Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan.

In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by thermally degraded polychlorinated biphenyls. Because these chemicals persist in human tissue, children born to female patients after the outbreak were exposed in utero. In 1985, 117 children born to affected women and 108 unexposed controls were examined and evaluated. The exposed children were shorter and lighter than controls; they had abnormalities of gingiva, skin, nails, teeth, and lungs more frequently than did controls. The exposed children showed delay of developmental milestones, deficits on formal developmental testing, and abnormalities on behavioral assessment. These findings are most consistent with a generalized disorder of ectodermal tissue. This syndrome is one of very few documented to result from transplacental exposure to pollutant chemicals.

Factors influencing the difference between maternal and cord blood lead.

AIMS: To determine the factors that affect why some infants receive higher exposures relative to the mother's body burden than do others. METHODS: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. RESULTS: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. CONCLUSION: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.

PCBs, DDE, and child development at 18 and 24 months.

To determine whether perinatal exposure to "background" levels of polychlorinated biphenyls (PCBs) or dichlorodiphenyldichloroethene (DDE) affected child development, we followed a cohort of children through the age of 2 years; 676 were tested at 18 months and 670 at 24 months with the Bayley Scales. Transplacental and cumulative exposures from breast milk to both chemicals were estimated for each child from analyses of breast milk and other samples. Bayley testing was done without knowing the chemical levels. At 18 and 24 months, adjusted scores on the psychomotor scales were 4 to 9 points lower among children in the top fifth percentile of transplacental PCB exposure, significantly so at 24 months. There were no consistent effects apparent from exposure to PCBs through breast milk, nor from DDE exposure. We conclude that there is a small delay in motor maturation attributable to transplacental exposure to PCBs that is still detectable at 24 months. There is no evidence of an effect from the larger but later exposure through breast milk, although effects may emerge as the children age.

Monitoring breast milk contamination to detect hazards from waste disposal.

Human milk is a repository for certain classes of long-lived, fat-soluble environmental contaminant chemicals. Some members of this class, such as the chlorinated pesticides and the chlorinated biphenyls, can be expected to be present at chemical waste disposal sites. Analysis of samples of breast milk obtained from women near such a site could provide documentation that exposure has taken place. However, background contamination is present and must be dealt with by the collection of comparison samples. Sample collection can be difficult because of the low level of chemicals being sought, and thus the possibility of sample contamination. The diagnostic and public health consequences of contaminated breast milk are not clear at this time, and thus chemical analysis of milk should be carried out in a research setting. Despite these difficulties, breast milk monitoring has been a successful tool in certain investigations of the spread of environmental chemicals.

Environmental poisoning of children--lessons from the past.

Children have physiologic and behavioral characteristics that make them vulnerable to damage from environmental chemicals. In the past, there have been episodes in which children became ill or died from environmental exposures that spared adults or affected them less severely. Among the characteristics leading to children's sensitivity are their limited diets, dividing cells, differentiating organs and organ systems, slow or absent detoxification mechanisms, long life expectancy with the resulting ability to express damage with delayed consequences, and the severe metabolic demands of growth. There have been large outbreaks of poisonings involving children in Asia and Turkey, and some of the less obvious effects of chemicals have appeared in children in the United States. Although the United States has been spared a widespread outbreak of severe poisoning, such an incident is possible and would likely have greater consequences for children than adults.

Study of human lactation for effects of environmental contaminants: the North Carolina Breast Milk and Formula Project and some other ideas.

The presence of environmental contaminant chemicals in human milk, their demonstrated toxicity, and the lack of data in human beings led to the North Carolina Breast Milk and Formula project, a three-center prospective birth cohort study of 856 children. In this study, we measure polychlorinated biphenyls (PCBs) and DDE in milk and other fluids, follow the course of lactation, and note growth, morbidity and development in the children. Lactation is hormonally complicated and has parts that are plausibly interfered with by contaminant chemicals, and certain kinds of morbidity that occur in breastfed children might also represent the result of chemical contamination of milk. Preliminary data analysis confirms the widespread presence of chemicals in milk; women with higher DDE levels do not breast-feed as long, but this is not true for women with higher PCBs. Besides this study, several case-control or survey-type studies, such as studies of failure to thrive, certain rashes, or short-term breast-feeding would be helpful. Laboratory studies of enzyme induction are now feasible in children and might be a very sensitive if not totally specific endpoint for study of PCBs in milk.

Chemical contaminants, pharmacokinetics, and the lactating mother.

We review the commonly occurring persistent pesticides and industrial chemicals in breast milk. These chemicals are dichlorodiphenyl trichloroethane as dichlorodiphenyl dichloroethene dieldrin, chlordane as oxychlordane, heptachlor, polychlorinated biphenyls, polychlorinated dibenzofurans, and polychlorinated dibenzodioxins. We present a worked example of the kinds of pharmacokinetic assumptions and calculations necessary for setting regulatory limits of contaminants in the food supply, calculating dose of chemical contaminants to the nursed infant, converting risks from lifetime exposure in laboratory animals to risks for short-term exposure in humans, and estimating the excess cancer risk to the nursed infant.

