Polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans and birth weight and immune and thyroid function in children.

None of the publications reviewed provide clinical evidence that PCBs (polychlorinated biphenyls) and related chemicals adversely affect weight, immune, or thyroid function in infants or children born to healthy mothers. Birth weights of term infants fell within the normal range in all studies. The greatest difference between comparison groups was reported by G. G. Fein et al. (1984a, Intrauterine Exposure of Humans to PCBs: Newborn Effects, EPA-600/3-84-060, Environmental Protection Agency; 1984b, J. Pediatr. 105, 315-320). P. R. Taylor et al. (1989, Am. J. Epidemiol. 129, 395-406) reported smaller differences in occupationally exposed women and E. Dar et al. (1992, Environ. Res. 59, 189-201) found that women with higher PCB serum levels had larger babies. S. Patandin et al. (1998, Pediatr Res. 44, 538-545) found a negative association of PCB concentrations in maternal or cord plasma and birth weight of breast and formula-fed infants combined but not when breast-fed infants were analyzed separately. L. Rylander et al. (1995, Scand. J. Work Environ. Health 21, 368-375) reported decreased birth weights with higher dietary intake of contaminated fish. Thus, correlations between PCB exposure or polluted fish ingestion and birth weight were inconsistent. Thyroid and immune function were also within the normal range. In none of the papers were normal laboratory reference values provided and overall the statistically significant differences accounted for little of the variance.

Analysis of research studying the effects of polychlorinated biphenyls and related chemicals on neurobehavioral development in children.

During the past 25 y numerous studies have been performed in infants and children to determine whether environmental exposure to polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, dibenzofurans (PCDFs) and dichlorodiphenyl trichloroethane is causally associated with neurobehavioral effects. In addition, 1 episode of poisoning with PCDFs occurred in Taiwan in 1978. This poisoning outbreak is referred to as Yu-Cheng, oil disease, since the PCDFs and PCBs had accidentally contaminated cooking oil. In the aggregate the studies reviewed here show no conclusive evidence that environmental exposure to these chemicals affect the neurobehavioral development of infants and children.

Mortality in male and female capacitor workers exposed to polychlorinated biphenyls.

A mortality study was conducted in workers with at least 90 days' exposure to polychlorinated biphenyls (PCBs) between 1946 and 1977. Vital status was established for 98.7% of the 7075 workers studied. In hourly male workers, the mortality from all cancers was significantly below expected (standardized mortality ratio [SMR] = 81; 95% confidence interval [CI], = 68 to 97) and comparable to expected (SMR = 110; 95% CI, 93 to 129) in hourly female workers. No significant elevations in mortality for any site-specific cause were found in the hourly cohort. All-cancer mortality was significantly below expected in salaried males (SMR = 69; 95% CI, 52 to 90) and comparable to expected in salaried females (SMR = 75; 95% CI, 45 to 118). No significant elevations were seen in the most highly exposed workers, nor did SMRs increase with length of cumulative employment and latency. None of the previously reported specific excesses in cancer mortality were seen. This is the largest cohort of male and female workers exposed to PCBs. The lack of any significant elevations in the site-specific cancer mortality of the production workers adds important information about human health effects of PCBs.

Selected other effects and TEFs.

The half-lives and tissue distribution of chlorinated dibenzodioxins and dibenzofurans in humans are reviewed. An attempt is made to correlate adverse effects observed in humans such as chloracne, Yusho, Yucheng, and Seveso with tissue levels. No causal inferences should be made in the Ranch Hand studies because TCDD serum levels are slightly higher in older persons and in persons who have diseases related to their lipid metabolism and their age. These differences cannot be used in the context of a dose-response relationship but should be used in the context of variations in the distribution of PCDD and PCDF levels within different subpopulations. Based on these observations in humans, TEF values for mixtures of PCDD and PCDF are poor predictors of human risk.

Polychlorinated biphenyls (PCBs) and human health: an update.

