Impact of Coexposure to Ozone on the Carcinogenic Potential of Inhaled Chromium. I. Effects on Retention and on Extra- and Intracellular Distribution

Abstract

A health hazard to welders is development of lung cancer. It is believed that this is likely due, in part, to the presence in welding fumes of several hexavalent chromium (Cr[VI]) species, whose solubility depends primarily on which process (i.e., manual metal arc verus metal-inert gas) is used. However, inhalation of Cr alone is uncommon in this setting. Thus, an examination of potential contributions from other coinhalants in creating or enhancing conditions whereby inhaled fume-associated Cr (primarily the insoluble forms) may initiate cancer is critical to increasing our understanding and preventing this particular occupational disease. One major chemical species formed and released during welding is ozone (O3). Though implications of adverse pulmonary effects from individual exposure to Cr or O3 have been investigated, those from simultaneous exposure are unclear. To begin to address whether the carcinogenic potential of insoluble Cr[VI] agents might be enhanced in hosts inhaling mixtures of Cr and O3 versus Cr alone, analyses of total lung Cr burden, Cr retention in lung epithelium and interstitium, and potential shifts in lung cell distribution of Cr from the cytoplasm to nuclei were undertaken in F-344 rats exposed nose-only (5 h/d, 5 d/wk for up to 48 wk) to an extrapolated occupationally relevant level of Cr (360 micrograms Cr/m3 as calcium chromate) alone and in combination with 0.3 ppm O3. Overall, there was only a nominal effect from O3 on Cr retention or on distribution of Cr particles among extracellular sites and within lung cells. However, there were O3-related effects upon mechanisms for clearing the Cr from the deep lung, specifically at the levels of particle uptake and postphagocytic/endocytic processing by macrophages. This O3 exposure-related shift in normal pulmonary clearance might potentially increase the health risk in workers exposed to other insoluble or poorly soluble carcinogenic Cr compounds.

Cadmium Associated With Inhaled Cadmium Oxide Nanoparticles Impacts Fetal and Neonatal Development and Growth

“…Determination of Cd tissue content. Preweighed maternal samples of lung, liver, kidney, blood, uterus, placentas, as well as 17.5 dpc fetuses, and whole neonates were assessed for total Cd using a previously described procedure (Cohen et al, 2003). Briefly, tissues were placed into Teflon beakers with ultrapure nitric acid (Optima grade; Fisher Scientific) and heated to 100°C -110°C and allowed to cool overnight.…”

Effect of Inhaled Chromium on Pulmonary A1at

“…To analyze A1AT from Cr 6+ -exposed hosts, male F344 rats (Charles River, Raleigh, NC) were exposed (10 rats/exposure group/duration) nose-only, 5 h/day, 5 days/wk for 4, 8, 12, 24, or 48 wk to filtered air or to 360-µg Cr/m 3 aerosols generated by nebulizing aqueous calcium chromate suspensions (pH 7) as previously described (Cohen et al, 2002). Hourly samples were collected on dedicated port filters to monitor Cr levels.…”

“…In this study, rather than initiating de novo exposures, BALF from rats that had been repeatedly exposed to occupationally encountered Cr 6+ agents for periods up to 48 wk (Cohen et al, 1997(Cohen et al, , 1998(Cohen et al, , 2002 were analyzed for A1AT antielastase activity. The justification for this approach was twofold: (1) Cr 3+ formed in the pulmonary extracellular spaces as detoxification products of inhaled Cr 6+ would then be able to interact with the extracellular A1AT, and (2) use of BALF from hosts exposed for increasing total periods would permit a preliminary determination to be made as to whether some threshold level of Cr in the lungs needed to be attained for an effect to be observed.…”

Pulmonary Immunotoxic Potentials of Metals Are Governed by Select Physicochemical Properties: Chromium Agents

“…Using previously described procedures (Cohen et al, 1996(Cohen et al, , 1997a(Cohen et al, , 2003, atmospheres of each soluble agent were generated by nebulizing a dilute solution (pH 7.2-7.4) via a Collison nebulizer (BGI, Waltham, MA). Atmospheres of insoluble particles were similarly generated, except that insoluble CaCrO 4 was purchased in the appropriate size.…”

“…Our NIEHS Center Analytical Core procedures used in earlier experiments (Cohen et al, 1997a(Cohen et al, , 2003 were applied to determine the amount of Cr (for each agent) in homogenized lung samples isolated at each timepoint (as well as on Day 0 in uninfected lungs). Each final isolate (in 0.5 ml 2% nitric acid) was analyzed for Cr using a Solaar Model M6 AA spectrophotometer (with Zeeman background correction) with GF95 graphite furnace.…”