Review of adverse health effects of odours in field studies.

UNLABELLED: Exposure to environmental odours from industrial and agricultural premises, in addition to inducing annoyance responses in a dose-dependent manner, have been shown to be either directly associated with gastric symptoms as well as general health-related complaints under extreme exposure conditions, or indirectly mediated through odour annoyance under moderate odour exposure conditions. OBJECTIVE: In order to examine the influence of hedonic tone (pleasantness-unpleasantness) and perceived odour strength (intensity) on symptom reporting the results of two pertinent field studies were analysed. METHODS: In the vicinity of six industrial plants (sweets, rusk, textile, seed-oil, fat, cast iron) and eleven livestock operations (poultry, pig, cattle) assessment of odour exposure was done by means of systematic field inspections. Effect assessment was done by means of direct interviews (industrial: N=1456, agricultural: N=1053) using questionnaires covering odour annoyance, symptom reporting and relevant covariates. DATA ANALYSIS: Multiple logistic regression analysis was used to establish dose-response associations between odour frequency, intensity and hedonic tone as independent variables and symptom reporting as dependent variable. RESULTS: Exposure-symptom associations are strongly influenced by hedonic tone, whereas intensity has no additional predictive value. Adding odour annoyance to the regression model shows that symptom reporting is exclusively mediated by annoyance.

Odour intensity and hedonic tone--important parameters to describe odour annoyance to residents?

The Guideline on Odour in Ambient Air has been in use for many years for odour regulation in Germany. The main parameter that the odour regulation authority has to take into account is the odour frequency expressed as odour hours per year. In the guideline, limit values are given for the maximum odour frequency per year. These limit values are based on field investigations in which significant relationships between odour impact and odour annoyance was found. In these investigations, odour intensity did not yield a better description of the degree of annoyance caused to the residents. The hedonic tone was not mentioned. In a new research project finished in 2003, the influence of odour intensity and hedonic tone, in addition to odour frequency, has been assessed. Two installations emitting pleasant odours, two emitting neutral and two emitting unpleasant odours, have been selected. In each case grid field measurements by a panel were carried out, and the annoyance of the residents was assessed using a special questionnaire. The results of this project are: (1) A new method to measure odour intensity and hedonic tone in the field with data record forms was developed and validated. With this method, reliable and reproducible results are obtained. (2) The parameter odour frequency based on the system of "odour hours" is suitable and sufficient to predict the odour annoyance caused by unpleasant/neutral odours. (3) In the case of pleasant odours, hedonic tone has an abundantly clear effect on the dose-response relationship between odour frequency and annoyance. Pleasant odours have a significant lower annoyance potential than unpleasant/neutral odours. (4) The odour intensity has no additional influence on this relationship. If odours are recognisable then they can cause annoyance.

Persistent organochlorine pollutants in human serum of 50-65 years old women in the Flanders Environmental and Health Study (FLEHS). Part 1: Concentrations and regional differences.

In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to assess pollutant concentrations and related health effect biomarkers in humans living in two regions of Flanders. The study was called the 'Flemish Environment and Health Study' (FLEHS). One of the goals was to measure present concentrations of persistent organochlorine pollutants in a Flemish population and to compare values obtained from pooled and individual serum samples. Concentrations of selected organochlorine pesticides, polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were measured by gas chromatography-mass spectrometry. TEQ values were also assessed by Chemical-Activated LUciferase gene eXpression (CALUX) bioassay. The study population consisted of 200 women between 50 and 65 years living in two areas of Flanders, Belgium. Because of the large volumes serum needed for all measurements, the concentrations of organochlorines were measured in 47 pooled serum samples originating from these women. The concentrations of the indicator PCBs (359.8 ng/g fat) and organochlorine pesticides (hexachlorobenzene, p,p'-dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyl-trichloroethane, lindane and pentachlorophenol), were comparable to those found in other European countries. The concentrations of PCDD/PCDFs showed another picture. With a median value of 48 pg WHO-TEQ/g fat, the women had 2-fold higher levels than a comparable age group from Germany examined in 1996. The mean total WHO-TEQ including PCDD/F, non-ortho and mono-ortho PCBs was 72.7 pg WHO-TEQ/g fat, whereas the CALUX-TEQ mean value was only 35.0 pg TEQ/g fat. In order to assess the pooling procedure, indicator PCBs and CALUX-TEQs were measured in all 200 individuals that were integrated in the pools. The measured values were comparable to the pool results: 390.0 ng/g fat and 41.6 pg TEQ/g fat respectively. It was concluded that pooling of serum samples offers the possibility to measure exposure in the whole study population on a more cost-effective way. However, because of statistical power loss and no possibility of confounder adjustment, pooling is not the most effective way to study regional differences.

Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood.

BACKGROUND: There is uncertainty whether environmental levels of exposure to polychlorinated biphenyls (PCBs) adversely affect mental and motor development in early childhood. We aimed to establish whether such an effect is of only prenatal or additional postnatal origin, and if a favourable home environment can counteract this effect. METHODS: Between 1993 and 1995 we recruited 171 healthy mother-infant pairs and prospectively measured psychodevelopment in newborn infants aged 7, 18, 30, and 42 months. We estimated prenatal and perinatal PCB exposure of newborn babies in cord blood and maternal milk. At 42 months we measured postnatal PCB concentrations in serum. At 18 months the quality of the home environment was assessed using the Home Observation for Measurement of the Environment scale. Mental and psychomotor development of the children were assessed using the Bayley Scales of Infant Development until 30 months and the Kaufman Assessment Battery for Children at 42 months. FINDINGS: Negative associations between milk PCB and mental/motor development were reported at all ages, becoming significant from 30 months onwards. Over 30 months, for a PCB increase from 173 (5th percentile) to 679 ng/g lipids in milk (95th percentile) there was a decrease of 8.3 points (95% CI -16.5 to 0.0) in the Bayley Scales of Infant Development mental scores, and a 9.1 point decrease (95% CI -17.2 to -1.02) in the Bayley Scales of Infant Development motor scores. There was also a negative effect of postnatal PCB exposure via breastfeeding at 42 months. Home environment had a positive effect from 30 months onwards (Bayley Scales of Infant Development mental score increase of 9.4 points [95% CI 2.2-16.7]). INTERPRETATION: Prenatal PCB exposure at current European background levels inhibits, and a favourable home environment supports, mental and motor development until 42 months of age. PCB exposure also has an effect postnatally.

Comparison of CALUX-TEQ values with PCB and PCDD/F measurements in human serum of the Flanders Environmental and Health Study (FLEHS).

In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to assess pollutant concentrations and related health effect biomarkers in humans living in two regions of Flanders. The study was called the 'Flemish Environment and Health Study' (FLEHS). Concentrations of selected organochiorine pesticides, polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and flirans (PCDF) were measured by gas chromatography-mass spectrometry in 47 pooled human serum samples originating from 200 individual women between 50 and 65 years living in two Flemish regions. The CALUX (Chemical-Activated Luciferase gene eXpression) bioassay was assessed on the same pools. The correlation between CALUX-TEQ and total TEQ (sum of PCDD/PCDF, non- and mono-ortho PCBs) varied from 0.43 to 0.73 for the rural and urban region, respectively. The mean value for the total TBQ (75 pg WHO-TEQ/g fat) was two times higher than the mean TEQ value determined with the CALUX bioassay (36 pg TEQ/g fat). This shows that the assessment of dioxin-like exposure by these two measurements was different. However, regional differences in concentrations were observed for neither total TEQs, nor CALUX-TEQs. It was concluded that the CALUX can be an alternative screening tool for biomonitoring purposes, especially when the objective is to compare different groups of people (e.g. living in different regions).

Neurotransmitter concentrations and binding at dopamine receptors in rats after maternal exposure to 3,4,3',4'-tetrachlorobiphenyl: the role of reduced thyroid hormone concentrations.