Polychlorinated biphenyls (PCBs) are a mixture of 209 different chlorinated biphenyl congeners (forms) of which 36 are environmentally relevant. PCBs are lipid (fat)-soluble, stable compounds. PCBs may be contaminated with more highly toxic polychlorinated dibenzofurans (PCDFs). Some PCDFs were primarily responsible for the two poisoning outbreaks--Yusho and Yu-Cheng. Based on the reports on workers and the general population, no clear and convincing evidence that PCB exposures were casually associated with adverse health effects was advanced; this included cancer for a wide range of body burdens and exposures for serum PCB concentrations > 1000 ppb (micrograms/l) and adipose PCB levels > 400 ppm (mg/kg). No meaningful reproductive problems have been identified in female capacitor workers. In the opinion of the review author, the available evidence for cancer and for reproductive effects is inconclusive. Adverse neurobehavioral effects in infants and young children have been reported in a study of women in the general population and a study of fish eaters and their offspring. The adverse effects observed in the two studies were not the same; the exposure assessments in both studies are not well defined and have many uncertainties. Subhuman primates appear to be more sensitive to reproductive and other adverse effects of PCBs than humans. Obvious external clinical signs are observed in the offspring of subhuman primates at dosage levels below those experienced by female capacitor workers and members of the general population prior to the control of PCBs.

Determining acceptable risks: experimental and epidemiological issues.

The extent to which results of experimental toxicology studies can be used to assess risk for humans varies. Administering high doses of chemicals to experimental animals may produce indirect adverse metabolic and nutritional effects, and metabolic pathways may differ at high and low doses. The rate of metabolism at high and low doses and the metabolic pathways of chemicals in different species are important for establishing the reasons for differences in species responses. Animal species best suited to serve as a surrogate for humans vary for different chemicals. For realistic risk assessments, more detailed information on the toxicokinetics of chemicals in humans is needed. As data are developed to link early biochemical changes with future disease, it is important to determine their predictive value. Our present expectations of using various biomarkers to predict future health outcomes may be unrealistic. More baseline data are needed to determine which biomarkers are expressions of exposure and which are predictors of future disease. It is also unclear how lifestyle affects most biomarkers.

Management of children with slightly elevated blood lead levels.

OBJECTIVE: To determine whether counseling of parents reduced blood lead levels in their young children. PARTICIPANTS AND METHODS: A lead exposure study was conducted in the vicinity of a defunct lead smelter. A total of 827 volunteers including 490 children younger than 6 years participated in the study. The mean venous blood lead level in the 490 children was 0.33 mumol/L (6.9 micrograms/dL), with a range of 0.03 to 1.94 mumol/L (0.7 to 40.2 micrograms/dL). A total of 78 (16%) children had blood lead levels > or = 0.48 mumol/L (10 micrograms/dL). However, only 5 (1%) of the children had blood lead levels of > or = 1.21 mumol/L (25 micrograms/dL). The blood lead levels in this community were much lower than levels reported in earlier studies in many areas of the United States, when lead levels in air and in food were higher. Most houses in the study community were built before 1920 and had high lead paint levels. High levels of lead were also found in many house dust and soil samples. Intervention consisted of home visits and counseling of parents of children with blood lead levels of > or = 0.48 mumol/L (10 micrograms/dL). RESULTS: In children with initial blood lead levels of > or = 0.48 mumol/L (10 micrograms/dL) the blood lead test was repeated 4 months later. The arithmetic mean blood lead level 4 months later showed a decrease from 0.72 mumol/L (15 micrograms/dL) to 0.38 mumol/L (7.8 micrograms/dL). An additional blood sample was taken 1 year after the first sample in a subset of 30 children. These children showed a mean blood lead level of 0.43 mumol/L (9 micrograms/dL) at the 1-year follow-up, whereas their mean blood lead level at the 4-month follow-up had been 0.38 mumol/L (8 micrograms/dL). CONCLUSION: Educating parents proved a very effective tool. Further studies are needed in larger populations to evaluate the effectiveness of this approach.

Acute toxicity of gasoline and some additives.

The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels.

Consumption of fish: benefits and perceived risk.

Fish, a useful source of protein, may be polluted by microbes, natural toxins, and/or synthetic chemicals. However, based on a review of the U.S. General Accounting Office, "There does not appear to be a compelling case to implement a mandatory comprehensive federal seafood inspection program." Although earlier studies showed higher body burdens of polychlorinated biphenyls (PCBs) in populations who consumed a lot of fish from polluted waterways, a recent study refutes these observations. No information is available in the United States on the levels of polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) in anglers who consume a great deal of fish presumed to be contaminated by these chemicals.

Non-specificity of clinical signs and symptoms caused by environmental chemicals.

