title: Comparative pulmonary toxicity of inhaled metalworking fluids in rats and mice.
abstract: Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m3for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.
authors.affiliation: 1 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Ryan
authors.affiliation: 1 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cesta
authors.affiliation: 1 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbert
authors.affiliation: 2 Experimental Pathology Labs Inc., Morrisville, NC, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Brix
authors.affiliation: 1 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cora
authors.affiliation: 1 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Witt
authors.affiliation: 3 Biostatistics Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Kissling
authors.affiliation: 1 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
mesh_terms: D000818:Animals; D005260:Female; D019570:Inhalation Exposure / Q000032:analysis*; D007830:Larynx / Q000737:chemistry / Q000187:drug effects; D054327:Lubricants / Q000633:toxicity*; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008669:Metallurgy; D051379:Mice; D009666:Nose / Q000737:chemistry / Q000187:drug effects; D009821:Oils / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D013501:Surface-Active Agents / Q000633:toxicity; D018675:Toxicity Tests
chemical_list: D054327:Lubricants; D009821:Oils; D013501:Surface-Active Agents
keywords: Metalworking fluids; in vivo; inhalation exposure; pulmonary fibrosis; respiratory toxicity