Polychlorinated biphenyls (PCBs) are environmental contaminants, which accumulate in the food chain and are transferred to the offspring during prenatal development through the placenta and postnatally via breast milk. It is reported that PCBs exert effects on thyroid hormone levels and brain neurotransmitter levels. Both actions may alter neuronal development. The aim of the present study was to investigate, if PCB-induced effects on concentrations of catecholamines and serotonin can be attributed to PCB-induced reductions in thyroid hormone concentrations. In addition, binding to dopamine D(1) and D(2) receptors was examined. Time-mated Wistar rats were treated prenatally with 1 mg 3,4,3',4'-tetrachlorobiphenyl (PCB 77)/kg bodyweight or the vehicle. A third group serving as the positive control received perinatally 5 mg propylthiouracil (PTU)/l drinking water. There were no overt toxic signs in dams or offspring. Thyroid hormone measurements demonstrated effects in dams and offspring up to postnatal day 40. In particular, total T(4) in serum and in the thyroid were decreased in PCB- and PTU-treated dams and offspring. Only PTU exposed rats exhibited significantly increased concentrations of TSH in the serum and pituitary. Measurement of neurotransmitters revealed changes in the PCB-exposed offspring at PND 40, while PTU-treatment was without effect. Dopamine and DOPAC were increased in the medial prefrontal cortex. In adulthood, there were no PCB-related effects on thyroid hormones and neurotransmitters. Binding studies of dopamine D1 and D2 receptors demonstrated that PCB and PTU had no influence on receptor concentration and affinity. Comparison of PCB 77 exposed offspring to PTU exposed offspring demonstrated differential effects on TSH and neurotransmitter levels, the latter result indicating that not all PCB-induced effects on the nervous system can be ascribed to decreases in thyroid hormone concentrations.

Adverse effects of environmental odours: reviewing studies on annoyance responses and symptom reporting.

Air pollution control authorities dealing with odourous emissions from industrial, municipal and agricultural activities are often faced with many complaints from the public. In Germany, the Directive on Odour in ambient air provides a regulation system for the abatement of odour annoyance. Ambient air quality standards have been established based on investigations of the relationship between ambient odour load and community annoyance reaction. This paper describes a tool for the assessment of annoyance reactions, whereby degree of annoyance is correlated with ambient odour load. Systematic exposure response relations have been established for odour annoyance responses and symptom reporting for a variety of industrial sources. However, the precision of annoyance prediction from odour exposure measures rarely exceeds r2 = 0.17 in such studies. This is partly due to the fact that person-related factors, such as age, perceived health or stress coping styles, modify exposure response relations. The contribution of intensity and unpleasantness (hedonic tone) of ambient odours as modifying the annoyance reaction is currently investigated.

Reduced levels of 1,25-dihydroxyvitamin D(3) in rat dams and offspring after exposure to a reconstituted PCB mixture.

Previous studies revealed effects of polychlorinated biphenyls (PCBs) and other polyhalogenated hydrocarbons on steroid hormone levels and hormone-dependent functions including behavior. In the present study serum concentrations of the vitamin D(3) metabolites 25-hydroxycholecalciferol (25-D) and 1,25-dihydroxycholecalciferol (1,25-D) were determined in rat dams and offspring after exposure to a PCB mixture that was reconstituted according to the congener pattern found in human breast milk. Unmated females were exposed to diets adulterated with 0; 5; 20; or 40 mg PCBs/kg diet. Exposure started 50 days prior to mating and was terminated at birth. Gestational exposure reduced serum concentrations of 1,25-D in dams in a dose-dependent manner. Concentration of 25-D was also decreased at the time of delivery, but not at weaning. Determination of 1,25-D in offspring at weaning revealed reductions in both high-exposure groups. Levels of 25-D were diminished only at the highest exposure level. Internal PCB concentrations in adipose tissue and brains exhibited a linear relation to dosages in diet. Concentrations of PCBs in brains were similar in dams and offspring at birth, but decreased at the end of lactation in dams. In offspring, values increased during this period because of continued exposure via the milk. In the adipose tissue, PCB levels were much lower in offspring than in dams. To our knowledge, this is the first report of PCB-induced effects on vitamin D(3) metabolites. In dams, reductions were seen even at the lowest exposure level used. Further studies are needed to evaluate the biological significance of these reductions in pregnant dams and possible consequences for the developing offspring.

Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on organ weights, aromatase activity, sex hormone levels, and sweet preference behavior.

