Sensory irritation mechanisms investigated from model compounds: trifluoroethanol, hexafluoroisopropanol and methyl hexafluoroisopropyl ether

Nielsen, Gunnar Damgård; Abraham, Michael H.; Hansen, Lea Frimann; Hammer, Maria; Cooksey, Christopher J.; Andonian‐Haftvan, Jenik; Alarie, Yves

doi:10.1007/s002040050281

Cited by 19 publications

(18 citation statements)

References 24 publications

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“…Esters can spontaneously participate in acyl-group transfer reactions (Nielsen 1991) or they can be hydrolyzed to acids (e.g. Plowchalk et al 1997) which then may activate the sensory irritant receptor (Nielsen 1991). The chemical reactivity of aldehydes is well known from organic chemistry.…”

Section: Resultsmentioning

confidence: 99%

“…Using a database of 145 volatile organic chemicals inducing the same biological effect, i.e., sensory irritation, it has been demonstrated that the above rule, when used to divide the database into 56 non-reactive and 89 reactive (electrophiles) chemicals, can definitely be a good starting point (Alarie et al 1998) as originally proposed by Ferguson (1939). The same database was used to confirm earlier findings (Abraham et al 1990(Abraham et al & 1994Alarie et al 1995Alarie et al & 1996 that physicochemical descriptors can be used to estimate the sensory irritation potency of non-reactive chemicals, those having a P P ratio >0.1.…”

mentioning

confidence: 83%

“…Sensory irritation occurs via stimulation of trigeminal nerve endings in the nasal mucosa (Alarie 1973a;Nielsen 1991). Such nerve endings are located just a few microns from the surface (Finger et al 1990).…”

Section: Methodsmentioning

confidence: 99%

“…The potency (RD50) of airborne sensory irritants has been expressed as the concentration resulting in a decrease in respiratory rate by 50% in mice, due to the trigeminal reflex (Alarie 1966). Being a receptor-mediated process (Alarie 1973a & b;Nielsen 1991;Nielsen et al 1992) the interaction be- The short distance between the air phase and the trigeminal nerve endings phase (Finger et al 1990), suggests that the assumption about an equilibrium is reasonable. For the other two assumptions, the results of many investigations for both nonreactive and reactive chemicals (Alarie 1973b;Kane & Alarie 1978;Kristiansen et al 1986;Nielsen & Vinggaard 1988;Nielsen & Yamagiwa 1989;Hansen & Nielsen 1994a & b) fitted the formal equation with the apparent dissociation constant, K= I/(KA.…”

Section: Methodsmentioning

confidence: 99%

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A Theoretical Approach to the Ferguson Principle and its Use with Non‐Reactive and Reactive Airborne Chemicals

Alarie

Nielsen²,

Abraham

1998

Pharmacology & Toxicology

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Abstract:The Ferguson principle has been widely used in toxicology to separate or indicate possible mechanisms for acute toxic effects of chemicals. However, this principle has never been adequately tested because of the lack of a database containing a sufficient number of both types of chemicals, non-reactive and reactive, that the Ferguson principle purports to separate. Such a database is now available. In this report a theoretical framework for the Ferguson principle is presented, regarding one of the acute toxicological effects of volatile airborne chemicals: sensory irritation. Previously obtained results on series of non-reactive and reactive chemicals are then used to demonstrate that the Ferguson principle can be extended to reactive chemicals by adding chemical reactivity descriptors to the physicochemical descriptors required by the Ferguson principle. This approach can be successful, provided that specific chemical reactivity mechanisms can be identified for the reactive chemicals of concern. The findings suggest that it is possible to replace the empirical Ferguson principle by formal mechanistic equations which will provide a better foundation for the understanding of the mechanisms by which airborne sensory irritants exert their action.It has been shown (Ferguson 1939;Brink & Posternak 1948;Ferguson 1951; Abraham el al. 1994) that the ratio PRO may be approximately constant (the "Ferguson rule or principle'') for non-reactive volatile organic chemicals giving rise to a particular biological effect. P is the vapour pressure (mmHg or ppm), i.e., the concentration in air of the chemical necessary to induce a given level of effect. P" (same units) is the saturated vapour pressure of the pure liquid. This approach was taken by Ferguson (1939) to demonstrate that toxic indices based on PRO would lie within a relatively narrow range (approximately a constant) for nonreactive chemicals while the measured concentrations, P, would vary widely since the phase distribution phenomenon is not taken into account when using only I?With a P/Po ratio of >0.1 or so, the mechanism by which a chemical induces the biological effect has been defined as physical: due to weak forces attraction between the chemical and the receptor biophase. A ratio <0.1 would indicate a chemical reaction, although physical mechanisms still play a role. This rule could never be tested in a satisfactory manner until recently. Using a database of 145 volatile organic chemicals inducing the same biological effect, i.e., sensory irritation, it has been demonstrated that the above rule, when used to divide the database into 56 non-reactive and 89 reactive (electrophiles) chemicals, can definitely be a good starting point (Alarie et al. 1998) as originally proposed by Ferguson (1939).

