Sensory irritation and use of the best available science in setting exposure limits: Issues raised by a scientific panel review of formaldehyde human research studies.

As a high production volume chemical with recognized sensory irritation and widespread exposure, the human health risk potential of formaldehyde has been reviewed by many international regulatory agencies and scientific advisory bodies. A scientific panel, the Human Studies Review Board, under the auspices of the EPA's Toxic Substances Control Act (TSCA) program recently reviewed the sensory irritation studies included in the 2022 Draft Integrated Risk Information System (IRIS) Formaldehyde Hazard Assessment in the context of their use in a weight of evidence evaluation of acute inhalation health effects. This panel issued a series of recommendations on the use of these studies for the purposes of calculating exposure limits (e.g., study design preferences; uncertainty adjustment). Considering that these recommendations might reflect topic areas with varying degrees of scientific consensus, this commentary reflects on commonalities and distinctions amongst international formaldehyde exposure limits based on sensory irritation. Notably, each review panel charged with an assessment of the science recommended that no adjustment was needed to account for either exposure duration or human variability. These areas of scientific consensus should be considered as the best available science for the purposes of setting exposure limits in the anticipated TSCA Risk Evaluation on formaldehyde.

Chamber for testing asbestos-containing products: validation and testing of a re-created chrysotile-containing joint compound.

Joint compound products containing chrysotile asbestos were commonly used for building construction from the late 1940s through the mid-1970s. Few relevant data exist to support reconstructing historical worker exposures to fibers generated by working with this material. Therefore, we re-created 1960s-era chrysotile-containing joint compound (JCC) and compared its characteristics to a current-day asbestos-free joint compound (JCN). Validation studies showed that a bench-scale chamber with controlled flow dynamics, designed to quantify particulate emissions from joint compound products, provided precise and reliable measurements of generated airborne dust mass, chrysotile fiber concentrations, and corresponding activity-specific emission rates. Subsequent chamber studies characterized fibers counted by phase contrast microscopy (PCM) per mass of respirable dusts and total suspended particulate dusts (total dusts), generated during JCC sanding or sweeping, as well as corresponding dust emission rates for JCC and JCN, and the ratio of total to respirable dust mass for JCN. From these data we estimated factors, F(CH-rd) and F(CH-td) (in units of f cm(-3) per mg m(-3)), by which respirable JCN dust mass concentrations collected during construction use can be converted to corresponding airborne PCM fiber concentrations generated by sanding or sweeping JCC. For sanding, median values (95% confidence limits) of F(CH-rd) and F(CH-td) were estimated to be 0.044 (0.039-0.050) and 0.212 (0.115-0.390) f cm(-3) per mg m(-3), respectively. The F(CH-td) to F(CH-rd) ratio indicates that approximately five times as many airborne PCM fibers are anticipated per unit air volume sampled when JCC dust is collected on cassettes (as done historically), than when respirable JCC dust is collected on cyclones. As the sizes of individual fibers collected appear to be primarily respirable, this difference may be a sampling artifact and suggests caution in interpreting historical fiber concentration measures made using cassettes during work with JCC-like materials. F(CH-rd) can be used with published and newly generated field measurements of respirable dust mass concentrations associated with the use of JCN or equivalent JCN materials to better characterize historical worker exposures to PCM fibers from use of JCC or equivalent JCCs. The experimental process described also can be used to develop conversion factors for other combinations of modern-day asbestos-free and historical chrysotile-containing products.

Gene expression fingerprints of largemouth bass (Micropterus salmoides) exposed to pulp and paper mill effluents.

Effluents from pulp and paper mills that historically have used elemental chlorine in the bleaching process have been implicated in inhibiting reproduction in fish. Compounds with estrogenic and androgenic binding affinities have been found in these effluents, suggesting that the impairment of reproduction is through an endocrine-related mode of action. To date, a great deal of attention has been paid to phytoestrogens and resin acids that are present in mill process streams as a result of pulping trees. Estrogen and estrogen mimics interact directly with the estrogen receptor and have near immediate effects on gene transcription by turning on the expression of a unique set of genes. Using differential display (DD) RT-PCR, we examined changes in gene expression induced by exposure to paper mill effluents. Largemouth bass were exposed to 0, 10, 20, 40, and 80% paper mill effluent concentrations in large flow-through tanks for varied periods of time including 7, 28 or 56 days. Plasma hormone levels in males and females and plasma vitellogenin (Vtg) in females decreased with dose and time. Measurements of changes in gene expression using DD RT-PCR suggest that the gene expression patterns of male fish do not change much with exposure, except for the induction of a few genes including CYP 1A, a protein that is induced through the action of the Ah receptor in response to dioxin and similar polyaromatic hydrocarbons. However, in the case of females, exposure to these effluents resulted in an up-regulation of CYP 1A that was accompanied by a generalized down-regulation of genes normally expressed during the reproductive season. These antiestrogenic changes are in agreement with previous studies in bass exposed to these effluents, and could result in decreased reproductive success in affected populations.

Effects of pulp and paper mill effluents on reproductive success of largemouth bass.

This study evaluated the effects of bleached and unbleached kraft mill effluent on reproductive success of largemouth bass (Micropterus salmoides). Bass were exposed to effluent concentrations (0, 10, 20, 40, or 80%) for 28 and 56 d. Parameters measured included hepatosomatic index (HSI) and gonadosomatic index (GSI) and plasma concentrations of 17beta-estradiol (E2), 11-ketotestosterone (11-KT), and vitellogenin (VTG). At the end of the 56-d period, bass were moved to hatchery ponds to evaluate spawning success. Spawning mats with eggs either were brought indoors for evaluation of fecundities, hatchabilities, and egg and fry size (measured at age 3 d), or were left in ponds and fry number and size recorded (average age of 14 d). Effluent exposure was verified by measuring resin acids (isopimaric, abietic. and dehydroabietic acids) in bile. Compared to controls, exposed bass had greater concentrations of resin acids in bile. In general, exposed females had lower concentrations of E2 and VTG (> or = 20% effluent), whereas males had lower concentrations of 11-KT (> or = 20% effluent) and increased E2 (> or = 20% effluent). The HSI values increased in females (> or = 10% effluent), and GSI values decreased in both sexes (> or = 40% effluent). Fecundity, egg size, and hatchability did not differ across treatments, but an increase in the frequency of fry abnormalities and a decrease in fry weights was observed at effluent exposures of 40% and higher. However, results from the pond study, revealed a significant reduction in fry growth and survival (> or = 10%). This decline may have been caused by an increased frequency of deformities, in conjunction with alterations of growth. These changes could have resulted from alterations in egg quality because of failure of parental reproductive systems, from acute embryo toxicity after translocation of contaminants from the mother to the developing embryo, or from both.