However, all exposure levels were below recommended threshold limit values. Persons categorized as having higher acute exposure demonstrated significantly impaired test performance on tasks involving manual dexterity, visual memory, and mood. Those with higher chronic exposure demonstrated significantly poorer performance on visual memory tasks and mood. Results suggest that the mixed solvents used in the screen printing industy have an effect on central nervous system functioning in the absence of obvious clinical disease.     

Neurobehavioral effects of exposure to trichloroethylene through a municipal water supply

We studied a population-based sample of 143 residents of a community in which the municipal water supply had been contaminated with trichloroethylene (TCE) and related chemicals from several adjacent hazardous waste sites between 1981 and 1986. A hydraulic simulation model was used in conjunction with a geographic information system (GIS) to estimate residential water supply exposures to TCE; 80% of the participants had potential TCE exposure exceeding the maximum contaminant level (5 ppb). The Neurobehavioral Core Test Battery (NCTB), tests of visual contrast sensitivity, and the profile of mood states (POMS) were administered approximately 6 years following peak concentrations of TCE in municipal drinking water. Multivariate analysis of variance adjusted for potential confounders was used to compare mean test scores of residents classified by estimated TCE exposure (< or =5, >5-10, >10-15, >15 ppb). TCE exposure >15 ppb was associated with poorer performance on the digit symbol, contrast sensitivity C test, and contrast sensitivity D test and higher mean scores for confusion, depression, and tension. We found evidence of a strong interaction between exposure to TCE and alcohol consumption; the associations for the NCTB and POMS among persons in the high-exposure group who also consumed alcohol were stronger and were statistically significant for the Benton, digit symbol, digit span, and simple reaction time tests, as well as for confusion, depression, and tension. This study adds to the evidence that long-term exposure to low concentrations of TCE is associated with neurobehavioral deficits and demonstrates the usefulness of GIS-based modeling in exposure assessment.     

Neurobehavioral function and low-level metal exposure in adolescents

An excessive metal exposure is harmful to the brain. However, many aspects of metal neurotoxicity remain unclear including the magnitude of the low-level exposure effects and the level of exposure that can be assumed safe. The aim of our study was to investigate the association between a low-level metal exposure and three neurobehavioral domains (sustained attention, short-term memory, and manual motor speed). We measured Cd, Cu, Mn, Pb, and Tl in blood, Cd, Ni, and toxicologically relevant As in urine and methyl Hg in hair in 606 adolescents between 13.6 and 17 years of age. A two-fold increase in blood Cu was associated with a 0.37 standard deviations decrease in sustained attention (95% CI: −0.67 to −0.07, p = 0.02) and 0.39 standard deviations decrease in short-term memory (95% CI: −0.70 to −0.07, p = 0.02), accounting for gender, age, smoking, passive smoking, household income per capita, occupation of the parents, and education level of the mother. None of the other metals was significantly associated with the neurobehavioral domains that were measured. The observed associations between blood Cu and neurobehavioral performance are in line with recent studies in elderly. However, the relevance of our results for public health remains to be elucidated.     

PCB metabolism in rats following prolonged exposure to Aroclor 1242 and Aroclor 1016

Summary Several mono- and dihydroxy metabolites of ditri, and tetrachlorobiphenyl have been identified in the urine of rats fed prolonged diets of Aroclor 1016 or Aroclor 1242. Combined gas chromatography-mass spectrometry was used for characterization of the metabolic products.     

The effects of PCB exposure and fish consumption on endogenous hormones.

Previous studies have suggested that exposure to polychlorinated biphenyls (PCBs) may alter thyroid function, but data on effects of PCB exposure on other endogenous hormones has been lacking. The current study is ancillary to a larger investigation of the effects of Great Lakes fish consumption on PCBs and reproductive function. In the current study we examine associations of PCBs, 1,1-bis (4-chlorophenyl)-2,2-dichloroethene (DDE), and fish consumption with thyroid and steroid hormones in 178 men and PCBs, DDE, and fish consumption with thyroid hormones in 51 women from the original study. Serum PCB level and consumption of Great Lakes fish are associated with significantly lower levels of thyroxine (T(4)) and free thyroxine index (FTI) in women and with significantly lower levels of T(4) in men. Fish consumption, but not PCB level, is significantly and inversely associated with triiodothyronine (T(3)) in men. Results for thyroid-stimulating hormone (TSH) are inconsistent. Among men, there are significant inverse associations of both PCB and fish consumption with sex hormone-binding globulin (SHBG)-bound testosterone, but no association with SHBG or free testosterone. There are no significant overall associations of PCB, DDE, or fish consumption with estrone sulfate, follicle-stimulating hormone, luteinizing hormone, or dehydroepiandrosterone sulfate. The results of this study are consistent with previous studies showing effects of fish consumption and PCB exposure on thyroid hormones and suggest that PCBs may also decrease steroid binding to SHBG. Elucidation of specific mechanisms must await future investigations.     