Potential reproductive and postnatal morbidity from exposure to polychlorinated biphenyls: epidemiologic considerations.

There is both laboratory and epidemiologic evidence that PCBs are toxic to several phases of reproduction. Workplace exposure is an important but small part of the exposure to these compounds, since most of the population has detectable levels in blood or fat. Studies in the general population on PCBs and reproduction have not been done. Some studies in workers are under way, and in epidemic PCB poisonings, small babies with a distinct clinical syndrome are seen. We review some of the laboratory and epidemiologic data and the methods available for study of reproduction in humans; study of any highly exposed group should be done and studies of spontaneous abortion, birth weight and certain congenital anomalies should look for an effect of PCBs.

Chloracne, goiter, arthritis, and anemia after polychlorinated biphenyl poisoning: 14-year follow-Up of the Taiwan Yucheng cohort.

In 1979, a mass poisoning involving 2,000 people occurred in central Taiwan from ingestion of cooking oil contaminated by polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs). We studied the prevalence of medical conditions in the exposed individuals and in a neighborhood control group. Starting with a registry of the exposed individuals from 1983, we updated the addresses of exposed individuals and identified a control group matched for age, sex, and neighborhood in 1979. In 1993, individuals 30 years of age or older were interviewed by telephone. We obtained usable information from 795 exposed subjects and 693 control subjects. Lifetime prevalence of chloracne, abnormal nails, hyperkeratosis, skin allergy, goiter, headache, gum pigmentation, and broken teeth were observed more frequently in the PCB/PCDF-exposed men and women. The exposed women reported anemia 2. 3 times more frequently than controls. The exposed men reported arthritis and herniated intervertebral disks 4.1 and 2.9 times, respectively, more frequently than controls. There was no difference in reported prevalences of other medical conditions. We conclude that Taiwanese people exposed to high levels of PCBs and PCDFs reported more frequent medical problems, including skin diseases, goiter, anemia, and joint and spine diseases.

Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng cohort.

BACKGROUND: In 1979 in Taiwan, about 2000 people were poisoned by cooking oil contaminated with heat-degraded polychlorinated biphenyls (PCBs). Victims developed chloracne and other symptoms; the illness is called Yucheng (oil disease). The chemicals persist in the victims' bodies and some are toxic to the female reproductive system in experimental animals. METHODS: In 1993-1994, we identified the living Yucheng women and neighbourhood controls and interviewed them about their reproductive experience. Of the 596 living Yucheng women aged 30-59 years, we found 368, and interviewed 356. We identified 329 controls, and interviewed 312. RESULTS: Of the Yucheng women, 16% reported abnormal menstrual bleeding compared to 8% (P < 0.05) of control women; 4.2% versus 1.7% reported a stillbirth since 1979 (P = 0.068). Other characteristics of the menses, fertility, frequency of intercourse, and age at menopause appeared unaffected. More of the Yucheng women reported that one of their offspring had died during childhood (10.2% versus 6.1%, P < 0. 05), and that they had decided to limit childbearing because of health problems (7% versus 2%, P = 0.01). CONCLUSIONS: These findings suggest that high level PCB/polychlorinated dibenzofuran (PCDF) exposure has some effect on female endocrine and reproductive function.

Pollutants in breast milk.

OBJECTIVE: To review data on the occurrence and toxicity of the commonly reported pesticides and industrial environmental pollutant chemicals in breast milk. DATA SOURCES: Continuous automated literature surveillance plus contact with investigators and governmental agencies. STUDY SELECTIONS: For data on occurrence, the most recent data from the largest data sets on the most representative donors were used. For data on toxicity, the primary report that was publicly available was used. DATA EXTRACTION: When necessary, data were reexpressed or concentrations were rescaled. The original investigator was contacted if necessary. DATA SYNTHESIS: Although pollutant chemicals are readily detected in most human milk worldwide, there is little evidence for consequent morbidity in nurslings. There have been several mass poisonings in which chemicals that were transmitted through breast milk clearly affected children who were breast-fed, and there is some evidence that prenatal exposure to background levels resulted in mild developmental delay and that lactation per se was disturbed. CONCLUSIONS: Breast-feeding is recommended despite the presence of chemical residues. The prenatal period in the child and the initiation of lactation in the mother may be sensitive periods to the toxicity of the chemicals that are considered here, and the potential for poisoning at higher levels is clear. However, in the vast majority of women, the benefits of breast-feeding appear to outweigh the risks, and those who advise women about infant nutrition should continue to support breast-feeding.