Polychlorinated biphenyls (PCBs) are lipophilic industrial chemicals which are regularly detected in human breast milk, serum, and tissues. They possess hormone-modulating properties, and, when transferred transplacentally to the developing fetus, PCBs have been shown to induce persistent sex-specific neurobehavioral deficits. Interactions of PCBs with sex steroid-modulated neural differentiation could in part account for such effects. To test this hypothesis, female Long-Evans rats were exposed via food containing 40 mg/kg of either a reconstituted PCB mixture (RM), composed according to the congener-pattern in human breast milk, or the technical PCB mixture Aroclor 1254 (A1254). The exposure period started 50 days prior to mating and was terminated at birth (postnatal day 0: PND 0). Aromatase (CYP 19) activity was determined in hypothalamus/preoptic area (HPOA) brain-sections from newborn male pups. This enzyme converts testosterone (T) to 17beta-estradiol (E(2)) and plays a key role in sexual brain differentiation. Moreover, serum concentrations of T and E(2), physical development, organ weights, exposure levels, and sex-specific behavior were evaluated at different life stages. On PND 0, a reduced aromatase activity was detected in the HPOA of male RM-pups compared to controls. Female RM-weanlings exhibited significantly elevated uterine wet weights on PND 21, which is a marker for estrogenic activity. In the adult stage (PND 170), male offspring with maternal exposure to either PCB mixture showed markedly reduced testes weights and serum testosterone levels, thus demonstrating persistent antiandrogenic effects. On PND 180, male RM-rats exhibited a behavioral feminization in a sweet preference test, suggesting long-lasting changes in neuronal brain organization caused by the perinatally suppressed aromatase activity. The results suggest that maternal exposure to the RM, the pattern of which is similar to the PCB spectrum in human milk, results in more distinct effects on sex steroid-dependent processes and behavior than the technical PCB mixture A1254. PCB levels in brain and adipose tissue of the exposed offspring lay within 1-2 orders of magnitude above background concentrations in humans.

Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included.

Behavioral effects following single and combined maternal exposure to PCB 77 (3,4,3',4'-tetrachlorobiphenyl) and PCB 47 (2,4,2',4'-tetrachlorobiphenyl) in rats.

The present study has compared the neurobehavioral effects of two structurally different PCB congeners or their combination in rats. Time-mated Long-Evans rats received daily injections of the coplanar PCB 77 (3,4 3',4'-TCB: 0.5 or 1.5 mg/kg), the di-ortho-chlorinated PCB 47 (2,4,2',4'-TCB: 1.5 mg/kg) or a congener mixture (0.5 mg/kg PCB 77 + 1.0 mg/kg PCB 47) from day 7 to 18 of gestation. The PCB exposure levels in brain and perirenal fat of dams and offspring were determined by GC/ECD on gestational day 19 (GD 19), postnatal day 21 (PND 21), and PND 45. PCB 77 was accumulated to a smaller degree than PCB 47. On GD 19, PCB 77 was found to a greater extent in the brains of the offspring than in the brains of the dams, whereas the level of PCB 47 was almost the same in dams and offspring. The testing of open-field behavior in male rats on PND 18 and PND 70 revealed an altered distribution of activity with enhanced activity in the inner zone in PCB 77-treated rats compared to all other groups, while the overall activity was not changed. Distance traveled and rearing behavior on PND 340 were elevated relative to controls in all PCB-treated groups, indicating age-related effects of maternal exposure. A step-down passive avoidance task revealed decreased latencies in the PCB 77 and combined exposure groups on PND 80. Only PCB 77-treated animals showed increased latencies on PND 100 on the haloperidol-induced catalepsy test. These results indicate long-term effects of maternal exposure to PCB 77 on emotional and motor functions. At the dose levels used in the present experiments, the two congeners given in combination did not cause additive or synergistic effects. Instead, concurrent exposure to PCB 47 seemed to counteract PCB 77-induced changes in the pattern of activity.

Sex-dependent effects of maternal PCB exposure on the electroretinogram in adult rats.

The purpose of the present experiment was to evaluate the effects of developmental exposure to polychlorinated biphenyls (PCBs) on the visual system. Pregnant Long-Evans rats were treated with the ortho-chlorinated 2,2',4,4'-tetrachlorobiphenyl and/or with the coplanar 3,3',4,4'-tetrachlorobiphenyl. Total dose of PCBs was 18 mg/kg in all groups. Measurements of the flash-evoked electroretinogram (ERG) started in the offspring at an age of about 200 days. The scotopic b-wave, the maximum potential, and oscillatory potentials were recorded after dark adaptation. Amplitudes of these potentials were reduced in female rats exposed to the coplanar PCB. No differences from controls were found in females of other groups or male rats. The results indicate long-lasting effects on the scotopic ERG after maternal PCB exposure that are sex dependent and congener specific. To our knowledge, this is the first experimental report of PCB-related influences on visual processes.