1. A review of the scientific literature revealed that 220 environmental chemicals had caused documented systemic toxicity in humans. This number is relatively small compared to the large number of industrial chemicals in the environment. 2. A total of 149 of these chemicals were verified as neurotoxins, thus emphasizing the sensitivity of this target organ. Despite the exclusion of chemicals that cause airway irritation only, 99 chemicals caused adverse effects on the respiratory system. Toxicity to the liver, kidneys and blood forming organs was less frequent. 3. Most of the individual clinical effects had a very low specificity in cases of human intoxication. Of 80 major signs and symptoms, 17 had only a single documented chemical aetiology. However, the combination of two or more signs or symptoms was found to provide an improved guidance to aetiological diagnosis. The paucity of specific signs and symptoms is probably one of the reasons that only 220 environmental chemicals have been documented as causes of human disease.

Kashin-Beck disease: a cross-sectional study in seven villages in the People's Republic of China.

Kashin-Beck disease (KBD) is an endemic disease that occurs in certain parts of the People's Republic of China and in Russia. The etiology of the disease is unknown. Selenium deficiency, mycotoxins, and chelating agents such as humic acid and decaying plant material from walnut tree forests have been suggested as causal agents. The primary lesion of this disease is the selective coagulative necrosis of the hypertrophic chondrocytes at the base of the articular and growth plate cartilages. A cross-sectional study was performed in the People's Republic of China in 7 villages, to focus on information about life styles, food consumption, and environmental factors from the village population where the disease is endemic. A total of 425 children were examined, of which 71 children had KBD. Results of detailed food consumption data analyses showed that certain combinations of food substances high in protein had a protective effect. It was also found that the disease was twice as prevalent in onset in boys as in girls, in the 12-yr-old age group. The overall onset of illness in this group of children ranged from 4 to 13 yr. Either the joints of the fingers or one ankle was affected first. Many of these children also had discolored teeth. However, this finding was unrelated to KBD.

How toxic is 2,3,7,8-tetrachlorodibenzodioxin to humans?

The tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) measured in different species are reviewed. Based on the correlation of tissue levels and a toxic response in different species, humans are less or no more susceptible to the toxic effects of TCDD than most of the laboratory animals that have been studied. Thus, the present exposure of the general population to environmental levels of TCDD are related compounds should not be of concern.

Fibers in idiopathic retroperitoneal fibrosis: a case report.

A case of idiopathic retroperitoneal fibrosis in a 33-yr-old female is reported. Many fiber-like crystals were noted within macrophages and the interstitial tissue of the lesion. The crystals appeared tan in hematoxylin- and eosin-stained slides and were birefringent under polarized light. The identity of the crystals was not established.

Porphyrins and hepatotoxicity.

Human porphyrias are rare inborn disorders of porphyrin metabolism. Porphyria cutanea tarda is one such disorder, which may occur spontaneously after the ingestion of drugs and alcohol. This is the "constitutional" type and is associated with a deficiency of uroporphyrinogen decarboxylase in the liver. This constitutional type must be differentiated from the "acquired" type, which occurred in hundreds of people poisoned by hexachlorobenzene in Turkey. Morphological changes observed in the livers of animals and humans vary greatly. Porphyria cutanea tarda may be associated with very little liver pathology or with very pronounced changes, depending on the agent causing the porphyria. Usually, the liver has an increased iron load, and mitochondria contain a crystalline material.

Compensation of victims exposed to environmental pollutants.

The sponsors of the Comprehensive Environmental Response Compensation and Liability Act of 1980 (CERCLA), also known as "Superfund," agreed that more information was needed regarding legal remedies for injuries to persons from exposures to hazardous wastes. There has been a rush in Congress and some states to introduce "victims' compensation" bills to facilitate recovery for personal injury from exposure to hazardous waste sites. Such approaches are overly simplistic and totally disregard the reach and shortfall of scientific data.

Characterization of pancreatic-type tissue in the liver of rat induced by polychlorinated biphenyls.

Pancreatic-type tissue induced in the livers of rats treated with polychlorinated biphenyls was characterized by transmission electron microscopy and high-resolution immunocytochemistry. The cells of pancreatic-type tissue were arranged as acini and in small groups. By electron microscopy the pancreatic-type tissue showed features very similar to normal pancreatic acinar tissue, such as well developed rough endoplasmic reticulum (RER), large numbers of mature zymogen granules, and a basally located nucleus. Protein A-gold imunocytochemical technique showed localization of amylase and trypsinogen over the zymogen granules and RER. These findings confirm that this tissue in the liver is morphologically and functionally identical to pancreatic acinar tissue.