Studies in adaption to ambient oxidant air pollution: effects of ozone exposure in Los Angeles residents vs. new arrivals. (49/8052)

To test the hypothesis that adaptation protecting against acute effects of ambient ozone (O3) exposures develops in Los Angeles residents, human volunteers were exposed to 0.4 ppm O3 under conditions simulating ambient pollution exposures. Blood biochemical, pulmonary physiological, and clinical responses were assessed. Los Angeles residents (N = 6) showed only minimal clinical or physiological response to O3, while new arrivals (N = 9) showed significant losses in pulmonary function and a tendency toward increased symptoms. Most biochemical responses did not differ significantly between residents and new arrivals. These results agree with others in suggesting that exposures to elevated ambient concentrations of O3 produce adaptation in a least some residents of photochemical pollution areas. The underlying mechanisms and long-term consequences of such adaptation are unknown.  (+info)

Behavioral testing as a method for assessing risk. (50/8052)

Behavioral effects have been found to result from the prenatal administration of substances known to be teratogenic to the CNS. These effects occur at dose levels lower than those producing gross malformations and when the agent is administered at times other than that optimal for CNS relevant technique for detecting adverse consequences of prenatal exposure to drugs and chemicals. Behavioral testing, however, also appears to have attributes that dictate a thoughtful approach to its role as a method for assessing risk, and additional research is needed to obtain usable techniques. The need for such research is intensified by the present inability to identify potential behavioral teratogens by means other than laboratory investigation.  (+info)

Research strategies for behavioral teratology studies. (51/8052)

Several compelling aruguments have been advanced in support of expanding the use of "behavioral teratology" evaluations as routine components of toxicologic screening procedures. As a basis for development of effective behavioral teratology screening approaches, a conceptual framework is presented which interrelates: (1) changes in relative functional brain capacity with age, (2) possible times and durations of exposures to environmental insults, and (3) various types of toxicity testing procedures carried out at appropriate time points in relation to different exposure period. Within the context, several research strategies for behavioral teratology studies are concisely posed and evaluated. These include: (1) clinical hypothesis testing, where particular effect(s) of a given agent are evaluated based on hypotheses derived from clinical or epidemiological observations; (2) comprehensive screening approaches, where multifaceted, long-term longitudinal neurobehavioral evaluations are employed to assess whether any of a large number of possible deletarious effects are exerted by an agent and at what threshold exposure levels; (3) alternative screening heuristics, by which adequate assessments of neurobehavioral toxicity of various agents may be accomplished without completion of more exhaustive, but also more expensive and time-consuming comprehensive screening protocols.  (+info)

Assessment of current test procedures. (52/8052)

The belief that screening tests for teratogenicity are of low predictive value has many supporters who point to the inconsistency with which malformations are induced. However, to fault the test systems when such inconsistency is predictable from both the inherently unstable nature of a malformation and from fundamental principles of teratology, is unrealistic, and, as is shown, perhaps the greater faults lie with the critics. It is suggested by examples that, if attention was concentrated not on the inconsistent malformations but on more consistent embryopathic effects which in one form or another are always associated with malformations, the predictive value of the screening tests would appear in a more favorable light. Thus, even if malformations are not demonstrated, the range of conditions (dosages) in which they might occur can be determined. Such information, used in conjunction with that obtained from other preclinical studies, can then form a reasonably sound basis for extrapolation to man.  (+info)

Study of environmental, social, and paternal factors in preterm delivery using sibs and half sibs. A population-based study in Denmark. (53/8052)

OBJECTIVE: The aim of this study was to evaluate the influence on preterm delivery of changes in putative genetic and environmental risk factors between two consecutive births. Low social status is a suspected risk indicator of preterm delivery, but the impact of social mobility has not been studied before. PARTICIPANTS: The study uses national cohorts in which women act as their own controls. Subjects were identified by means of registries: 10,455 women who gave birth to a preterm child and had a subsequent live birth between 1980 and 1992 and 9849 women who gave birth to a child after 37 completed weeks of gestation and had a subsequent live born child in the same time period formed the cohorts. METHODS: The risk of having a premature infant in the subsequent pregnancy was analysed in each cohort as a function of changes in male partner, residency, occupation, and social status between the two pregnancies. RESULTS: There was a strong tendency to repeat a preterm delivery (18% v 6% in the general population). Social decline was associated with a moderate increase in the recurrence risk (OR: 1.22; 95% CI: 1.02, 1.47). In the reference cohort the risk of preterm delivery associated with changing from a rural to an urban municipality was 2.03 (95% CI: 1.14, 3.64). CONCLUSIONS: Social decline and moving to an urban municipality may be associated with preterm delivery.  (+info)