Behavioral and emotional problems in Chinese adolescents: parent and teacher reports.

OBJECTIVE: This study examined behavioral and emotional problems in Chinese adolescents. METHOD: A sample of 1,694 adolescents aged 12 to 16 years participated in this study in 1997. Parents completed the Child Behavior Checklist (CBCL), and teachers completed the Teacher's Report Form (TRF). RESULTS: For both parent and teacher reports, internalizing syndromes were scored higher in girls and externalizing syndromes were scored higher in boys. Scores on most of the CBCL and TRF subscales were higher for the older adolescents. The overall prevalence rates of parent- and teacher-reported behavioral problems were 23.1% and 19.2%, respectively. The eight cross-informant syndromes were highly comorbid, with a significant association across syndromes (mean odds ratio = 16.1 for CBCL and 22.5 for TRF). Correlations between parent and teacher reports were 0.51 for eight subscales and 0.68 for Total Problems. CONCLUSIONS: These findings demonstrate that behavioral and emotional problems tend to increase with age and cluster in the same individuals. The prevalence rates of behavioral problems in Chinese adolescents are comparable to those reported in Western countries. In contrast to findings for Western samples, parent reports of behavioral problems were highly correlated with teacher reports.

Neurotoxicology of PCBs and related compounds.

Polychlorinated biphenyls (PCBs) are a family of 209 chemicals with two linked phenyl rings and variable chlorination. They are clear oils at room temperature. They were produced from the 1930s until banned in the 1970s because of toxicity and evidence of widespread environmental contamination. They were used mostly as insulators in electrical equipment; their widespread occurrence in the environment is more a consequence of uncontrolled disposal than of deliberate dissemination. In Asia, there have been two outbreaks of poisoning due to cooking oil contaminated by thermally degraded PCBs. Studies in workers exposed chronically to "clean" PCBs, workers exposed acutely to thermally degraded PCBs in clean-up of fires, and adult patients in Asia who ingested contaminated rice oil consistently show slowed nerve conduction and sometimes show headache, lassitude, and other CNS symptoms. In children exposed to background levels in the US, those with the highest transplacental exposure show hypotonia and hyporeflexia at birth and slowed motor development through age two, a defect in visual memory processing at 7 mon, and defects in short term memory at 4 years. Despite the presence of PCBs in breast milk, no association between breast milk exposure and any measured outcome has been seen other than lower activity levels at 4 years among long term breast fed children at the highest PCB levels. In Asia, children who were in utero at or after the 1968 exposure in Japan or the 1979 exposure in Taiwan showed clinically evident developmental delay. In Taiwan, the children were shown to have a variety of ectodermal defects, but the association between these defects and developmental delay was weak.(ABSTRACT TRUNCATED AT 250 WORDS)

Polychlorinated biphenyls and the developing nervous system: cross-species comparisons.

Polychlorinated biphenyls are stable, lipophilic industrial compounds that are present in residue levels in human tissue, wildlife, and freshwater sediment. They are toxic, and are known to cross the placenta and intoxicate the fetus. Two large outbreaks of PCB poisoning have occurred in Asia; women pregnant at or after the exposures had children who were developmentally impaired. Laboratory experiments in rhesus monkeys and rodents, designed to assess neural or developmental effects, show altered activity levels, impaired learning, and delayed ontogeny of reflexes. Children exposed transplacentally to levels considered to be background in the U.S. have hypotonia and hyporeflexia at birth, delay in psychomotor development at 6 and 12 months, and poorer visual recognition memory at 7 months. Allowing for differences in testing, effects are roughly similar across species, but current methods used to calculate allowable or reference doses give results up to 4 orders of magnitude apart, with the lowest level based on the neurotoxicology level coming from the human data.

In utero PCB/PCDF exposure: relation of developmental delay to dysmorphology and dose.

In 1979, there was an outbreak of food poisoning in central Taiwan due to cooking oil contaminated with polychlorinated biphenyls and their thermal degradation products. Starting in 1985, we studied 128 children born to exposed women after the oil was removed from the market; the exposure of these children was transplacental or through breast milk. We also studied matched controls. The exposed children exhibited developmental delays as measured by parental report, by neurologic examination, and by standard cognitive tests; delay was seen at all ages and persisted over time. Delay was greater in children who were smaller in size and in children who had exhibited neonatal symptoms of intoxication. Children with a history of nail deformity also were delayed. However, there was little relationship between other physical findings or measures of maternal exposure and developmental delay. There was some indication that the child's prenatal exposure was more important to developmental delay than was exposure through breast milk.

Neurobehavioral test strategies for environmental exposures in pediatric populations.

