Retrospective on U.S. Health Risk Assessment: How Others Can Benefit

Dr. Paustenbach reviews the scientific underpinnings of about twenty years of health risk assessment practice and their implications for environmental policy. He observes that more than 600 peer-reviewed papers provide a wealth of information that can save other countries billions of dollars. He also briefly reviews risk-assessment practices outside the U.S

Data on the histological and immune cell response in the popliteal lymph node in mice following exposure to metal particles and ions

AbstractHip implants containing cobalt–chromium (CoCr) have been used for over 80 years. In patients with metal-on-metal (MoM) hip implants, it has been suggested that wear debris particles may contribute to metal sensitization in some individuals, leading to adverse reactions. This article presents data from a study in which the popliteal lymph node assay (PLNA) was used to assess immune responses in mice treated with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3, and NiCl2) or Cr2O3 particles with metal salts (“A preliminary evaluation of immune stimulation following exposure to metal particles and ions using the mouse popliteal lymph node assay” (B.E. Tvermoes, K.M. Unice, B. Winans, M. Kovochich, E.S. Fung, W.V. Christian, E. Donovan, B.L. Finley, B.L. Kimber, I. Kimber, D.J. Paustenbach, 2016) [1]). Data are presented on (1) the chemical characterization of TiO2 particles (used as a particle control), (2) clinical observations in mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, (3) PLN weight and weight index (WI) in mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, (4) histological changes in PLNs of mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, (5) percentages of immune cells in the PLNs of mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts, and (6) percentages of proliferating cells in the PLNs of mice treated with Cr2O3 particles, metal salts or Cr2O3 particles with metal salts

Age- and Concentration-Dependent Elimination Half-Life of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Seveso Children

OBJECTIVE: Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents. DESIGN: We used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration and quantity in the body, severity of chloracne response, body mass index, and body fat mass. PARTICIPANTS: Blood was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18 years of age at the time of a nearby trichlorophenol reactor explosion in July 1976. RESULTS: TCDD half-life in persons < 18 years of age averaged 1.6 years while those ≥18 years of age averaged 3.2 years. Half-life is strongly associated with age, showing a cohort average increase of 0.12 year half-life per year of age or time since exposure. A significant concentration-dependency is also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for children < 12 years of age and 700 ppt when including adults. Moderate correlations are also observed between half-life and body mass index, body fat mass, TCDD mass, and chloracne response. CONCLUSIONS: Children and adolescents have shorter TCDD half-lives and a slower rate of increase in half-life than adults, and this effect is augmented at higher body burdens. RELEVANCE: Modeling of TCDD blood concentrations or body burden in humans should take into account the markedly shorter elimination half-life observed in children and adolescents and concentration-dependent effects observed in persons > 400–700 ppt

THE EFFECT OF THE TWELVE-HOUR WORKSHIFT ON THE TOXICOLOGY, DISPOSITION AND PHARMACOKINETICS OF CARBON TETRACHLORIDE IN THE RAT

Male Sprague-Dawley Rats were exposed in a closed-loop inhalation chamber to 100 ppm of (\u2714)C-CCl(,4) vapor for 8 hr/day for 10 of 12 days or 12 hr/day for 7 (4 + 3) of 12 days. Following one and two weeks of exposure to either the 8 hr/day or 12 hr/day dosing regimens, the fat, liver, lung and adrenals had the highest concentration of CCl(,4). The kidneys, spleen, brain, and heart contained 40-70% less CCl(,4) than that of the fat. Following each days exposure, the CCl(,4) concentration in the brain was significantly greater for the 12 hr/day group. Following a typical weekend off work, the fat contained 3-8 times more CCl(,4) than other organs. Histological damage was similar for either group following each week of exposure. However, the rats exposed for 12 hr/day had significantly higher sorbitol dehydrogenase (SDH) levels than the 8 hr/day groups. It was noted that the 12 hr/day dosage regimen produced differences in the relative rates and routes of elimination of CCl(,4) when compared with rats exposed 8 hr/day. Following two weeks of exposure to the 8 hr/day schedule, expired CCl(,4) and fecal (\u2714)C-activity comprised 45% and 48% respectively of the total (\u2714)C excreted. Following two weeks of exposure to the 12 hr/day dosing regimen, the values were 32% and 62%. In both cases, the urine accounted for less than 6% of the total (\u2714)C excreted and exhaled (\u2714)CO(,2) for 2% or less. Elimination of CCl(,4) in the expired air of the 8 hr group had an average fast phase ((alpha)) half-life of approximately 100 min and for the slow phase ((beta)), 450 min. For the 12 hr group, the half-lives were 90 min ((alpha)) and 635 min ((beta)). 80% of the total amount of expired CCl(,4) was eliminated within 6 hours. The average t(, 1/2) for urinary excretion was 1320 min and 3050 min and the average t(, 1/2) for elimination of (\u2714)CO(,2) in the expired air was 1700 min and 4250 min for the 8 hr and 12 hr groups, respectively. Rats exposed to the 12 hr/day dosing regimen had a greater percentage of CCl(,4) distributed to the feces and the fat than those exposed for 8 hr/day. The slow release of CCl(,4) from these peripheral compartments to the blood was reflected by the much longer half-lives of (\u2714)C elimination in the expired air and urine of rats exposed to the 12 hr/day schedule. This study suggests that adjustments to occupational exposure limits (TLVs and PELs) are necessary to protect workers exposed to extraordinary workshifts since a slight change in the work schedule has been shown to influence the distribution, toxicity and the pharmacokinetics of an inhaled toxicant

Radiological risk assessment of the Hunters Point Naval Shipyard (HPNS)

Hunters Point Naval Shipyard in San Francisco, California was deemed a Superfund site by the USEPA in 1989 due to chemical and radiological contamination resulting from U.S. Navy operations from 1939 to 1974. During characterization and remediation efforts, over 50,000 radiological soil samples and 19,000 air samples were collected. This risk assessment, conducted in accordance with federal guidelines, represents the first comprehensive evaluation of past, present, and future health risks associated with radionuclides present at the site. The assessment indicated that before site remediation, most radionuclide soil concentrations were at or near local background concentrations. Had such low remedial goals not been established, significant remediation of surface soils would not have been necessary to protect human health. The pre-remediation lifetime incremental cancer morbidity risks for on-site workers and theoretical on-site residents due to radionuclide contamination were found to be 1.3 × 10−6 and 3.2 × 10−6, respectively. The post-remediation risks to future on-site residents were found to be 6.3 × 10−8 (without durable cover) and 3.7 × 10−8 (with durable cover), while post-remediation risks to on-site workers were found to be 2.6 × 10−8 (without durable cover) and 1.6 × 10−8 (with durable cover). Risk estimates for all scenarios were found to be significantly below the acceptable risk of 3 × 10−4 approved by regulatory agencies. Upwind and downwind air samples collected during remediation indicate that remediation activities never posed a measurable risk to off-site residents. This risk assessment emphasizes the importance of establishing clear and scientifically rigorous soil remedial goals at sites as well as understanding local radionuclide background concentrations