Time Course of Pulmonary Responses to Inhalation of Cotton Dust in the Guinea Pig Animal Model

Exposure to cotton (Gossypium hirsutum L.) dust can result in acute pulmonary inflammation marked by elevation of neutrophils in nasal and bronchoalveolar lavage fluids and activation of alveolar macrophages. Such exposure may also result in chest tightness and airway constriction. For this reason, OSHA has established a PEL of 0.2 mg/m for yarn manufacturing and cotton washing. This PEL is for an 8 h workday. Questions concerning an appropriate standard for extended workdays (longer than 8 h) have been raised. As an initial attempt to address this issue, we employed a guinea pig (Cavia porcellus) model exposed to 1.5 mg/m of cotton dust for 4 to 16 h and monitored pulmonary inflammation 0 and 18 h post-exposure. Total bronchoalveolar lavage cells, leukocytes, and red blood cells increased Health Effects Laboratory Div., Natl. Inst. for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505. Received 18 Aug. 1997. *Corresponding author (vic1@cdc.gov). Abbreviations: OSHA, Occupational Safety and Health Administration; NIOSH, National Institute for Occupational Safety and Health; REL, recommended exposure limit; PEL, permissible exposure limit; AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care International; FEV1, forced expiratory volume in 1 second; SE, standard error of the mean; AM, alveolar macrophages; HEPES, N-2-hydroxyethylpiperazine-N-2-ethane sulfonic acid; TNF, tumor necrosis factor. 11 CASTRANOVA ET AL.: GUINEA PIG RESPONSE TO COTTON DUST INHALATION linearly with total exposure (concentration x exposure time) both immediately and 18 h post-exposure. Macrophage activity, measured as zymosanstimulated chemiluminescence, exhibited a similar linear relationship to total exposure. These animal results suggest that the concentration-time product may be an appropriate exposure metric when evaluating the risk of acute inflammation in response to cotton dust. The byssinotic syndrome in cotton mill workers was first characterized by Schilling et al. (1955) as chest tightness, which is most pronounced on the first day of the workweek (Monday accentuation). In addition to the classic symptom of chest tightness, inhalation of cotton dust results in several other pulmonary responses (Rylander et al., 1987). Cotton mill workers may experience increased airway resistance that results in a crossshift decline in forced expiratory volume in 1 s (FEV1) (McKerrow et al., 1958). As with chest tightness, this cross-shift decline in FEV1 exhibits Monday accentuation (Merchant et al., 1972). Cotton dust exposure is also associated with an inflammatory response characterized by elevations of neutrophils in the blood (Bouhuys et al., 1961), nasal fluids (Merchant et al., 1975), and bronchoalveolar lavage fluid (Baur et al., 1993). National Institute for Occupational Safety and Health (NIOSH) has published a recommended exposure limit (REL) of <0.2 mg/m for lint-free cotton dust (NIOSH, 1994). OSHA’s current PEL is 0.2 mg/m for yarn manufacturing and cotton washing; 0.5 mg/m for textile mill house operations or for yarn manufacturing with washed cotton; 0.75 mg/m for textile slashing and weaving; and 1 mg/m for cotton waste processing and garnetting. All these PEL’s are for an 8 h workday (OSHA, 1984). Recently, the issue of longer than 8 h workdays has been raised in regard to the cotton dust PEL. For example, an 8 h exposure to 0.2 mg/m of cotton dust would result in a total daily exposure of 1.6 mg h/m, that is, the concentration-time product. If a worker were exposed at 0.18 mg/m for 10 h (1.8 mg h/m daily exposure), would the individual be at risk of acute respiratory inflammation? To date, no information is available to address this issue. The simplest approach would be that pulmonary reactions are directly related to the timeconcentration product. However, it is known that pulmonary responses to cotton dust are not as great on subsequent exposure days as they are after the initial exposure (Monday accentuation). This indicates that negative feedback mechanisms are in place to limit the reaction to cotton dust. The question is: would these limiting factors occur within an extended workday? If so, the exposureresponse relationship would deviate from linearity and a 10 h exposure to 0.18 mg/m might not be more inflammatory than an 8 h exposure to 0.2 mg/m. Extensive effort from several laboratories has resulted in the development of a guinea pig animal model for cotton dust exposure (Castranova et al., 1996). This model exhibits concentration-dependent increases in breathing rate (Ellakkani et al., 1985), airway constriction (Smith et al., 1993), neutrophil infiltration (Robinson et al., 1988), and alveolar macrophage activation (Robinson et al., 1988). As in workers, these responses exhibit Monday accentuation (Castranova et al., 1990) and a dependence on the endotoxin content of the cotton dust (Castellan et al., 1987; Robinson et al., 1995). The objective of the present investigation was to employ this animal model to investigate whether a linear relationship exists between the concentrationtime product for cotton dust inhalation and pulmonary response in guinea pigs. This was accomplished by exposing guinea pigs to an average of 1.5 mg/m cotton dust for 4 to 16 h and monitoring pulmonary reactions immediately, as well as 18 h post-exposure. MATERIAL AND METHODS