Children's health and the environment: a new agenda for prevention research.

Patterns of illness in American children have changed dramatically in this century. The ancient infectious diseases have largely been controlled. The major diseases confronting children now are chronic and disabling conditions termed the "new pediatric morbidity"--asthma mortality has doubled; leukemia and brain cancer have increased in incidence; neurodevelopmental dysfunction is widespread; hypospadias incidence has doubled. Chemical toxicants in the environment as well as poverty, racism, and inequitable access to medical care are factors known and suspected to contribute to causation of these pediatric diseases. Children are at risk of exposure to over 15,000 high-production-volume synthetic chemicals, nearly all of them developed in the past 50 years. These chemicals are used widely in consumer products and are dispersed in the environment. More than half are untested for toxicity. Children appear uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological susceptibility. To prevent disease of environmental origin in America's children, the Children's Environmental Health Network (CEHN) calls for a comprehensive, national, child-centered agenda. This agenda must recognize children's vulnerabilities to environmental toxicants. It must encompass a) a new prevention-oriented research focus; b) a new child-centered paradigm for health risk assessment and policy formulation; and c) a campaign to educate the public, health professionals, and policy makers that environmental disease is caused by preventable exposures and is therefore avoidable. To anchor the agenda, CEHN calls for long-term, stable investment and for creation of a national network of pediatric environmental health research and prevention centers.

Neurotoxicity of mercury--indicators and effects of low-level exposure: overview.

The theme of the Twelfth International Neurotoxicology Conference was Neurotoxicity of Mercury: Indicators and Effects of Low-Level Exposure. Papers related to the topic appear in NeuroToxicology 16(4):1995 and 17(1):1996 (this issue). This overview provides the reader with a guide by discussing the papers under the topics of human exposure, human health effects, risk assessment, mechanism of action, and primate models.

Monkey versus human performance in the NCTR Operant Test Battery.

A battery of operant behavioral tasks, designed to monitor complex "cognitive" functions in monkeys, was adapted for use in children. Adaptations were then incorporated into the monkey battery so that monkeys and children performed exactly the same tasks. Food pellets served as reinforcers for monkeys; nickels for children. Correct responding in a task is thought to depend upon relatively specific brain functions including short-term memory and attention, learning, time perception, motivation, and color and position discrimination. Eight 4-year-old rhesus monkeys served as subjects, and groups (n = 10 to 20) of 4- to 8-year-old children were recruited if they were not known to have any neurological, academic or behavioral problems. In performance of only the learning task was there any significant difference between monkeys and children. This difference was in response rate (not accuracy), with the monkeys responding faster than children. This lone difference in operant responding between monkeys and children was likely due to the fact that monkeys generally use all four appendages to respond whereas children generally do not.

How ADN students can learn prenatal (healthy) care.

This article describes the problem-solving steps of how an unsupervised clinical experience can be successfully implemented at the ADN level so that large numbers of students can meet traditional clinical objectives in a nontraditional manner. Learning experiences covered are: patient teaching, interviewing, care planning - coordinated with theories of learning and program philosophy/purpose.

Quantitation of complex brain function in children: preliminary evaluation using a nonhuman primate behavioral test battery.

The performance of twenty children (3-11 years of age) in a complex operant test battery (OTB) was evaluated. The operant schedules, or tasks, used in the OTB were identical to those originally designed and currently used to assess complex brain function in nonhuman primate laboratory animals (monkeys). The OTB consisted of five operant tasks: 1) Progressive-Ratio [PR]; 2) Conditioned-Position Responding [CPR]; 3) Temporal Response Differentiation [TRD]; 4) Delayed Matching-to-Sample [DMTS] and 5) Incremental Repeated Acquisition [IRA]. These operant tasks are thought to engender responding indicative of processes associated with: 1) motivation; 2) color and position discrimination; 3) time-perception; 4) short-term memory and attention; and 5) learning, respectively. The parameters for each of the tasks in the OTB were optimized for use in the clinical setting to assess cognitive function in children. In the small population studied, performance in the IRA, DMB and TRD tasks was age related. Of the four 6-yr-olds studied, only those categorized as having either learning disabilities (LD, n = 1) or attention deficit disorders (ADD, n = 2) did not complete the "learning" task. By comparison of human and monkey performance in the OTB, we also hope to validate the use of laboratory animal models in research efforts designed to yield insight into complex human brain function. It is also hoped that assessment of children's performance in the tasks in the OTB will assist in the diagnosis and treatment of certain childhood disorders such as learning disabilities and/or attention deficit disorders.

Pulmonary oncocytoma. Report of a case with cytologic, histologic and electron microscopic study.

The cytology of a pulmonary oncocytoma diagnosed by bronchial brushings is described along with the light and electron microscopic findings. Ultrastructurally, the tumor cells showed mitochondrial hyperplasia and an absence of neurosecretory granules. The possible histogenesis of pulmonary oncocytomas is discussed.

Prenatal chlordane exposure: effects on plasma corticosterone concentrations over the lifespan of mice.