围产期暴露任基酚对子代大鼠脂肪组织形成影响

目的探讨围产期暴露壬基酚对子代大鼠脂肪组织的形成以及对大鼠脂肪组织中ERα表达的影响。方法雌性大鼠从妊娠期(GD)第6 d至分娩后21 d分别给予壬基酚(5、25、125μg/kg),另设一对照组,每天灌胃1次。子代出生后(PND)21 d时,处死部分幼鼠,收集血清;剩余部分幼鼠按性别分笼喂养,给予普通饲料至实验结束。23周后,断头处死,收集血液,并迅速取出肾周和性腺周围脂肪组织。结果与对照组[雄性(384±43)g、雌性(231±8)g]比较,5、25、125μg/kg壬基酚组子代大鼠体重[雄性分别为(453±51)、(475±57)、(509±29)g,雌性分别为(260±13)、(260±12)、(284±3)g]均升高(均P<0.05);与对照组比较,各计量壬基酚组子代大鼠血清中瘦素的水平均升高(均P<0.05);与对照组[雄性(6 307±312)μm2、雌性(5 915±287)μm2]比较,5、25、125μg/kg壬基酚组子代大鼠脂肪细胞面积[雄性分别为(10 142±9 209)、(17 465±9 830)、(33 854±2 620)μm2,雌性分别为(10 100±9 095)、(15 134±965)、(31 280±4 654)μm2]均增加(均P<0.05);与对照组比较,各剂量任基酚组子代大鼠脂肪分化和增殖基因表达均增加,子代大鼠脂肪组织中ERα基因和蛋白表达水平均降低(均P<0.05)。结论围产期暴露壬基酚可以导致子代大鼠肥胖,脂肪组织中ERα基因和蛋白表达的降低可能是壬基酚的作用机制之一。     

Neurobehavioral effects of long-term occupational exposure to organic solvents: two comparable studies.

Two comparable cross-sectional studies were carried out employing the same methodology but involving two separate solvent-exposed populations (N = 90, N = 144). In each study, solvent-exposed workers were compared with age-matched controls on tests selected from the Neurobehavioral Evaluation System and on standardized questionnaire measures of symptomatology and psychiatric state. A similar pattern of results was obtained in the two studies indicating a significant effect on cognitive functioning, after controlling for confounding variables, occurring in those with more than 30 years of exposure. A more specific effect on learning processes was observed in those with more than 10 years of exposure. There were no indications in either study of a solvent-related increase in psychiatric symptoms.     

Comparing the effects of perinatal and later childhood lead exposure on neuropsychological outcome

Blood lead values (PbB) from cord blood and maternal samples as well as present PbB from venous blood samples were available for 114 six- to seven-year-old children living in or near the city of Nordenham (FRG). These children represented 30% of all children born between July 1975 and August 1976 in the district hospital (N = 383). The range of cord blood PbB was 4-31 micrograms/100 ml (mean = 8.2 micrograms/100 ml) and of maternal PbB was 4-30 micrograms/100 ml (mean = 9.3 micrograms/100 ml), whereas the range for present PbB was 3.9-22.8 micrograms/100 ml (mean = 8.2 micrograms/100 ml). The degree of correlation between maternal and cord blood PbB was 0.79, despite the poor technical quality of many cord blood samples as compared to maternal blood samples (less coagulation). These children were given a battery of neurophysiological and neuropsychological tests. The present report is restricted to psychological performance measures. The test battery covered intelligence (reduced Wechsler Intelligence Scale for Children), visual-motor performance (Bender Test, GFT), serial reaction performance (Wiener Reaction Device), and cued as well as choice reaction times. After correction for confounding by means of stepwise multiple-regression analysis, few significant associations between blood lead levels and performance deficit occurred. In general the degree of association was somewhat stronger for present PbB than for perinatal PbB: With increasing present PbB there was a borderline drop of performance IQ (P less than 0.1), as well as a significant disruption of serial reactions, which was more pronounced for the difficult (P less than 0.01) than for the easier version of the Wiener Device (P less than 0.05). A similar but less pronounced pattern of associations was observed for maternal PbB but not for cord blood PbB. Some influence of perinatal lead exposure on later performance can, thus, still be detected if, in addition to cord blood PbB, maternal PbB is taken into account as well.     

