Sunday, May 29, 2005

Inhalation Study Suggests an Exposure Limit of 0.1 mg/M3 for Soluble Oil MWF Uncontaminated by Endotoxin

A sub-acute inhalation study of effects of MWF in the laboratory was published by colleagues in Korea. BrooklynDodger takes the challenge of extrapolating risk from brief exposures to small numbers of rats to that for thousands of people exposed for years. According to the investigators:

Rats were exposed a 10 mg/m(3) concentration of metalworking fluid (MWF) [without added endotoxin] and contaminated with endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m(3) (high dose) 6 hr per day for 8 weeks [not clear how many rats per group; this effects statistical significance, imporant for the control group]. ...Lung weight increased significantly in the rats exposed to the MWF both with and without endotoxins. ... The NOx production activity of the BAL cells increased significantly in the rats exposed to the MWF with and without endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with endotoxins rather than in those exposed to MWF without endotoxins. [but still increased in the MWF only exposed rats.] In spleen cell cultures, T-cell proliferation activity was decreased... after repeated exposure to MWF with and without endotoxins....

The investigators described the fluid as: Loca emulsion oil (Shell, Korea) was selected as the watersolubleMWF because it includes few additives and is popularly used in Korea. Mineral oil constituted 80.0%–90.0% ofthe MWF (Cas. No. 64742-55-8) and 2-octyl-3-isothiazolone was less than 1% (Cas. No. 26530-20-1). No nitrosamines, formaldehyde, or ethanolamines [were detected.]

Debates about MWF health effects include the role of microbial products in respiratory effects. Endotoxin, derived from the corpses of gram negative bacteria which routinely grow in MWF, clearly contributes to effects seen in laboratory studies; it's not surprising that endotoxin by itself damages lungs. This study demonstrates that fluid without added endotoxin, apparently made up directly from concentrate, also damages lungs under these exposure circumstances. The investigators neglected to identify the emulsifier [likely a petroleum sulfonate] surely present in the formulation, and any non-ionic surfactant which might have been included. The aerosol was apparently a 5% dilution of concentrate; for mass measurements, the water part of the aerosol goes away, but the animal's respiratory systems saw droplets with typical workplace concentrations.

BrooklynDodger concludes that 10 mg/M3 is a sub-chronic effect level for a bland soluble oil uncontaminated with endotoxin, causing increased lung weight and a variety of indicators of inflammation. BrooklynDodger would appy extrapolation factors for AEL to NOAEL, for NOAEL [10% effect] to an acceptable risk rate, and for sub-chronic to chronic to identify a reference dose. For IRIS purposes, EPA's default would be 10 fold for each. Using a much less risk adverse factor of 5 for each, BrooklynDodger derives a reference dose of 0.1 mg/M3 for mild soluble oil uncontaminated with endotoxin.

Environ Toxicol. 2005 Apr;20(2):212-8.

Inflammatory and immunological responses to subchronic exposure to endotoxin-contaminated metalworking fluid aerosols in F344 rats.

Lim CH, Yu IJ, Kim HY, Lee SB, Kang MG, Marshak DR, Moon CK.Center for Occupational Toxicology, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, Daejeon, South Korea.

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