Risk assessment of exposure to chemicals having a toxic endpoint routinely uses the reference dose (RfD) approach based on uncertainty factors of 10. The purpose of this investigation was to evaluate whether the magnitude of the U.S. Environmental Protection Agency (EPA) 10× uncertainty factors has scientific merit when compared with data from recent human and animal experimental studies. A compilation and comparison of ratios between LOAEL/NOAEL (lowest observed adverse effect level/no observed adverse effect level) and subchronic/chronic values was made for six chlorinated compounds, namely, carbon tetrachloride, methylene chloride, pentachlorophenol, monochlorobenzene, chlorpyrifos, and 1,1‐dichloroethane. Data sets demonstrated that 91.3% of the LOAEL/NOAEL ratios were ≤6 while 87% of the ratios for the same parameter were ≤5. Furthermore, subchronic/chronic ratios were ≤3.5. From our investigation we concluded that automatic safety factors of 10× are not scientifically supportable and are overly conservative for the chlorinated compounds studied here.