Neurobehavioral development in children with potential exposure to pesticides

BACKGROUND: Children may be at higher risk than adults from pesticide exposure, due to their rapidly developing physiology, unique behavioral patterns, and interactions with the physical environment. This preliminary study conducted in Ecuador examines the association between household and environmental risk factors for pesticide exposure and neurobehavioral development. METHODS: We collected data over 6 months in the rural highland region of Cayambe, Ecuador (2003-2004). Children age 24-61 months residing in 3 communities were assessed with the Ages and Stages Questionnaire and the Visual Motor Integration Test. We gathered information on maternal health and work characteristics, the home and community environment, and child characteristics. Growth measurements and a hemoglobin finger-prick blood test were obtained. Multiple linear regression analyses were conducted. RESULTS: Current maternal employment in the flower industry was associated with better developmental scores. Longer hours playing outdoors were associated with lower gross and fine motor and problem solving skills. Children who played with irrigation water scored lower on fine motor skills (8% decrease; 95% confidence interval = -9.31 to -0.53), problem-solving skills (7% decrease; -8.40 to -0.39), and Visual Motor Integration test scores (3% decrease; -12.00 to 1.08). CONCLUSIONS: These results suggest that certain environmental risk factors for exposure to pesticides may affect child development, with contact with irrigation water of particular concern. However, the relationships between these risk factors and social characteristics are complex, as corporate agriculture may increase risk through pesticide exposure and environmental contamination, while indirectly promoting healthy development by providing health care, relatively higher salaries, and daycare options.     

Neurobehavioral and respiratory symptoms of formaldehyde and xylene exposure in histology technicians

Disturbances of memory, mood, equilibrium, and sleep that occurred simultaneously with headache and indigestion, were experienced more frequently among women working in histology who had daily exposure to formaldehyde, xylene, and toluene than in unexposed female clerical workers working in the same hospitals. Neurobehavioral symptoms were accompanied by irritation of eyes, upper airways, and trachea. Formaldehyde exposure correlated better with neurobehavioral symptoms and with respiratory and mucous membrane symptoms than did exposure to xylene/toluene or to other agents.     

出生前后甲基汞暴露对幼鼠海马和小脑结构的影响

目的评价出生前后低水平甲基汞暴露对幼鼠海马和小脑结构的影响。方法将SD孕鼠随机分为Ⅰ、Ⅱ和Ⅲ组。Ⅰ组为对照组,自由饮用蒸馏水;Ⅱ、Ⅲ组自孕7天至哺乳期末饮水中分别加入0·1和1mg/(kg·d)甲基汞。观察各组幼鼠早期生理发育指标,21天时取其海马和小脑组织观察结构变化情况。结果各组幼鼠无明显形态和早期生理发育指标的异常改变,21日龄时汞暴露组幼鼠体重低于对照组。光镜下Ⅲ组海马和小脑有个别神经细胞固缩改变,海马结构排列紊乱,Ⅱ组无明显病理改变。免疫组化方法分析阳性表达率,海马NFⅢ组和Ⅱ组低于Ⅰ组(F=7·94,P<0·01);海马GFAPⅢ组和Ⅱ组高于Ⅰ组(F=10·10,P<0·01);小脑NFⅢ组小于Ⅰ组和Ⅱ组(F=6·85,P<0·05);小脑GFAPⅢ组大于Ⅰ组和Ⅱ组(F=4·98,P<0·05)。电镜下观察到Ⅱ组和Ⅲ组均有超微结构改变,如神经元核不规则、胞体固缩、线粒体变性、突起溶解等。结论出生前后低水平甲基汞暴露影响了小脑和海马的超微结构和神经细胞表达。     

Neurobehavioral estimation of children with life-long increased lead exposure

A battery of neurobehavioral examinations was carried out on 30 children who were 6-11 yr of age and who had resided near a lead smelter all their lives. Their blood lead levels were 35-60 micrograms/100 ml and erythrocyte protoporphyrin levels were greater than 100 micrograms/100 ml. Neurological examination revealed that they had a significantly higher incidence of pathological findings (e.g., muscle hypotonia, increased tendon reflexes, dysarthria, and dysdiadochokinesia) than children from an unpolluted area who were matched for age, sex, family size, and educational and socioeconomic status of the parents, but who had normal erythrocyte protoporphyrin levels. The children with elevated blood lead levels showed, after assessment by the Oseretsky test, retardation of motor maturation; they also scored higher on the minimal brain damage scale of the Rutter behavioral questionnaire. These differences persisted at a 4-yr follow-up, and their school performance was consistently poorer than that of the controls.     

