Characterizing and controlling industrial dust: a case study in small particle measurement.

Instrumentation used to measure characteristics of fine particles entrained in gas or suspended in aerosols provides information needed to develop valid regulations for emission sources and to support the design of control technologies. This case study offers a brief history of "micromeritics," a term used by early researchers to describe the science of small particles, and the related invention of laboratory instruments for characterizing very fine particles. The historical view provides insights into the role that Progressive Era government agencies played in advancing esoteric science and applying this knowledge to the regulation of workplace air pollution. Micromeritics instrumentation developed in conjunction with federal research now has many commercial applications worldwide, with characterizing airborne pollutants only a minor one. However, the continuing advances in the micromeritics field provide important laboratory measurement capabilities to environmental research organizations, such as the National Institute for Occupational Safety and Health (NIOSH).

Dose-response for retinoic acid-induced forelimb malformations and cleft palate: a comparison of computerized image analysis and visual inspection.

BACKGROUND: The objectives of this study were to (1) compare two techniques (computerized image analysis and visual morphological evaluation) for the assessment of fetal forelimb malformations and (2) increase the robustness of the dose-response curve for forelimb and cleft palate malformations resulting from all-trans retinoic acid (RA) exposure in GD 11 mice. METHODS: Pregnant CD-1 mice were administered a single oral dose of all-trans RA (0, 2.5, 10, 30, 60, or 100 mg/kg) on GD 11. GD 18 fetuses were examined for malformations using visual morphological scoring and computerized image analysis. RESULTS: Dose-dependent changes occurred in the size and shape of the humerus, radius, and ulna based on both assessment methodologies. The most sensitive indicators for the lowest effect level (10 mg/kg) on forelimbs were roundness, a shape measurement determined by image analysis, and visual morphological scoring. For all other bone measurements (proximal and distal width, area, length, and perimeter), the lowest effect level was 30 mg/kg. The maximum effect for limb defects and total malformed fetuses was seen at 60 mg/kg and higher. Incidence of cleft palate increased over the entire range of administered doses reaching a maximum of 74% (100 mg/kg). CONCLUSIONS: Overall, results indicate that computerized image analysis was no more sensitive in detecting changes in the humerus, radius, and ulna than gross visual examination. Dose-response modeling of developmental endpoints yielded comparable benchmark dose levels for long bones and cleft palate that ranged from 0.24 to 7.6 mg/kg all-trans RA. Birth Defects Res B 71:289-295, 2004.

Development of an oral cancer slope factor for Aroclor 1268.

Rodent cancer bioassays indicate that substantial differences exist among PCB mixtures in terms of tumorigenic response, although no bioassay has been conducted with Aroclor 1268. The USEPA has used data from these studies to develop three sets of PCB cancer slope factors (CSFs) ranging from 0.07 to 2.0(mg/kg-day)(-1). Selection of the appropriate CSF for risk assessment purposes is largely a function of the exposure circumstances rather than the PCB mixture involved. Since the congener composition of Aroclor 1268 differs substantially from that of the predominant PCB mixture (Aroclor 1254) used to derive the CSFs, the validity of applying existing CSFs to Aroclor 1268 is questionable. We have therefore undertaken the task of developing cancer potency estimates specifically for Aroclor 1268. Potency estimation approaches for Aroclor 1268 were based in part on existing potency estimates for other PCB mixtures, coupled with the relative 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQ) content and bioaccumulation potential of PCB mixtures. As such, both Ah-dependent and independent mechanisms of tumorigenesis were considered relevant. Both empirical evidence and mechanistic considerations indicate Aroclor 1268 is substantially less toxic and carcinogenic than the PCB mixtures that have been used by the USEPA to develop CSFs. The present analysis indicates that Aroclor 1268 is likely to be 1-2 orders of magnitude less potent than Aroclor 1254 in terms of potential tumorigenicity. Therefore, we suggest an upper-bound cancer potency factor of 0.27(mg/kg-day)(-1) for Aroclor 1268, a value that is 7- to 8-fold lower than the USEPA's current default, but nonetheless adequately conservative.

Immunological function in mice exposed to JP-8 jet fuel in utero.

Immunological parameters, host resistance, and thyroid hormones were evaluated in F1 mice exposed in utero to jet propulsion fuel-8 (JP-8). C57BL/6 pregnant dams (mated with C3H/HeJ males) were gavaged daily on gestation days 6-15 with JP-8 in a vehicle of olive oil at 0, 1000, or 2000 mg/kg. At weaning (3 weeks of age), no significant differences were observed in body, liver, spleen, or thymus weight, splenic and thymic cellularity, splenic CD4/CD8 lymphocyte subpopulations, or T-cell proliferation. Yet, lymphocytic proliferative responses to B-cell mitogens were suppressed in the 2000 mg/kg treatment group. In addition, thymic CD4-/CD8+ cells were significantly increased. By adulthood (8 weeks of age), lymphocyte proliferative responses and the alteration in thymic CD4-/CD8+ cells had returned to normal. However, splenic weight and thymic cellularity were altered, and the IgM plaque forming cell response was suppressed by 46% and 81% in the 1000 and 2000 mg/kg treatment groups, respectively. Furthermore, a 38% decrease was detected in the total T4 serum hormone level at 2000 mg/kg. In F1 adults, no significant alterations were observed in natural killer cell activity, T-cell lymphocyte proliferation, bone marrow cellularity and proliferative responses, complete blood counts, peritoneal and splenic cellularity, liver, kidney, or thymus weight, macrophage phagocytosis or nitric oxide production, splenic CD4/CD8 lymphocyte subpopulations, or total T3 serum hormone levels. Host resistance models in treated F1 adults demonstrated that immunological responses were normal after challenge with Listeria monocytogenes, but heightened susceptibility to B16F10 tumor challenge was seen at both treatment levels. This study demonstrates that prenatal exposure to JP-8 can target the developing murine fetus and result in impaired immune function and altered T4 levels in adulthood.

Evaluation of the carcinogenicity of 1,1-dichloroethylene (vinylidene chloride).

The U.S. Environmental Protection Agency has classified 1,1-dichloroethylene (vinylidene chloride; VDC) as a "C" carcinogen and has developed an inhalation unit risk value and an oral cancer slope factor for this chemical. The development and use of these cancer potency estimates for risk assessment purposes are questionable. The inhalation unit risk value is based on increased kidney adenocarcinomas in Swiss mice from one study. This type of cancer was not increased in female mice or in rats or hamsters in the same study nor in male mice of a similar strain in another study with higher VDC exposures. The VDC oral cancer slope factor is based on a non-statistically significant increase in adrenal pheochromocytomas in male rats following oral exposure in a standard National Toxicology Program chronic bioassay. Both human and animal literature relevant to VDC carcinogenicity was reviewed according to the USEPA draft Guidelines for Carcinogen Risk Assessment with the objective of determining the weight-of-evidence for VDC carcinogenicity. We conclude that information currently available for VDC is most appropriately characterized in a weight-of-evidence narrative by the descriptor "inadequate for an assessment of human carcinogenic potential." For chemicals with this descriptor, dose-response assessment is not indicated. Under this guidance, quantitative estimates of cancer risks associated with VDC exposure are inappropriate until additional, more definitive evidence for human carcinogenicity becomes available.