Abstract  A 6-week-old breast-fed infant had obstructive jaundice and hepatomegaly. When a dry-cleaning solvent, tetrachloroethylene, was detected in the mother's milk and blood, breast-feeding was discontinued. Rapid clinical and biochemical improvement followed. The child grew normally and had normal liver function during 2 years of follow-up.

Abstract  Human subjects were exposed to tetrachloroethene (perchloroethylene, PER). The duration of exposure ranged from one to 60 minutes and the concentration of PER in inhaled air ranged from 0.02 to 0.40 mmol/m3. Alveolar air was sampled after several residence times (t*) in the lung. Both during and after exposure, the concentration of PER in alveolar air (C Alv) as a function of the residence time was studied to estimate the concentration in the pulmonary artery (C Ven: mixed venous blood) and in the pulmonary vein (C Art: arterial blood). During exposure C Alv decreased as function of t*. At t* = 10 s C Alv was 70-75% of the value presented at t* = 5 s; this decrease approximates an exponential curve. C Alv seemed to stabilise at t* = 10-12 s, whereas it decreased more rapidly at t* greater than 12 s; this decrease continued up to at least t* = 55 s when C Alv was about 40% of the value it represented at t* = 5 s. In the postexposure period C Alv increased as function of t* from 5 to 10 s. Both during and after exposure, no difference was observed between C Alv at t* = 10 s and C Alv in the exhaled part of the expiratory reserve volume. A simple gas exchange model showed that the decrease or increase of C Alv at t* less than 10 s could be explained by either absorption or excretion by mixed venous blood. C Alv at t* = 10-12 s provided a valid estimate of C Ven. To estimate C Art, its fluctuating character due to the discontinuous breathing with a breathing frequency had to be taken into account. It is shown that C Alv during normal breathing (t* = 5 s) provides a reasonable estimate of the time weighted concentration in arterial blood

Abstract  In 2000, the Agency for Toxic Substances and Disease Registry (ATSDR) released a report concerning elevated autism prevalence and the presence water chlorination byproducts in the municipal drinking water supply in Brick Township, New Jersey. The ATSDR concluded that it was unlikely that these chemicals, specifically chloroform, bromoform (Trihalomethanes; THMs) and tetrachloroethylene (Perchloroethylene; PCE) had contributed to the prevalence of autism in this community based upon correlations between timing of exposure and/or concentration of exposure. The ATSDR conclusion may have been premature, as there is no conclusive data evidencing a correlation between a particular developmental time point that would render an individual most susceptible to toxicological insult with the development of autism. Therefore, it was our aim to determine if these chemicals could contribute to autistic like behaviors. We found that males treated with THMs and PCE have a significant reduction in the number of ultrasonic vocalizations (USVs) emitted in response to maternal separation, which are not attributed to deficits in vocal ability to or to lesser maternal care. These same males also show significantly elevated anxiety, an increase in perseverance behavior and a significant reduction in sociability. The sum of our data suggests that male, but not female mice, develop autistic like behaviors after gestational and postnatal exposure to the aforementioned chemical triad via drinking water. We believe development of such aberrant behaviors likely involves GABAergic system development.

Abstract  BACKGROUND: There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants; however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk.

PROCEDURE: We conducted a case-only study to evaluate census tract-level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children's Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the US EPA's 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case-only odds ratios and 95% confidence intervals (CIs).

RESULTS: There were 11 significant gene-environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04).

CONCLUSIONS: This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies.