Calculating the interindividual geometric standard deviation for use in the integrated exposure uptake biokinetic model for lead in children. (54/8052)

The integrated exposure uptake biokinetic (IEUBK) model, recommended for use by the U.S. Environmental Protection Agency at residential Superfund sites to predict potential risks to children from lead exposure and to establish lead remediation levels, requires an interindividual geometric standard deviation (GSDi) as an essential input parameter. The GSDi quantifies the variability of blood lead concentrations for children exposed to similar environmental concentrations of lead. Estimates of potential risks are directly related to the GSDi, and therefore the GSDi directly impacts the scope of remediation at Superfund sites. Site-specific GSDi can be calculated for sites where blood lead and environmental lead have been measured. This paper uses data from blood and environmental lead studies conducted at the Bingham Creek and Sandy, Utah, Superfund sites to calculate GSDi using regression modeling, box modeling, and structural equation modeling. GSDis were calculated using various methods for treating values below the analytical method detection and quantitation limits. Treatment of nonquantifiable blood lead concentrations affected the GSDi more than the statistical method used to calculate the GSDi. For any given treatment, the different statistical methods produced similar GSDis. Because of the uncertainties associated with data in the blood lead studies, we recommend that a range of GSDis be used when analyzing site-specific risks associated with exposure to environmental lead instead of a single estimate. Because the different statistical methods produce similar GSDis, we recommend a simple procedure to calculate site-specific GSDi from a scientifically sound blood and environmental lead study.  (+info)

Reactive airways dysfunction and systemic complaints after mass exposure to bromine. (55/8052)

Occasionally children are the victims of mass poisoning from an environmental contaminant that occurs due to an unexpected common point source of exposure. In many cases the contaminant is a widely used chemical generally considered to be safe. In the following case, members of a sports team visiting a community for an athletic event were exposed to chemicals while staying at a local motel. Bromine-based sanitizing agents and other chemicals such as hydrochloric acid, which were used in excess in the motel's swimming pool, may have accounted for symptoms experienced by the boy reported here and at least 16 other adolescents. Samples of pool water contained excess bromine (8.2 microg/mL; ideal pool bromine concentration is 2-4 microg/mL). Symptoms and signs attributable to bromine toxicity included irritative skin rashes; eye, nose, and throat irritation; bronchospasm; reduced exercise tolerance; fatigue; headache; gastrointestinal disturbances; and myalgias. While most of the victims recovered within a few days, the index case and several other adolescents had persistent or recurrent symptoms lasting weeks to months after the exposure.  (+info)

Trichloroethylene exposure and specific somatic mutations in patients with renal cell carcinoma. (56/8052)

BACKGROUND: The development of renal cell carcinoma (RCC) has been associated with both genetic and environmental factors-with mutations in the von Hippel-Lindau (VHL) tumor suppressor gene for clear-cell RCC specifically and with long-term exposure to high doses of trichloroethylene (TRI), an industrially important solvent, for RCC generally. We investigated whether TRI exposure produces RCC through a specific mutational effect on the VHL gene by analyzing VHL sequences in the RCCs of patients exposed to high, cumulative doses of TRI. METHODS: The level of exposure for each of 44 patients with RCC who had known industrial exposure to TRI was classified according to the duration, frequency, and mode of exposure. Samples of normal and cancerous tissues were microdissected from paraffin-embedded tissue. DNA was isolated from these samples, and somatic VHL mutations were identified by polymerase chain reaction analysis, single-strand conformation polymorphism analysis, DNA sequencing, and restriction enzyme digestion. Control samples included RCC DNA from 107 patients without known TRI exposure and lymphocyte DNA from 97 healthy subjects. RESULTS: RCCs of TRI-exposed patients showed somatic VHL mutations in 33 (75%) of 44 cases. The mutations were frequently multiple and accompanied by loss of heterozygosity, and there was an association between the number of mutations and the severity of TRI exposure. We observed a specific mutational hot spot at VHL nucleotide 454 in the RCCs of 13 (39%) of the patients, and this mutation was present in adjacent non-neoplastic kidney parenchyma in four of these patients. The nucleotide 454 mutation was neither detected in any of the RCCs from patients without TRI exposure nor in any of the healthy subjects. CONCLUSION: Our results suggest that RCC in patients with high, cumulative TRI exposure is associated with a unique mutation pattern in the VHL gene.  (+info)