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Theoretical Approach to the Ferguson Principle and its Use with Non‐Reactive and Reactive Airborne Chemicals

Alarie

Nielsen²,

Abraham

1998

Pharmacology & Toxicology

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“…(20) One of the first such processes to be studied was that of upper respiratory tract irritation in mice, the most recent and extensive equation [38] The 58 solutes used in Eq. (22) were all 'nonreactive' in that their irritancy effect is induced through essentially a physical mechanism [38][39][40].…”

Section: Glc Datamentioning

confidence: 99%

Connection between chromatographic data and biological data

Abraham

Gola

Kumarsingh

et al. 2000

Journal of Chromatography B: Biomedical Sciences and Applicatio

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There are no previous references to the direct use of GLC data in the correlation of biological processes, but we show that GLC retention data can be used in the correlation of several such processes involving gaseous solutes. There are a number of reports of RP-HPLC and MEKC data being used in the correlation of biological processes, but they are mostly restricted as to the number and type of solute studied.We show that if chromatographic data are used to obtain solvation descriptors for solutes, and if these descriptors are then used in the correlation of biological processes, that this indirect connection is a much more powerful and generally applicable method than is the direct connection between chromatographic data and biological data.

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Peripheral Chemosensory Irritation: Fundamentals, Investigation and Applied Considerations

Ballantyne

2009

General, Applied and Systems Toxicology

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Peripheral chemosensory irritation (PCSI) is a pharmacological effect in which xenobiotics interact with sensory nerve receptors in skin and mucosae to produce local sensation (discomfort, itching, burning sensation or pain), together the development of local reflexes and systemic (autonomic) reflexes. The effects subside after removal of the irritant stimulus and do not result in long‐term adverse sequelae. The principal sites where PCSI effects develop are the eye, respiratory tract and skin. The effects produced are protective in nature. For example, with the eye there is pain, increased lacrimation and blepharospasm; these effects give a biological warning of the presence of a PCSI material in the immediate environment, and are protective in nature. The peripheral sensory effects may underlie some of the characteristics associated with the various types of idiopathic environmental intolerance, including multiple chemical sensitivity. Since the local sensory and reflex effects resulting from exposure to a potent sensory irritation (PSI) substance may be detrimental to safe and efficient working conditions, in many cases they may be used as a basis for assigning airborne occupational exposure limits. This review chapter discusses the nature of the PCSI response, receptor interactions and mechanisms, factors influencing response to PCSI effects, quantitation of the response, methods for measuring the PCSI response and the practical implications and applications of chemosensory irritation.

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Sensory irritation mechanisms investigated from model compounds: trifluoroethanol, hexafluoroisopropanol and methyl hexafluoroisopropyl ether

Cited by 19 publications

References 24 publications

A Theoretical Approach to the Ferguson Principle and its Use with Non‐Reactive and Reactive Airborne Chemicals

A Theoretical Approach to the Ferguson Principle and its Use with Non‐Reactive and Reactive Airborne Chemicals

Connection between chromatographic data and biological data

Peripheral Chemosensory Irritation: Fundamentals, Investigation and Applied Considerations

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