Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 13 (2012) / Chapter Skim
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6 Piperidine
6 Piperidine
Pages 167-201
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From page 167... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 168... ...
Airborne concentrations below the AEGL-1 represent exposure concentrations that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL.
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From page 169... ...
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.
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From page 170... ...
(BASF 1993) AEGL-2 50 ppm 50 ppm 33 ppm 13 ppm 8.3 ppm Nasal irritation (disabling)
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From page 171... ...
Experimental Studies, Case Reports, and Anecdotal Data Bazarova and Migoukina (1975) reported an irritation threshold for piperidine of 90 mg/m3 (26 ppm)
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From page 172... ...
Clinical signs, mortality, food consumption, body weights, and gross and microscopic findings were evaluated during or after exposure. Multiple clinical signs were observed at all concentrations.
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From page 173... ...
Male and female rats exposed at 1,190 ppm and 1,540 ppm and females exposed at 810 ppm lost weight during the first week of observation, gained weight during the second week, and the males weighed 13-29% less than controls and the females weighed 14-19% less than controls at the end of the observation period. A postmortem evaluation was conducted, but no data were provided.
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From page 174... ...
Rats were observed daily for clinical signs before, during, and after exposure, and body weights were measured at the beginning of the study and at 1-week intervals thereafter. Subgroups of five animals/sex/group were subjected to an extensive battery of neurofunctional tests before exposure and on days 2, 8, 14, and 28.
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From page 175... ...
The reddish crust was indicative of upper respiratory tract irritation. Each subgroup of five male rats exposed at 100 ppm weighed 3.4% (n.s.)
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From page 176... ...
for 6 h/day on gestation days 6-15. Dams were observed daily for clinical signs, weighed on gestation days 2, 3, and 6 and at 2-day intervals until gestation day 20, and had food consumption measured at intervals between weighing days.
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From page 177... ...
At 20 ppm, lack of response to a knock on the chamber door was noted on each exposure occasion, and closed or half-closed eyes and hunched posture were observed once during the study. No clinical signs were reported after daily exposure to piperidine at 20 ppm, and no clinical signs related to exposure were observed at 5 ppm.
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From page 178... ...
(1988) reported that piperidine induced DNA strand breaks in mouse lymphoma cells with rat liver S9, but not alkaline unwinding with or without S9.
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From page 179... ...
, Upper respiratory tract irritation at all concentrations; closed eyes and BASF 1990 6 h/d for 5 d salivation at 200 ppm. 5, 20, 100 ppm Upper respiratory tract irritation at 100 ppm (350 mg/m3)
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From page 180... ...
1990 (20, 70, 280 mg/m3) , gestation days 6-15 during or after first exposure, hunched posture after most exposures; at 20 ppm, ocular irritation and hunched posture observed once Fetuses: no effects.
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From page 181... ...
for 6 h/day caused nasal irritation signs of ocular irritation and salivation also were observed after each daily exposure at 200 ppm (BASF 1990, 1993; Hughes et al.
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From page 182... ...
SPECIAL CONSIDERATIONS 4.1. Metabolism, Disposition, and Kinetics Piperidine is absorbed from the respiratory tract, digestive tract, and skin (Gehring 1983)
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From page 183... ...
(1990) reported LD50 values of 445 mg/kg for male and female rats combined; clinical signs included ptosis, respiratory effects, lethargy, ataxia, tremors, salivation, and lacrimation.
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From page 184... ...
The LC50 is 3,480 ppm for a 1-h exposure to the guinea pig, 1,740 ppm for a 2-h exposure to the mouse, and 1,390 ppm for a 4-h exposure to the rat. The linear correlation for concentration vs.
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From page 185... ...
(1990) observed eye closure, increased respiration, hunched posture, piloerection, salivation, a lack of response to a knock on the chamber door after the first exposure at 80 ppm in pregnant rats exposed for 6 h/day during gestation days 6-15.
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From page 186... ...
A no-effect level for nasal irritation of 20 ppm for 6 h was selected as the end point for deriving AEGL-1 values. An uncertainty factor of 3 for interspecies differences and a factor 3 for intraspecies variability were applied.
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From page 187... ...