The Agency for Toxic Substances and Disease Registry convened a workshop in Atlanta, GA, that evaluated approaches and methods to ascertain whether there are neurobehavioral sequelae to children and adults exposed to hazardous substances in the environment. This article, developed from that workshop, addresses the feasibility of employing extant neurobehavioral tests to screen pediatric populations. A matrix lists basic functions to be assessed during eight developmental periods ranging from birth to high school. The best of these neurobehavioral tests for pediatric populations and the types of assessment tools that are still needed are discussed. We make 10 specific recommendations to establish a hazardous substances neurobehavioral screen for pediatric populations, including appointing a review panel, developing a structured questionnaire, convening a conference on design and analysis, addressing minority and socially disadvantaged populations, coordinating adult and child assessment methods, information sharing among Federal agencies, baseline data, methodology research, research associated with hazardous worksites, and establishment of a pediatric databank.

Breast-feeding and cognitive development.

Eight-hundred fifty-five newborns were enrolled in a prospective study between 1978 and 1982 and then followed through school age. To determine whether the mode of infant feeding affected developmental scores or school grades, prospective data were collected on how the children were fed; 788 of the children had Bayley tests at 6 months, 720 at 12 months, 676 at 18 months and 670 at 2 years. McCarthy testing was done on 645 children at 3 years, 628 at 4 years and 636 at 5 years. Testers were not specifically blind to feeding method. The families provided report cards from grade 3 or higher for 366 children. There were statistically significant but small increases in scores among breast-fed children on at least some subscales of the Bayley and McCarthy at all time points from 2 years through 5 years and slightly higher English grades on report cards in both crude analyses and in multivariate analyses that allowed adjustment for the most plausible confounding variables. We conclude that, in a volunteer, 95% white sample of middle class children, those breast-fed scored slightly better than those bottle fed; the effect is small but still detectable at school age.

Aflatoxin and Reye's syndrome: a study of livers from deceased cases.

In order to reinvestigate a strong reported association, we attempted to identify aflatoxin in the livers of 12 children who presumably died of Reye's Syndrome and in the liver of one child who died accidentally. Aflatoxins were detected, but not confirmed in only one of the liver specimens (limits of detection 20 ppt). In addition, the microscopic appearance of the livers was reviewed. Although most of the cases fit the clinical definition of Reye's Syndrome, the microscopic appearance of the liver was varied. We conclude that aflatoxin is not regularly recoverable from cases of Reye's Syndrome at a high rate, and question the proposed etiologic relationship. We confirm the varied appearance of the liver late in the course of Reye's Syndrome; however, microvesicular fat was present in most cases.

Urinary porphyrins in children exposed transplacentally to polyhalogenated aromatics in Taiwan.

In 1979, there was a large (greater than 2,000 cases) outbreak of poisoning due to contaminated rice oil in central Taiwan. The causal agent was a mixture of thermally degraded polychlorinated biphenyls (PCBs), polychlorinated quaterphenyls, and polychlorinated dibenzofurans, which had become mixed with the oil during processing. Patients remained symptomatic for several years afterward, and the chemicals persisted in their tissue. Women who became pregnant had children with high perinatal mortality and a dysmorphic syndrome. We examined urines from 75 children born to exposed mothers after the oil was confiscated, 74 controls, and 12 sibs of the exposed children. Four of the transplacentally exposed children, 2 controls, and 1 sib had a type B hepatic porphyria (i.e., uroporphyrin greater than coproporphyrin); total porphyrin excretion was elevated in the exposed children as a group (95 vs. 81 micrograms/L); and 8 of the 75 exposed children and 2 controls had total urinary porphyrin concentrations of greater than 200 micrograms/L.

Preventing lead poisoning in children: can the US experience inform other countries? The case of Poland.

Exposure to excess lead during childhood is preventable, but nowhere has that goal been achieved. In the US, recommendations for prevention of childhood lead poisoning are issued by the Centres for Disease Control and Prevention, based on periodically updated population-based data on the prevalence of lead poisoning by age and blood lead level. A well developed public health infrastructure is to provide case management to the lead exposed children. In Poland, the social and economic transitions of the last decade changed the potential for childhood lead exposure, and there has been a profound restructuring of the health care system. Blood lead testing in children is performed outside the primary care. Data on blood lead levels are not collected and analysed centrally. The range of follow-up services may differ among the regions, depending on the local expertise. An updated approach to prevention of childhood lead poisoning, making better use of the existing expertise and involving primary care providers, needs consideration. Complex public health programs like this of lead poisoning prevention cannot be transplanted whole to other countries. However, experiences gained by the US might provide valuable suggestions for others, even though the US policy has flaws and is not fully implemented. Discussing proposal for Poland in light of the current US practice highlights the necessity of reliable estimates of the exposed population for rational policy. It also helps to define research questions relevant to public health practice in Poland, and confirms that prevention of lead poisoning in children requires the coordinated work of different professionals.