Cognitive and sensorimotor functions in 6-year-old children in relation to lead and mercury levels: adjustment for intelligence and contrast sensitivity in computerized testing.

Within a larger environmental health screening program neurobehavioral measures were taken in 384 6-year-old children (mean age 74 months) in the cities of Leipzig, Gardelegen, and Duisburg. Lead concentrations in venous blood samples (PbB) and urinary mercury excretion in 24-h samples (HgU) were measured as markers of environmental exposure by electrothermal AAS. Dependent variables included two subtests from the WISC [vocabulary (V) and block design (BD)] as well as five tests from the NES2 [pattern comparison, pattern memory, tapping, simple reaction time, and the continuous performance test (CPT; child version)]. In addition, visual functions [visual acuity (TITMUS-test) and contrast sensitivity (FACT)] were tested as covariates. The overall average PbB (geometric mean) was 42.5 microg/l (upper 95% value = 89 microg/l). The overall average mercury excretion (HgU) was 0.16 microg/24 h. Whereas no significant or borderline associations between HgU and any of the target variables was found, significant negative associations were observed between PbB and verbal intelligence (WISC vocabulary but not WISC Block Design) and false-positive responses (false alarms), as well as false-negative responses (miss) in the CPT. Whereas parental education was the most important confounder for WISC performance, visual contrast sensitivity and computer familiarity also proved predictive for performance in several computer-based NES subtests. It is concluded that non-IQ measures, namely measures of sustained attention, are negatively affected in children with 95% of blood-lead levels below 90 microg/l, even after adjustment for intelligence and contrast sensitivity, whereas the causative role of lead in altering IQ functions remains somewhat equivocal, because important covariates could not be controlled for.

Myopathy: a possible effect of chronic low level lead exposure.

Morphological changes in the central nervous system and other organs have been reported in numerous studies investigating low level lead exposure. To date, however, there are no investigations on the effect of low level lead exposure on striated muscles, although varying neuromuscular changes in different species have been known for years. Rhesus monkeys were exposed pre- and postnatally to lead acetate in the diet (350 ppm or 600 ppm) over 9 years, followed by a lead free period of 32 months, while a control-group received regular diet. No signs of muscular dysfunction were evident. To elucidate neuromuscular pathomorphology frozen sections of the vastus medialis muscle were processed for routine and enzymohistological staining (Hematoxilin and Eosin, Sudan Black, Gomori, NADH, ATPase). Resin histology was processed for electron microscopy. Morphometric analysis was made with commercial software. Light microscopy revealed dose-related signs of myopathy in the lead-exposed groups. The scatter of fibre diameters was increased, and split fibers and internal nuclei were more frequent. Fibres became separated from each other by copious endomysial connective tissue. Ultrastructural examination showed hydropic mitochondria and a massively dilated sarcotubular system in the 600 ppm group. Dose-related extracellular collagen deposition increased. A heavy fibrosis was seen in the 600 ppm group. These findings are interpreted as myopathical reaction due to chronic low level lead exposure, as there were no signs of neurogenical lesion. It remains unknown how the fibrosis developed. A primary fibrosis could be based upon a developmental delay of satellite cells (expressing metalloproteases for collagen-catabolism). Lead is known to inhibit regular development in many ways if exposure has started prenatally. As the skeletal muscle is a common target of toxicity, the myotoxic effects of chronic low level lead exposure comes into question.

Visual functions in 6-year-old children in relation to lead and mercury levels.

Within a larger comparative environmental health screening program in East and West Germany we investigated functions of the developing visual system in field experiments in a total of 384 children living in three different areas. Visual functions were assessed neurophysiologically by visual-evoked potentials (VEPs) and psychophysically by measuring the contrast sensitivity (CS). Blood lead concentrations and urinary mercury levels were used as markers of environmental and/or amalgam-derived exposure, respectively. The relationships among lead and mercury concentrations and the neurophysiological and psychophysical outcomes were investigated by means of linear regression analysis. After adjusting for confounding effects, statistically significant lead-related changes were found only for some of the VEP interpeak latencies, while some of the CS values were significantly reduced with increasing mercury concentrations. All other outcome variables were not significantly related to lead or mercury levels. It is concluded that even at blood lead levels in the range of 14 to 174 micrograms/l and at very low urinary mercury levels subtle changes in visual system functions can be measured.

