Prediction of an occupational exposure limit for a mixture on the basis of its components: application to metalworking fluids.

Using a previously developed mouse bioassay, a semisynthetic metalworking fluid (MWF "B") and its major components were evaluated. In mice MWF "B" and its components produced both sensory (S) and pulmonary (P) irritation. Using respiratory frequency (f) depression, concentration-response relationships were developed for each component as well as for MWF "B." From such relationships the concentration capable of evoking a 50% decrease in mean f was determined for each component and designated as RD50S if the decrease in f was due to sensory irritation, or RD50P if the decrease in f was due to pulmonary irritation. Based on RD50P values, the results indicated that the alkanolamides, potassium soap, sodium sulfonate, and triazine components were similar in irritation potency both to one another and to MWF "B." Through an examination of potency and fractional composition it was concluded that these five components largely contributed to the irritancy of MWF "B." From the RD50P values, occupational exposure limits that would protect workers from respiratory irritation were proposed for MWF "B" and each of its components. Using the approach of the American Conference of Governmental Industrial Hygienists for mixtures, an occupational exposure limit was calculated for MWF "B" employing the component data. The two limits for MWF "B" were similar to one another, suggesting that exposure limits for MWFs may be obtained through the evaluation of the fluids themselves or through evaluation of the components.

Respiratory effects of a synthetic metalworking fluid and its components.

A synthetic metalworking fluid, MWF "A", and its major components were evaluated using a previously developed mouse bioassay. This fluid and its components evoked sensory (S) and pulmonary (P) irritation in mice. For MWF "A" and each of its components, a concentration-response relationship was developed on the basis of respiratory frequency (fR) responses. From such relationships, the concentration capable of evoking a 50% decrease in mean fR was determined for MWF "A" and each component (RD50). RD50S or RD50P was used to distinguish decreases in fR that were due to sensory irritation (S) from those due to pulmonary irritation (P). From RD50P values, it was concluded that the fatty acid alkanolamide condensates, tolutriazole, and triazine-type biocide components were similar in potency to one another and similar in potency to MWF "A". By examining potency and fractional composition, it was concluded that the fatty acid alkanolamide condensates and the triazine-type biocide largely contributed to the irritancy of MWF "A". From RD50P values, occupational exposure limits were proposed for MWF "A" and each of its components. The current Threshold Limit Value of 10 mg/m3 established by the American Conference of Governmental Industrial Hygienists for "particulates not otherwise classified" (PNOC) would be inadequate to protect workers from the irritating properties of MWF "A" and most of its components.

Evaluation of airborne particulates and fungi during hospital renovation.

This study was conducted over 30 weeks on a hospital floor undergoing partial renovation. Some patients housed on the floor were immunosuppressed, including bone marrow transplant recipients. The construction zone was placed under negative pressure and was separated from patient rooms by existing hospital walls and via erection of a temporary barrier. Other control measures minimized patient exposure to airborne materials. Air sampling was done for 3 weeks prior to construction, 24 weeks during construction, and 3 weeks after renovation was completed. Airborne particulate concentrations, total spore counts, particle size, and fungal species were assessed. At the beginning of the renovation there were increases in airborne particulates (from 0.2 to 2.0 mg/m3) and fungal spores (from 3.5 to 350 colony forming units (CFU/m3), but only in the construction zone. Throughout the remainder of the renovation, particulate and fungal spore levels fluctuated inside the construction zone but remained close to baseline values in the patient area. When renovation was completed, particulates and spore counts inside the construction zone decreased to preconstruction levels. The primary fungus isolated from air samples was Penicillium. This study demonstrated that control measures were effective in reducing exposures of hospitalized patients to airborne particulates and spores and in reducing the increased risk of aspergillosis and other fungal infections associated with hospital construction projects. The data from this study may be useful in establishing exposure guidelines for other health care settings.

An approach for evaluating the respiratory irritation of mixtures: application to metalworking fluids.

Recently, the sensory and pulmonary irritating properties of ten metalworking fluids (MWF) were assessed using a mouse bioassay. Relative potency of the MWFs was estimated, but it was not possible to identify the component(s) responsible for the the respiratory irritation induced by each MWF. One of the ten fluids, MWF "ET", produced sensory and pulmonary irritation in mice, and it was of moderate potency in comparison to the other nine MWFs. MWF "E" had three major components: tall oil fatty acids (TOFA), sodium sulfonate (SA), and paraffinic oil (PO). In the present study, the sensory and pulmonary irritating properties of these individual components of MWF "E" were evaluated. Mixtures of the three components were also prepared and similarly evaluated. This analysis revealed that the sensory irritation from MWF "E" was largely due to TOFA, whereas SA produced the pulmonary irritation observed with MWF "E". Both TOFA and SA were more potent irritants than was MWF "E", and the potency of TOFA and/or SA was diminished through combination with PO. There was no evidence of synergism of the components when combined to form MWF "E". This approach for identifying the biologically "active" component(s) in a mixture should be useful for other MWFs. Furthermore, the approach should be easily adapted for other applications involving concerns with mixtures.

Respiratory responses of mice exposed to thermal decomposition products from polymers heated at and above workplace processing temperatures.

Mice were exposed to thermal decomposition products (TDP) released from acrylonitrile butadiene styrene (ABS), polypropylene-polyethylene copolymer (CP), polypropylene homopolymer (HP), or plasticized polyvinylchloride (PVC). These resins were heated in a temperature programmable furnace, at and above workplace processing temperatures. LC50 and RD50 values were obtained on the basis of resin mass loaded in the furnace. LT50 values were determined at the respective LC50 masses. RD50 values were also obtained on the basis of particulate concentrations measured during heating of each resin. The results of this study indicated that PVC and HP were more toxic and faster-acting than wood, while ABS and CP were much more toxic and much faster-acting than wood. At processing temperatures between 200-300 degrees C, RD50 values (based on particulate concentrations) were 21.1, 3.51, 2.60, and 11.51 mg/m3 for ABS, CP, HP, and PVC. Exposure limits of 0.63, 0.11, 0.08, and 0.35 mg/m3 were recommended for TDP of ABS, CP, HP, and PVC to protect workers from their irritating properties. Because there are few, if any, guidelines for recognition, evaluation, or control of TDP, the experimental approach and results of this study should be useful to health and safety professionals.

Computer programs for calculation of median effective dose (LD50 or ED50) using the method of moving average interpolation.

Over the past 40 years, toxicologists and pharmacologists have used tables published by Weil for the determination of LD50 (or ED50) values and their associated 95% confidence intervals. With the advances in computer technology, it is now common for investigators to have personal computers in their laboratories. Therefore, two identical programs were developed for determination of the LD50 (or ED50) which may be run on a personal computer. One of these programs was written in BASIC, and the other in FORTRAN. The programs are easy and rapid to use, requiring minimum computer hardware and little, if any, knowledge of programming. They also offer more user flexibility than the previously published tables of Weil, in that there are fewer restrictions on the number of animals and number of dosage levels used in an experiment. The output of the programs may be typed on the screen of a computer monitor, and may be sent to a printer. The two programs calculate the LD50 and 95% confidence intervals for the LD50. These programs should be valuable for many investigators.