Ann de Peyster

Cholinesterase and Self-reported Pesticide Exposure among Pregnant Women

Ascertainment of exposure to cholinesterase-inhibiting pesticides in pregnant subjects is complicated by altered enzyme activity that results from metabolic changes associated with pregnancy. Nevertheless, this study found a high correlation (Pearson chi-square = 13.67, p = .008) between classification of pesticide exposure using self-reported interview information and plasma cholinesterase activity for 203 pregnant women for whom three trimester cholinesterase values were available. All plasma cholinesterase activity values were referenced, by trimester, to a larger sample of 1,050 plasma cholinesterase values from 535 pregnant women. Subjects who lived nearest to agricultural land and who reported that they worked with pesticides in agricultural and other occupations tended to have lower plasma cholinesterase activity than those who reported use of household pesticides only.

Genetic toxicity studies of gossypol

Gossypol, a polyphenolic compound extracted from cotton plants, shows promise for use as a male contraceptive, as well as a treatment for gynecological disorders, cancer, and certain microbial diseases. Before gossypol can be considered safe for widespread human use, particularly by healthy people of childbearing age, its effect on normal genetic processes should be understood. Characterization of gossypols genotoxic potential has not been approached systematically, although numerous clinical and laboratory studies have addressed issues relating to genetic effects of gossypol. This review summarizes results of relevant studies and offers recommendations for the emphasis of future efforts to understand gossypols genotoxicity potential. Evidence suggesting that gossypol has any genotoxic effects in mammals under normal physiologic conditions so far is weak, at best. However, several unresolved issues that are important for establishing long-term genetic safety of gossypol were uncovered by this analysis. These include the need for a better understanding of the significance of weak increases in SCE frequency seen in a number of laboratory exposure studies, and more definitive, comprehensive animal tumor bioassay data.

Reduction of secondary smoke exposure in asthmatic children : parent counseling

Epidemiological evidence shows that childrens exposure to secondhand tobacco smoke increases their risk of respiratory illness. This study evaluated five families and their asthmatic children (aged 5-14 years) in an outpatient counseling program for reducing the childrens exposure to passive smoking. Intervention included biweekly counseling/instructions for parents to limit their childrens tobacco exposure. A multiple-baseline, quasiexperimental design was used for self-reported measures of the childrens smoke exposure and the parents smoking frequency. Counseling was associated with smoke exposure reduction of 40-80% from baseline for each of 5 children, with most improvements sustained during follow-up. This study provides support for the development of tobacco exposure prevention programs for children with pulmonary disease.

Hypothesis Testing with Values below Detection Limit in Environmental Studies.

Values below a specified detection limit are a common occurrence in environmental measurement which complicates statistical analysis. Thus paper addresses the problem of how these data may be included in hypothesis testing and demonstrates a solution that uses a regression model in the SAS statistical package with the ability to accommodate left-censored data. To illustrate, the LIFER- EG procedure is applied to data for an analyte (tin) found in fish tissue during a multifactorial bioaccumulation study involving two experimental sites, three experiments at each site, and sampling on multiple days. The results of this analysis are presented, indicating evidence of bioaccumulation but no significant differences between sites or experiments

Arsenic Levels in Hair of Workers in a Semiconductor Fabrication Facility

This study examined the relationship between total arsenic levels in hair of employees in a semiconductor fabrication facility and job responsibility, a surrogate variable for arsenic exposure potential. Maintenance personnel who regularly worked in equipment cleaning areas were assumed to have higher potential for occupational exposure than other employees. Occipital scalp hair samples were collected from 30 maintenance personnel, supervisors, and equipment engineers with high, medium, and low potential for exposure and from 26 administrative employees. Total arsenic in hair was measured by atomic absorption spectroscopy with hydride generation. Workplace air and wipe samples were analyzed to verify differing exposure potential in fabrication and administrative areas. Subjects completed written questionnaires to identify possible nonoccupational sources of arsenic. Mean hair arsenic in two of the three groups working in or near fabrication areas was slightly higher but not statistically different from that of administrative controls. Eliminating smokers, only the maintenance group regularly assigned to fabrication areas was higher than administrative controls but still not statistically different. A regression analysis of all factors indicated that sex, tapwater consumption, and dietary habits were significant contributors to arsenic in hair. Trends among these groups were consistent with expected exposure potential, although not dramatically different from controls. Main study conclusions were that (1) nonoccupational sources of arsenic can be expected to contribute more to hair levels in employees than that observed in this particular semiconductor work environment, where safe work practices were believed to be followed; and (2) monitoring should be considered in this industry to identify employees experiencing chronic, low-level arsenic exposures only if the facility also examines nonoccupational sources of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholinesterase Activity in Pregnant Women and Newborns

Plasma and red blood cell cholinesterase activity in blood samples from 259 pregnant women and cord blood from some of their newborn were compared with samples from 25 nonpregnant female volunteers and with laboratory norms (Ellman method). Plasma cholinesterase was significantly lower (p < 0.05) and red blood cell cholinesterase higher (p < 0.05) in pregnant women than in nonpregnant controls in a repeated measures analysis. By the sixth post-partum week, both plasma and red blood cell cholinesterase were similar to nonpregnant control activity. Fetal cord red blood cell cholinesterase activity was also lower than in nonpregnant women, but plasma levels were not significantly different. When compared with standard laboratory normal ranges, most (98-100%) plasma cholinesterase values in pregnant women and newborn were within range, whereas the majority (59-87%, depending on trimester) of red blood cell levels were above range in pregnancy and below range in 53% of newborns. A low red blood cell cholinesterase in pregnant women is more consistent with a possible overexposure to anticholinesterases than a low plasma cholinesterase. Periods of altered sensitivity to specific cholinesterase inhibiting drugs and environmental agents are suggested by these findings.