Developmental exposure to nonteratogenic doses of the organochlorine pesticide Chlordane has been reported to alter endocrine function of apparently normal offspring evaluated at 101 days of age (J.S. Cranmer, D.L. Avery, R.R. Grady, and J.S. Kitay, 1978, J. Environ. Pathol. Toxicol. 2, 357-369). The long-term study reported here was conducted in cohort groups of identically treated mice to determine if prenatal exposure to Chlordane had a persistent effect on endocrine function over the lifespan of the exposed offspring as determined by alterations in plasma concentrations of corticosterone at 400 and 800 days of age. Dihybrid female mice were exposed throughout gestation to 0.16 or 8.00 mg/kg/day Chlordane and endocrine function of offspring was evaluated at three timepoints in their lifespan. Adrenal production and liver reduction capacity for corticosterone (the primary glucocorticoid in rodents) and plasma concentration of corticosterone were measured at 101 days. In this and three previous studies, changes in plasma levels of corticosterone proved to be a reliable indicator of changes in adrenal and/or liver function, thus, only plasma concentrations of corticosterone were determined at 400 and 800 days of age. Plasma corticosterone concentrations of male mice prenatally exposed to the lower Chlordane dose were significantly (P less than 0.01) elevated when measured at 101 days of age. This abnormal elevation (P less than 0.05) was recorded in both dose groups when male mice were examined at 400 days of age. At 800 days of age, no differences from control were found for male offspring in the lower dose group; insufficient numbers of offspring in the higher dose group survived to be evaluated. An effect of Chlordane on corticosterone metabolism in female offspring was observed only in the 0.16 mg/kg dose group at 400 days of age when plasma concentrations of corticosterone were significantly (P less than 0.05) increased. Results suggest that prenatal exposure to nonteratogenic doses of Chlordane (1) had a significant effect on endocrine function (corticosterone control), (2) affected males more than females, and (3) produced changes (increased plasma corticosterone levels) which were detectable at adulthood and persisted into middle age. The mechanisms responsible for these persistent changes in corticosterone metabolism remain to be elucidated.

Developmental neuropathology of organotin compounds.

The literature concerning the developmental neuropathology of organotins is reviewed. To date, neuropathological effects have been convincingly demonstrated for trimethyltin (TMT) and triethyltin (TET). Both compounds may damage the developing CNS; however they have different cellular targets. TMT is a neuronotoxin which damages areas of the limbic system, cerebral cortex, and brainstem. TET is a myelinotoxin which causes massive myelinic edema by yet undetermined mechanisms. Neuronal death is also seen following TET intoxication during the neonatal period, possibly as a result of elevated intracranial pressure. The neuropathological features of TMT and TET intoxication during early life are presented. Neurochemical and behavioral alterations resulting from congenital and/or neonatal exposure to organotins are also discussed.

Immunocompetence over the lifespan of mice exposed in utero to carbofuran or diazinon: I. Changes in serum immunoglobulin concentrations.

Pregnant F2 dihybrid mice received either a vehicle-control or 1 of 2 doses of the anticholinesterase pesticides Carbofuran (0.01 or 0.50 mg/kg) or Diazinon (0.18 or 9.00 mg/kg) in the diet daily throughout gestation. All mothers gave birth to viable, overtly normal offspring at term. However, a significant number (12%) of pups born to dams who received 9.00 mg/kg Diazinon died prior to weaning on day 28; necropsy findings were consistent with death from respiratory infection. There was no significant difference in mortality between control and pesticide-exposed offspring once they reached 28 days of age. Determinations of 5 different classes of serum immunoglobulin (Ig) concentrations (IgG1,IgG2a,IgG2b, IgA, IgM) at 101, 400 and 800 days of age indicated transient but consistent disturbances of 2 Ig classes in offspring as a result of prenatal pesticide exposure. IgG1 concentrations of male offspring exposed to 0.50 mg/kg Carbofuran or 0.18 mg/kg Diazinon were significantly elevated at 101 days but not at 400 or 800 days of age. IgG1 concentrations of female offspring exposed to 0.01 mg/kg Carbofuran or 9.00 mg/kg Diazinon were significantly depressed at 101 days but not different from controls at 400 or 800 days of age. Changes in IgG2b levels generally were similar to those recorded for IgG1 but of smaller magnitude. There were no significant effects on serum IgG2b or IgM concentrations, and only equivocal effects on IgA, as a consequence of prenatal exposure to either pesticide.

Postnatal endocrine dysfunction resulting from prenatal exposure to carbofuran, diazinon or chlordane.

Prenatal exposure to pesticides of three different classes initiated persistent postnatal endocrine dysfunction. Adrenal function and hepatic metabolism of corticosterone were studied in adult hybrid mice exposed during development to either an organophosphate (Diazinon), a carbamate (Carbofuran), or an organochlorine (Chlordane). Animals were exposed to relatively low levels of the toxins in utero and neonatally via the mothers' milk. Exposure to lower doses of the anticholinesterase compounds, Diazinon or Carbofuran, resulted in impairment of hepatic metabolism of corticosterone in vitro due to a loss in reductive capacity per unit liver weight. Plasma levels of corticosterone were also elevated in these animals, but without a concomitant increase in adrenal steroidogenesis in vitro. The effects of exposure to Chlordane were more complex. In male animals, exposure to lower doses of chlordane resulted in an increase in plasma corticosterone levels without an apparent increase in hepatic metabolism of corticosterone or adrenal steroidogenesis. In contrast, side-chain metabolism of corticosterone was decreased in female mice exposed to Chlordane. Similar effects on pituitary-adrenal function were not evident for the offspring of mice exposed to higher doses of the toxins. Possible mechanisms for this non-linear dose-response are discussed.