Effects of perinatal exposure to bisphenol A on sociosexual behavior of female and male rats

Perinatal action of estrogens or aromatizable steroids at the central nervous system level is responsible for brain sexual differentiation. Through early contact with the central nervous system, the estrogenic compound bisphenol A (BPA) could alter the processes affecting sociosexual behavior. To test this hypothesis, we studied agonistic and sexual behavior of adult female and male rats whose mothers were administered BPA (40 microg/kg/day) during pregnancy or lactation. An intruder test revealed in males but not in females an increase in defensive behavior due to BPA. We studied the effect of BPA on sexual behavior by testing sexual orientation and sexual activity. Male sexual orientation toward a stimulus female was not affected by BPA, whereas the sexual activity test revealed a slight impairment of sexual performance due to BPA in terms of latency and frequency of intromissions. In females, BPA produced a small increase in sexual motivation and receptive behavior. In conclusion, BPA administration, both during pregnancy and during lactation, does not masculinize female behavior or potentiate masculinization processes of males. On the contrary, we observed a potentiation of female behavior in females and a depotentiation of male behavior in males.     

Neurotoxic effects of low-level chronic acephate exposure in rats

Rats were administered the organophosphorus insecticide acephate at 1.0 or 10.0 mg/kg.day for 15 weeks. Blood and brain samples were collected at the end of the treatment and analyzed for cholinesterase, acetylcholinesterase, and glutamic acid decarboxylase activities and catecholamine and amino acid levels. No significant inhibition in the activity of brain AChE was noted at doses of 1.0 or 10.0 mg/kg.day. Low levels of acephate exposure (1.0 mg/kg.day), which did not alter plasma cholinesterase or RBC acetylcholinesterase activity levels, resulted in a significant elevation of plasma epinephrine and norepinephrine levels. Decreased GABA, dopamine, and tyrosine levels and glutamic acid decarboxylase activity were observed in brains of these rats. Similar changes occurred in rats exposed to 10 mg of acephate/kg.day; however, plasma cholinesterase and RBC acetylcholinesterase activities were inhibited. These observations suggest that chronic exposure to acephate altered the activity of the noncholinergic system without altering the cholinergic activity, and that low-level chronic exposure to organophosphorous compounds cannot be predicted by measuring the ChE or AChE enzyme activities.     

Behavioral effects of subchronic inorganic manganese exposure in rats

BACKGROUND: Manganese, an essential micronutrient, is a potential neurotoxicant in prolonged overexposure. Parkinson-like syndrome, motor deficit, disturbed psychomotor development are typical signs of neuropathological alterations due to Mn in humans. METHODS: Young adult rats, in three groups of 16 each, received 15 and 59 mg/kg b.w. MnCl(2), (control: distilled water) via gavage for 10 weeks, and were kept for further 12 weeks. Correlation of MnCl(2) exposure to body and organ weights, neurobehavioral effects (spatial memory, exploratory activity, psychomotor performance, pre-pulse inhibition), and histopathological changes (gliosis) was sought. RESULTS: By the end of treatment, Mn accumulated in blood, cortex, hippocampus, and parenchymal tissues. Body and organ weights were reduced in high dose rats. All treated rats showed hypoactivity, decreased memory performance, and diminished sensorimotor reaction. In the dentate gyrus of these, GFAP immunoreactivity increased. During the post-treatment period, body weight of the high dose group remained decreased, locomotor activity returned to control, but the lasting effect of MnCl(2) could be revealed by amphetamine. CONCLUSION: Using complex methodology, new data were obtained regarding the relationship between the long-term effects of MnCl(2) at neuronal and behavioral level.     

围生期接触磺胺二甲嘧啶对子代大鼠甲状腺功能的影响

目的研究围生期母体接触磺胺二甲嘧啶对子代大鼠甲状腺功能的影响。方法受孕母鼠在受孕第7日起至哺乳期结束每天分别给予磺胺二甲嘧啶0、50、100和200mg/kg,HE染色观察20日龄子代大鼠甲状腺的组织病理学变化,并用免疫组织化学染色观察甲状腺内核增殖抗原的表达。结果各染毒剂量组子代大鼠甲状腺滤泡细胞出现不同程度的增生表现,核增殖抗原表达阳性细胞数显著高于对照组(P0.05)。结论磺胺二甲嘧啶可通过母体干扰子代大鼠甲状腺功能。