Page 664 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

VetBooks.ir Chapter 48

Toxic Gases and Vapors

Rhian Cope

INTRODUCTION system, once the equilibria are established, no net absorp-
tion will occur unless there is loss from the system (i.e.,
For the purposes of this chapter, a gas is defined as a state
metabolism), reaction with tissue molecules, or excretion
of matter consisting of molecules that have neither a
through nonrespiratory pathways (e.g., renal excretion). It
defined volume nor shape at standard temperatures and
is critical to note that just because the equilibria have
pressures. A vapor is the gaseous phase of substances that
been established does not mean that the concentrations in
are either solid or liquid at standard temperatures and
the different compartments are equal. Rather, once the
pressures. As a general rule, the toxicology of gases is equilibria are established, the concentration ratios
also broadly applicable to the toxicology of vapors.
between the various compartments will remain constant
This chapter is divided into two sections: general prin-
provided that saturation of the system and/or other system
ciples and specific toxic gases. The general principles sec-
perturbations do not occur, i.e., the air:blood:tissue(s)
tion covers gas toxicokinetics and basic dosimetric
concentration ratios remain constant.
adjustments for human risk assessment. The specific toxic
Absorption of the gas will continue if “losses” from the
gases section covers specific toxic gases that are of veteri-
system occur. If the substance is lost through metabolism,
nary clinical and veterinary occupational relevance (car-
the rate of continued absorption once the equilibria have
bon monoxide (CO), hydrogen sulfide, oxides of nitrogen
been established is effectively the rate of metabolism of
(silo filler’s disease), gaseous ammonia (including anhy-
the substance. This mass balance relationship is the basis
drous ammonia), and smoke inhalation).
of closed respirometry measures of oxygen consumption
and metabolic rate (pioneered by Laplace and Lavoisier in
GENERAL PRINCIPLES the 1770s). If the substance is lost from the system solely
through nonrespiratory excretion once the equilibria have
Toxicokinetics been established, the rate of continued absorption is equiv-
alent to the rate of nonrespiratory excretion.
Absorption and Distribution
If the concentration of the gas in the tissue(s) is higher
Depending on their physicochemical properties, gases can
than that in the respiratory airspaces (e.g., if the inhalation
produce site-of-first-contact effects or systemic toxicity
exposure is stopped or the concentration in the inhaled air
following absorption or a combination of both. The usual
is reduced), the net diffusive force will drive the move-
driving force for the systemic absorption (i.e., entry into
ment of the gas from the tissue(s) into the air. An exam-
the central circulation) and tissue distribution of inhaled
ple is the excretion of carbon dioxide produced by
gases is diffusion down concentration gradients (although
aerobic metabolism in the tissues that is largely driven by
cellular uptake and protein binding can alter this dynamic;
simple diffusion. This is also the basis for the net excre-
Rozman and Klaassen, 2001; Witschi and Last, 2001; tion of a nonmetabolized gas once exposure has ceased,
Renwick, 2008; Valentine and Kennedy, 2008). These e.g., the recovery from gaseous anesthesia.
relationships can be described at a high level by a series In normal circumstances, gas diffusion is not rate lim-
of simplified toxicokinetic equilibria and related equilib-
iting for the systemic absorption because: (1) generally
rium constants (K):
ionized, hydrophilic molecules that are apt to be
K K diffusion-limited across biological membranes have low
Air 2 Systemic Circulation 2 Tissues
volatility, i.e., their concentration in normal air is usually
The absorption of a gas will continue until equilibria very low; (2) alveolar type I pneumocytes are very thin
are established in the various compartments. In a closed and are in intimate contact with the pulmonary capillaries,
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00048-9
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