Ethyl t-butyl ether: review of reproductive and developmental toxicity.

Ethyl t-butyl ether (ETBE) is a motor fuel oxygenate used in reformulated gasoline. Knowledge of developmental and reproductive toxicity potential of ETBE is critical for making informed decisions about acceptance and regulations. This review discusses toxicology studies providing information about effects on reproduction and the conceptus. Seven GLP-compliant studies following widely accepted protocols have focused specifically on developmental and reproductive toxicity (DART) in rats and rabbits exposed to ETBE by gavage with doses up to 1,000 mg/kg body weight/day, the limit specified in standardized test guidelines. Other repeat-dose general toxicology studies have administered ETBE to rodents for up to 180 days, and included reproductive organ weights, histology, or other indications of reproductive system structure or function. DART potential of the main ETBE metabolite t-butyl alcohol and class-related MTBE has also been studied. More GLP-compliant studies exist for evaluating ETBE using well-established, currently recommended protocols than are available for many other chemicals used today. The database for determining ETBE DART potential is adequate, although not all study details are currently easily accessible for peer-review. ETBE does not appear to be selectively toxic to reproduction or embryofetal development in the absence of other manifestations of general toxicity. Studies using recommended methods for sample preservation and analysis have shown no targeted effect on the reproductive system. No embryofetal effects were observed in rabbits. Early postnatal rat pup deaths show no clear dose-response and have largely been attributed to total litter losses with accompanying evidence of maternal neglect or frank maternal morbidity.

Hypothesis-driven weight of evidence analysis to determine potential endocrine activity of MTBE

Endocrine-related endpoints in animals have been reported to respond to high doses of methyl tertiary-butyl ether (MTBE), however, a systematic and transparent evaluation of endocrine potential has not been published. Resolving whether MTBE exhibits endocrine activity is important given regulatory and public interest in endocrine disrupting substances and their potential for causing adverse effects in humans or wildlife. A weight-of-evidence (WoE) analysis was conducted, focusing on hypotheses related to the potential for MTBE to interact with estrogen, androgen, and thyroid pathways, and steroidogenesis. To reach scientifically justified conclusions based on the totality of evidence, this WoE procedure involved a semi-quantitative relevance weighting of each endpoint for each hypothesis and systematic consideration of each endpoint in various study designs. This procedure maximized use of an extensive body of relevant and reliable literature on MTBE with evidence supporting or opposing a given mode of action hypothesis. Evaluating the strength and consistency of observations from many MTBE studies also provided a way to assess whether high doses used in experiments with MTBE confound identification of direct endocrine system responses. Based on results of studies using mammalian and fish models and in vitro screening assays, this WoE assessment reveals that MTBE lacks direct endocrine activity.

Effect of ETBE on reproductive steroids in male rats and rat Leydig cell cultures

These experiments were conducted to follow up on a report of testis seminiferous tubular degeneration in Fischer 344 rats treated with high doses of ethyl t-butyl ether (ETBE). Also, high doses of a related compound, methyl t-butyl ether (MTBE), had been shown to reduce circulating testosterone (T) in rats. Isolated rat Leydig cells were used to compare hCG-stimulated T production following exposure to ETBE, MTBE, and their common main metabolite, TBA. In addition, male Fischer 344 rats were gavaged daily with 600 mg/kg, 1200 mg/kg or 1800 mg/kg ETBE in corn oil (n=12) for 14 days, the 1200 mg/kg dose chosen for comparison with a prior 14-day MTBE gavage experiment. In cell culture experiments, TBA was more potent than either ETBE or MTBE, both of which caused similar inhibition of T production at equimolar concentrations. In the in vivo study, no significant plasma T reduction was seen 1h after the final 1200 mg/kg ETBE dose, whereas 1200 mg/kg MTBE had significantly lowered T when administered similarly to Sprague-Dawley rats. Some rats treated with 1800 mg/kg ETBE had noticeably lower T levels, and the group average T level was 66% of corn oil vehicle control (p>0.05) with high variability also evident in ETBE-treated rats. 17beta-Estradiol had been increased by 1200 mg/kg MTBE, and was elevated in the 1200 and 1800 mg/kg ETBE dose groups (p<0.05), both groups also experiencing significantly reduced body weight gain. None of these effects were seen with 600 mg/kg/day ETBE. No definitive evidence of androgen insufficiency was seen in accessory organ weights, and no testicular pathology was observed after 14 days in a small subset of 1800 mg/kg ETBE-treated animals. Like MTBE, ETBE appears to be capable of altering reproductive steroid levels in peripheral blood sampled 1h after treatment, but only with extremely high doses that inhibit body weight gain and may produce mortality.

Fathead minnow optomotor response as a behavioral endpoint in aquatic toxicity testing

Fish behavior tests have long been recognized as good indicators of sublethal levels of toxicants in water (Kleerekoper 1976; Marcucella and Abramson 1978; Rand 1985). Endpoints being developed for use in controlled laboratory studies include swimming behavior, chemoreception, spontaneous locomotor activity, ventilatory behavior, and preferenceavoidance. Here we report an evaluation of an optomotor response test in fathead minnows (Pimephales promelas) as a behavioral toxicity assay for the laboratory. The goal of these experiments was to determine whether optomotor response measurements might be suitable for use with these fish, either in effluent biomonitoring programs or for establishing maximum allowable contaminant levels (e.g., MATCs) for specific pollutants.