Physicochemical Properties of Nonreactive Volatile Organic Chemicals to Estimate RD50: Alternatives to Animal Studies

Nasal pungency and odor of homologous aldehydes and carboxylic acids

“…There are various differences between the RD 50 technique and our methodology, besides the obvious species difference, but perhaps exposure time and exposed body surface are the two most relevant for sensory irritation potency. A solvation equation has also been used to describe upper respiratory tract irritation in mice (Alarie et al 1995). The same major factors apply to both the log 1/NPT and log 1/RD 50 equations, but the coefficients of pi, alpha, and beta are appreciably larger for the nasal pungency equation.…”

An assessment of air quality reflecting the chemosensory irritation impact of mixtures of volatile organic compounds

“…(3) are not only the rapid (seconds) eye irritation and nasal pungency thresholds in humans, but the longer term (minutes) mouse assay (Alarie 1966;Alarie 1973;Nielsen et al 2007;Alarie et al, 1995Alarie et al, , 1996Alarie et al, , 1998aAlarie et al, , 1998b and very long term (minutes/hours) anesthetic effects (Abraham et al 2008). VOCs have been divided into those that act by a 'physical' and those that act by a 'chemical' mechanism (Abraham et al, 2010a;Alarie et al 1995Alarie et al , 1996Alarie et al , 1998 noting that in the mouse assay test, it was possible to account for the RD 50 end point only for VOCs that acted by a 'physical' mechanism. A rather different terminology has been used in classifying the effect of VOCs on odor detection thresholds, ODTs (Abraham et al 2007).…”

“…(4) for VOCs that act through specific effects VOCs that act through physical effects, and so we then added VOCs that act specifically and for which ODT values were available (Devos et al, 1990;Nagata, 2003;Cometto-Muñiz and Cain, 1990, 1994Cometto-Muñiz et al, 1998aCometto-Muñiz and Abraham, 2008a, 2008c, 2009a, 2009b, 2010bHellman and Small, 1974;Rodriguez et al, 2011;Czerny et al, 2011). We also included VOCs that act specifically, and had been studied in the mouse assay (Alarie et al, 1995(Alarie et al, , 1996(Alarie et al, , 1998Schaper 1993). Other sets of data we used include those for inhalation anesthesia (Abraham et al, 2008), gaseous convulsant activity (Abraham and Acree, 2009), the Draize rabbit eye test and tadpole narcosis corrected to the gaseous state (Bowen et al, 2006).…”

“…We intend to pursue this in the future. Devos et al, 1990 3.868 Mouse test, Alarie et al, 1995Alarie et al, , 1996Alarie et al, , 1998Schaper, 1993 0.469 Inhalation anesthesia, Abraham et al, 2008 6.730 Tadpole narcosis, Bowen et al, 2006 8.616 Inhalation convulsions, Abraham and Acree, 2009 7.040 Draize eye test, Abraham et al, 2003 0.526 Inhalation anesthesia, Davies et al, 1974Davies et al, , 1976 4.746 a Cometto-Muñiz and Cain, 1990Cain, , 1991Cain, , 1993Cain, , 1994Cometto-Muñiz et al, 1998a Cometto-Muñiz and Abraham, 2008aAbraham, , 2008cAbraham, , 2009aAbraham, , 2009bAbraham, , 2010aAbraham, , 2010b The probability that a given air sample containing a number of VOCs could elicit sensory irritation, denoted as Qmix, can then be calculated from the response addition expression, Eq. (6), where the letters a, b. c. … represent different VOCs.…”

Prediction of Toxicity, Sensory Responses and Biological Responses with the Abraham Model

“…The Schaper data base was used to test if log (1/RD 50 ) values for nonreactive VOCs could be correlated with gas to solvent partition coefficients, as log K, and reasonable correlations were found for a number of solvents (Abraham et al, 1994;Alarie et al, 1995Alarie et al, , 1996. In order to analyze values for a wide range of VOCs it was thought important to distinguish compounds that illicit an effect through a 'chemical' mechanism or through a 'physical' mechanism, these terms being equivalent to 'reactive' or 'nonreactive' (Alarie et al, 1998a).…”