Severity of nasal and ocular irritation and general discomfort showed a concentration-related increase at piperidine concentrations of 50-200 ppm. Clinical signs observed at 287 ppm included ocular and nasal irritation, spasmodic respiration (probably from attempted mouth breathing because of the pungent odor)
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From page 188... ...
Clinical signs at lethal doses included effects on the eyes, upper and lower respiratory tracts, and the CNS. Dyspnea, tremors, clonic convulsions, and prostration were the most severe signs that appeared to be associated with death.
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From page 189... ...
The LC01 (448 ppm) was lower than the lowest concentration associated with death or clinical signs indicative of death (810 ppm)
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From page 190... ...
Nevertheless, the evaluation and conclusions regarding the acute inhalation toxicity of piperidine vapor and AEGL derivations could be strengthen with definitive data on the odor and irritation threshold in humans and with 1- and 8-h acute inhalation toxicity studies at concentrations in rats that would encompass lethal and nonlethal end points.
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From page 191... ...
1980. Determination of the Acute Inhalation Toxicity LC50 of Piperidine as Vapor in Sprague-Dawley Rats after a 4-Hour Exposure [in German]
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From page 192... ...
2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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From page 193... ...
Pp. 3285-3521 in Patty's Industrial Hygiene and Toxicology, Vol.
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From page 194... ...
. Uncertainty factors: 3 for interspecies differences because the effects are mediated by direct contact with nasal epithelium, which has similar cell composition among species but different cell distribution and nasal morphology; linear correlation for the concentration vs.
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From page 195... ...
. Uncertainty factors: 3 for interspecies differences because the effects are mediated by direct contact with nasal mucosa, which has similar cell composition among species but different cell distribution and nasal morphology; the data indicate only small variations in LC50 values for three different species 3 for intraspecies variability because the nasal epithelium does not vary among individuals in the population.
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From page 196... ...
of 448 ppm calculated by probit analysis. Time scaling: Cn × t = k; n = 1.5 (derived by regression analysis of LC50 data for rats, guinea pigs, and mice)
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From page 197... ...
Piperidine 197 10-min AEGL-3: C = (71,966.1488 ppm-min ÷ 10 min)
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From page 198... ...
End point/Concentration/Rationale: No-effect level for nasal irritation at 100 ppm for 6 h Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3, because the effects are mediated by direct contact with nasal epithelium, which has similar cell composition among species, although cell distribution and nasal morphology differ; the linear correlation coefficient for the concentration vs. time relationship for LC50 values for three species is -0.96 and the concentration-time relationships are similar, not varying by more than 30%, indicating the response is similar among the three species Intraspecies: 3, because the nasal epithelium does not vary among individuals in the population Modifying factor: None Animal-to-human dosimetric adjustment: None Time scaling: Cn × t = k; n = 1.5 based on regression analysis of LC50 values for the rat exposed for 4 h, the mouse exposed for 2 h, and the guinea pig exposed for 1 h.
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From page 199... ...
Severity of nasal irritation in the rat increased with increasing exposure concentration, but there was no involvement of other regions of the respiratory tract. Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3, because the effects are mediated by direct contact with nasal epithelium, which has similar cellular composition among species, although cell distribution and morphology differ; the linear correlation coefficient for the concentration vs.
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From page 200... ...
The acute inhalation study was conducted according to standard protocol and showed a reasonable concentration-response relationship for lethality and a clear concentration-response relationship for severity of clinical signs. The LC01 was a good approximation of the lethality threshold; therefore, the AEGL-3 values should be within the limits that would protect humans from lethal exposure to piperidine vapor.
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From page 201... ...
Piperidine 201 APPENDIX C CATEGORY PLOT FOR PIPERIDINE Chemical Toxicity - TSD All Data Piperidine 10000.0 Human - No Effect Human - Discomfort 1000.0 Human - Disabling Animal - No Effect ppm 100.0 Animal - Discomfort AEGL-3 Animal - Disabling 10.0 AEGL-2 Animal - Some Lethality Animal - Lethal AEGL-1 1.0 AEGL 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-1 Category plot of animal and human toxicity data in relation to AEGL values for piperidine.
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