Abstract  This report describes follow-up evaluations of adults and children who may have been exposed to perchloroethylene (perc) while working at or attending the Pumpkin Patch Day Care Center (PPDCC) in Guilderland, NY. Evaluation of adults involved assessment of visual contrast sensitivity (VCS) and color vision. Evaluation of children included a thorough neurobehavioral assessment as well as assessment of VCS and color vision. In August 1998 the New York State Department of Health (NYSDOH), the Albany County Health Department, and the U.S. Centers for Disease Control (U.S. CDC) conducted an investigation at the PPDCC. At the time of this original investigation a dry cleaner using perc was operating adjacent to the PPDCC and elevated air levels of perc (1,800 – 2,400 ug/m3) were detected in classrooms. All employees and parents or guardians of children attending the daycare center were notified, the dry cleaner voluntarily ceased using perc at that location, and perc levels quickly decreased to background levels. Because exposure to elevated levels of perc may have adverse effects on visual or central nervous system (CNS) function, visual function and CNS function were evaluated in PPDCC employees and children attending the PPDCC, respectively. CNS function was assessed in 18 four- and five-year-old PPDCC children and 24 age- and gender-matched control children. Visual function was assessed in nine PPDCC employees and in nine adults not exposed to perc using tests of visual contrast sensitivity (VCS) and color vision. Children were not given VCS or color vision tests because they were too young to perform them at the time of the original investigation; adults were not given CNS function tests since the tests available were appropriate for children only. No deficits in CNS function were detected in the PPDCC children. Employees had a small deficit in VCS compared to the group of adults not exposed to perc, although performance of both groups was within the normal range. A small difference in color vision between PPDCC employees and the adults not exposed to perc was noted, but the difference was not statistically significant. These findings were summarized in draft and final reports (NYSDOH 1999; 2005). In the final report, NYSDOH noted that follow-up evaluations of PPDCC employees and children would be completed to assess whether there were long term effects on vision among employees and/or long term effects on vision and/or neurobehavioral function among children (NYSDOH 2005). During the original investigation, PPDCC employees and parents or guardians of children who attended the PPDCC prior to discovery of perc in August 1998 were invited to enroll in the New York State (NYS) Volatile Organic Compounds (VOC) Exposure Registry. All PPDCC employees enrolled in the NYS VOC Exposure Registry (n=25) were asked to participate in the adult follow-up evaluation which involved completing a comprehensive ophthalmologic exam and VCS and color vision tests at a local ophthalmology clinic. A subset of the 115 children enrolled in the NYS VOC Exposure Registry who had spent the most time at the PPDCC prior to August 8, 1998 were asked to participate in the child follow-up evaluation (n=28). This subset of children was asked to participate since the likelihood of detecting effects associated with perc exposure, if they existed, would be greatest in these children. Children participating in the follow-up evaluation were asked to complete a comprehensive ophthalmologic exam and VCS and color vision tests at a local ophthalmology clinic. They were also asked to complete a comprehensive neurobehavioral evaluation at a local neuropsychology clinic. Another group of age- and gender-matched children who had attended other daycare centers were asked to participate as a comparison group in the child follow-up evaluation. Twelve of 25 PPDCC adult employees in the NYS VOC Exposure Registry agreed to participate in the follow-up evaluation and were scheduled for an ophthalmologic exam and VCS and color vision tests. Five of the 12 employees kept their scheduled appointments; four of these employees had participated in the original PPDCC investigation. Color vision was normal for all five adults. VCS at the highest spatial frequencies was below normal for two adults. However, both of these adults had ophthalmologic conditions (cataract, astigmatism) known to cause this effect. The other three adults had normal VCS. Strong conclusions cannot be drawn from the small number of employees who were evaluated and applied to others who may have been similarly exposed to perc. However, for the employees who participated, this follow-up evaluation showed that color vision was normal; and that VCS was normal as long as no other eye conditions were present that are known to lower it. Parents or guardians of 28 children in the NYS VOC Exposure Registry were asked to have their child (children) participate in the follow-up evaluation. Twenty children agreed to participate; 17 completed vision testing; and 13 completed some or all neurobehavioral testing. Seventeen other children, matched for age and gender to participating PPDCC children, were enrolled as comparison children. Thirteen comparison children completed vision testing and a slightly different group of 13 children completed neurobehavioral testing. Comparisons for matched pairs were performed to assess whether VCS or color vision in PPDCC children differed from comparison children. Four of the 17 PPDCC children completing vision testing were not matched to comparison children, and their VCS and color vision was evaluated qualitatively. Unmatched group comparisons were performed to assess whether neurobehavioral function in the 13 PPDCC children tested differed from the 13 comparison children tested. This was because only eight specifically age- and gender-matched pairs completed neurobehavioral testing. Neurobehavioral performance of PPDCC and comparison children was also compared to published normative ranges. As a group, PPDCC children performed no worse than comparison children on the VCS or color vision tests. In fact, on the VCS test PPDCC children performed better than comparison children. Both PPDCC and comparison children performed within normative ranges for the neurobehavioral functions evaluated. Group comparisons also indicated that PPDCC children performed no worse than comparison children on neurobehavioral tests, and on some of these tests performed better. These findings suggest no long term effect on visual function (measured with VCS and color vision) or neurobehavioral function among children who were exposed to perc (1,800 to 2,400 ug/m3) for about three years while attending the PPDCC during their preschool years. The subset of PPDCC children evaluated represent children who spent the most time at the PPDCC prior to August 8, 1998 and therefore may have had the greatest potential exposures to perc. These children are therefore the most likely to have exhibited long-term effects due to perc if they were present. Based on the findings of this follow-up evaluation showing no noticeable effects among these children, it is unlikely that an effect on VCS, color vision, or neurobehavioral function would be detected in other children who attended the PPDCC.

Abstract  To study the role of tobacco smoking and alcohol drinking in the etiology of non-Hodgkin's lymphoma (NHL), we conducted a multicenter case-control study in Spain, France, Germany, Italy, Ireland and Czech Republic between 1998 and 2004, which included 1,742 cases of NHL and 2,465 controls matched on age, sex and recruitment area. Tobacco smoking was not associated with the risk of NHL overall or with risk of specific histological subtypes. Similarly, there was no association between alcohol drinking and the risk of NHL overall or across histological subtypes. However, a protective effect of alcohol drinking was observed among men (OR = 0.76, 95% CI = 0.62-0.93) and in non-Mediterranean countries (OR = 0.73, 95% CI = 0.61-0.86). There was no evidence of interaction between alcohol drinking and tobacco smoking in NHL etiology. The results of this large-scale European study did not support an association between tobacco and NHL and suggested a protective effect of alcohol on development of NHL for men and in non-Mediterranean countries.