Derivation of an occupational exposure limit for benzene using epidemiological study quality assessment tools.

This paper derives an occupational exposure limit for benzene using quality assessed data. Seventy-seven genotoxicity and 36 haematotoxicity studies in workers were scored for study quality with an adapted tool based on that of Vlaanderen et al., 2008 (Environ Health. Perspect. 116 1700-5). These endpoints were selected as they are the most sensitive and relevant to the proposed mode of action (MOA) and protecting against these will protect against benzene carcinogenicity. Lowest and No- Adverse Effect Concentrations (LOAECs and NOAECs) were derived from the highest quality studies (i.e. those ranked in the top tertile or top half) and further assessed as being "more certain" or "less certain". Several sensitivity analyses were conducted to assess whether alternative "high quality" constructs affected conclusions. The lowest haematotoxicity LOAECs showed effects near 2 ppm (8 h TWA), and no effects at 0.59 ppm. For genotoxicity, studies also showed effects near 2 ppm and showed no effects at about 0.69 ppm. Several sensitivity analyses supported these observations. These data define a benzene LOAEC of 2 ppm (8 h TWA) and a NOAEC of 0.5 ppm (8 h TWA). Allowing for possible subclinical effects in bone marrow not apparent in studies of peripheral blood endpoints, an OEL of 0.25 ppm (8 h TWA) is proposed.

Chronic physical effects and health care utilization in long-term ovarian germ cell tumor survivors: a Gynecologic Oncology Group study.

PURPOSE: This study compares late effects of treatment on physical well-being and utilization of health care resources between ovarian germ cell tumor (OGCT) survivors and age/race/education-matched controls. PATIENTS AND METHODS: Eligible patients had OGCT treated with surgery and chemotherapy and were disease-free for at least 2 years at time of enrollment. The matched control group was selected from acquaintances recommended by survivors. Symptoms and function were measured using previously validated scales. Health care utilization was assessed by questions regarding health insurance coverage and health services utilization. RESULTS: One hundred thirty-two survivors and 137 controls completed the study. Survivors were significantly more likely to report a diagnosis of hypertension (17% v 8%, P = .02), and marginally hypercholesterolemia (9.8% v 4.4%, P = .09), and hearing loss (5.3% v 1.5%, P = .09) compared with controls. There were no significant differences in the rates of self-reported arthritis, heart, pulmonary or kidney disease, diabetes, non-OGCT malignancies, anxiety, hearing loss, or eating disorders between groups. Among chronic functional problems, numbness, tinnitus, nausea elicited by reminders of chemotherapy (v general nausea triggers for controls), and Raynaud's symptoms were reported more frequently by survivors. Patients who received vincristine, dactinomycin, and cyclophosphamide in addition to cisplatin therapy had increased functional complaints, particularly numbness and nausea. Health care utilization was similar, but 15.9% of survivors reported being denied health insurance versus 4.4% of controls (P < .001). CONCLUSION: Although a few sequelae of treatment persist, in general, OGCT survivors enjoy a healthy life comparable to that of controls.