however, death occurred only at concentrations that caused dyspnea, CNS toxicity, and prostration. Therefore, the severity of effects from piperidine shows a clear continuum ranging from nasal irritation to death. Piperidine has no demonstrated carcinogenic activity, it is not genotoxic in Salmonella typhimurium, and it is not toxic to the developing rat fetus at the concentrations tested.
The database on piperidine in humans is very small. Inhalation exposure to piperidine may cause sore throat, coughing, labored breathing, and dizziness. The odor threshold is reported to be <2 ppm, and 2-5 ppm is reported to be tolerated by unacclimated individuals for only a brief time because of its pungent odor. The irritation threshold for humans was reported to be 26 ppm. At an odor threshold of 0.37 ppm, a level of distinct odor awareness would be 5.9 ppm (van Doorn et al. 2002).
AEGL-1 values were based on the no-effect level (20 ppm for 6 h) for nasal irritation in rats. Uncertainty factors of 3 for interspecies differences and 3 for intraspecies variability were applied. The rationale for selecting those factors included the following: (1) the effect observed at 50 ppm was mediated by direct contact of piperidine with the nasal epithelium without involvement of other regions of the respiratory tract; and (2) the cell composition of the nasal mucosa is similar between species and among individuals within the population, although the cell distribution and nasal morphology differ among species. In addition, the relationship between concentration vs. time for LC50 (lethal concentration, 50% lethality) values was similar in mice, guinea pigs, and rats; they did not vary by more than 30%. The linear correlation coefficient was -0.96. After applying a total uncertainty factor of 10, the resulting value of 5 ppm was time scaled based on the equation, Cn × t = k, where n = 1.5. The value of n was derived from a regression analysis of the LC50 values for the mouse, guinea pig, and rat.
AEGL-2 values were based on exposure of rats to piperidine at 200 ppm for 6 h, which caused nasal irritation without salivation or evidence of ocular irritation. The rationale for selecting uncertainty factors and the time-scaling procedure were the same as those described for the AEGL-1 values.
AEGL-3 values were based on the LC01 (lethal concentration, 1% lethality) calculated from a 4-h acute inhalation study in rats. The LC01 of 448 ppm is less than the lowest concentration that caused one death among 20 rats (5% lethality) and greater than the highest concentration that caused no deaths or clinical moribund signs. Therefore, the LC01 appeared to be a good estimate of the threshold for lethality. Uncertainty factors of 3 for interspecies differences and 3 for intraspecies variability were applied to the LC01. The rationale for selecting the uncertainty factors was the same as described for AEGL-1 values. In addition, larger factors for interspecies differences or intraspecies variability would have produced values for the 4-h and 8-h durations that were lower than the irritation threshold of 26 ppm. The time-scaling procedure was the same as described for AEGL-1 values.
AEGL values for piperidine are presented in Table 6-1.