Developmental neurotoxicity of polychlorinated biphenyls (PCBS): cognitive and psychomotor functions in 7-month old children.

Neurobehavioral effects of polychlorinated biphenyls (PCBs) at environmental levels of exposure have been reported in cross-sectional and prospective studies in infants and children. However, observations differ for effect spectrum, persistence and effective matrix (cord plasma, maternal plasma or milk). In order to improve risk assessment by clarifying some of these uncertainties, a European multicentric study was set up. Results from the German (Düsseldorf) cohort covering 171 healthy mother-infant pairs are given. The sum of PCB congeners 138, 153 and 180 (sigma PCB) in cord plasma and maternal milk was used to describe neonatal PCB exposure. Mean sigma PCB-concentrations were 0.55 ng/ml in cord plasma and 427 ng/g fat in breastmilk. This report covers the Bayley II mental (MDI) and psychomotor development index (PDI) as well as the Fagan Test of Infant Intelligence (Visual Recognition Memory) taken at 7 months of age in relation to neonatal sigma PCB. After confounder-adjustment significant negative associations were found between sigma PCB in milk and MDI (P < 0.05), whereas the other associations proved insignificant.

Effects of maternal exposure to 3,3',4,4'-tetrachlorobiphenyl or propylthiouracil in rats trained to discriminate apomorphine from saline.

In the present experiment drug discrimination was examined in rats after maternal exposure to 3,3',4,4'-tetrachlorobiphenyl (PCB 77) using apomorphine (APO) as the training drug at a dose reported to act on dopamine D2 receptors. A group with maternal exposure to 6n-propyl-2-thiouracil (PTU) was included as a positive control for effects induced by PCB 77 on thyroid hormones. On gestational day (GD) 19 reduced levels of free and total thyroxine (FT4, TT4) and free triiodothyronine (FT3) were detected in dams exposed to PCB 77 or PTU. In the offspring decreases in levels of FT4 and TT4 were found in both treated groups on postnatal day (PND) 21, while reductions of FT3 were observed only in the PTU group. PTU-treated rats needed more daily sessions for successful discrimination between apomorphine and saline. There were no differences between groups in generalization tests and sessions with the D2/D3 agonist quinpirole, the D2 antagonist haloperidol plus APO, or with the GABAergic drug pentobarbital and only minor differences in sessions with the D1 agonist SKF-38393. Differences between controls and groups exposed to PCB 77 or PTU were detected in a blocking test using the mixed serotonin 5-HT1A agonist and partial D2 antagonist buspirone. This outcome suggests long-lasting effects by developmental exposure to PCB 77 on the interaction between dopaminergic and serotonergic processes which may be mediated by effects on thyroid hormone levels.

Neurobehavioral aspects of lead neurotoxicity in children.

Neurobehavioural toxicity in occupational lead-exposure has typically not been observed at blood lead-concentrations (PbB) below 400 micrograms/l (e.g. 1, 2), whereas in environmentally exposed children such deficit has been reported to occur down to PbB of 100-150 micrograms/l and, perhaps, even below this range (4). Both cross-sectional and prospective studies have arrived at similar conclusions in this respect. The preferred endpoint in most such studies has been the IQ-measure, which has good psychometric qualities, is sufficiently well standardized to be comparable across studies, and exhibits attractive simplicity for the regulator in a public health context. Metaanalyses on both cross sectional and prospective studies in lead exposed children have concluded that a typical doubling of PbB from 100 to 200 micrograms/l is associated with an average loss of IQ of 1-3 points (3, 4). It should also be pointed out, however, that the IQ-focus has also interfered with systematic efforts to identify more specific lead-induced functional deficits by means of more detailed neurobehavioral analyses (5). Some neuropsychological findings in lead exposed children suggest that part of the impairment resembles performance deficit found to be characteristic for children presenting with signs and symptoms of attention deficit disorder.