Derivation of Occupational Thresholds of Toxicological Concern for Systemically Acting Noncarcinogenic Organic Chemicals

Many substances in workplace do not have occupational exposure limits. The threshold of toxicological concern (TTC) principle is part of the hierarchy of approaches useful in occupational health risk assessment. The aim of this study was to derive occupational TTCs (OTTCs) reflecting the airborne concentrations below which no significant risk to workers would be anticipated. A reference dataset consisting of the 8-h threshold limit values-Time-Weighted Average for 280 organic substances was compiled. Each substance was classified into low (class I), intermediate (class II), or high (class III) hazard categories as per Cramer rules. For each chemical, n-octanol:water partition coefficient and vapor pressure along with the molecular weight were used to predict the blood:air partition coefficient. The blood:air partition coefficient along with data on water solubility and ventilation rate allowed the prediction of pulmonary retention factor and absorbed dose in workers. For each Cramer class, the distribution of the predicted doses was analyzed to identify the various percentile values corresponding to the OTTC. Accordingly, for Cramer classes I-III, the OTTCs derived in this study correspond to 0.15, 0.0085, and 0.006 mmol/d, respectively, at the 10th percentile level, while these values were 1.5, 0.09 and 0.03 mmol/d at the 25th percentile level. The proposed OTTCs are not meant to replace the traditional occupational exposure limits, but can be used in data-poor situations along with exposure estimates to support screening level risk assessment and prioritization.