Building shared experience to advance practical application of pathway-based toxicology: liver toxicity mode-of-action.

A workshop sponsored by the Human Toxicology Project Consortium (HTPC), "Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action" brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is extremely helpful. In addition, it is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered.

Prenatal exposure to ß2-adrenergic receptor agonists and risk of autism spectrum disorders.

This study aims to investigate the association between prenatal exposure to terbutaline and other ß2 adrenergic receptor (B2AR) agonists and autism spectrum disorders (ASDs). The methodology used is a case-control study among children born from 1995 to 1999 at Kaiser Permanente Northern California hospitals. Cases (n = 291) were children with an ASD diagnosis; controls (n = 284) were children without ASDs, randomly sampled and frequency-matched to cases on sex, birth year, and delivery hospital. Exposure to B2AR agonists during 30 days prior to conception and each trimester of pregnancy was ascertained from prenatal medical records and health plan databases. The frequency of exposure to any B2AR agonist during pregnancy was similar for mothers of children with ASD and mothers of controls (18.9% vs. 14.8%, P = 0.19). Exposure to B2AR agonists other than terbutaline was not associated with an increased risk for ASDs. However, terbutaline exposure for >2 days during the third trimester was associated with more than a fourfold increased risk for ASDs independent of indication although the limited sample size resulted in an imprecise and nonsignificant effect estimate (OR(adj) = 4.4; 95% confidence interval, 0.8-24.6). This analysis does not offer evidence linking B2AR exposure in pregnancy with autism risk. However, exposure to terbutaline during the third trimester for >2 days may be associated with an increased risk of autism. Should this result be confirmed in larger samples, it would point to late pregnancy as an etiologic window of interest in autism risk factor research.

Maternal Rh D status, anti-D immune globulin exposure during pregnancy, and risk of autism spectrum disorders.

OBJECTIVE: The objective of the study was to investigate the association between maternal Rh D status, prenatal exposure to anti-D immune globulin, and the risk of autism in the offspring. STUDY DESIGN: Case-control study among children born from 1995 to 1999 at Kaiser Permanente Northern California hospitals. Cases (n = 400) were children with an autism diagnosis; controls (n = 410) were children without autism, randomly sampled and frequency matched to cases on sex, birth year, and birth hospital. Maternal Rh D status and anti-D immune globulin exposure were ascertained from prenatal medical records. RESULTS: No case-control differences were observed for maternal Rh negative status (11.5% vs 10.0%, P = .5) or prenatal anti-D immune globulin exposure (10.0% vs. 9.3%, P = .7). Risk of autism remained unassociated with maternal Rh status or prenatal exposure to anti-D immune globulins after adjustment for covariates. CONCLUSION: These data support previous findings that prenatal exposure to thimerosal-containing anti-D immune globulins does not increase the risk of autism.

Cigar and smokeless tobacco use in the lesbian, gay, and bisexual population.

Large population-based studies of alternative tobacco use in the lesbian, gay, and bisexual (LGB) population are needed to more fully measure tobacco use outcomes. This descriptive study used standard measures of alternative tobacco use from two separate, statewide household-based studies to compare basic prevalence rates in the LGB population and the general population in California. A total of 1,950 adult lesbians, bisexual women, heterosexual women who have sex with women, gay men, bisexual men, and heterosexual men who have sex with men, all living in California, completed surveys between 2003 and 2004. From a general population-based sample (California Tobacco Survey, 2002), a total of 11,037 adult women and 9,488 men were used as comparisons. The prevalence rates for lifetime and current cigar smoking and smokeless tobacco use were lower for all LGB subpopulations compared with the general population.

Disparities in smoking between the lesbian, gay, and bisexual population and the general population in California.

OBJECTIVES: We conducted a large, population-based study to assess tobacco use in California's lesbian, gay, and bisexual (LGB) population. METHODS: Standard measures of tobacco use from 2 separate, statewide household-based studies were used to compare basic prevalence rates in the LGB population and the general population in California. Data were derived from a 2003-2004 survey of LGB individuals living in California as well as from the 2002 version of the California Tobacco Survey, which gathered data on the state's general population. RESULTS: Smoking prevalence rates were higher in our sample of lesbians, bisexual women, and women who have sex with women than among women in the general California population. In the case of men, the only significant difference was that rates were higher among gay men than among men in the general population. Disparities in tobacco use between the LGB population and the general population were still evident after we controlled for key demographic variables and in comparisons with other tobacco use indicators such as average cigarette consumption. CONCLUSIONS: Tobacco control efforts targeting the LGB population are needed to reduce this group's high rate of cigarette smoking.

Detection of intimate-partner violence among members of a managed behavioral health organization.

This column describes a creative effort on the part of a national behavioral managed care plan to identify cases of domestic violence in its covered population. Although the screening efforts by intake counselors and clinicians yielded a lower rate of domestic violence than would have been expected, the effort established a baseline or benchmark from which the organization can now work. Clinical benchmarks are critical to developing an understanding of best practices. In this case, the benchmark finding initiated a best practices process through which this organization--and, hopefully, others--will continue to create better methods for identifying and helping people who experience domestic violence.