Vaccari D.A., Strom P.F., Alleman J.E. Environmental Biology for Engineers and Scientists

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effective than, the blood–brain barrier. There is an efﬁcient DNA repair mechanism in the

cells that generate sperm, but not in the sperm cells themselves. Blood lead levels in

excess of 41 to 53 mg=dL were associated with reduced sperm count s and infertility.

Other effects include reduced testosterone levels, testicular atrophy, loss of libido, and

impotence. Table 17.6 lists some toxins known to affect the male reproductive system.

Toxic effects on the female reproductive system include reduced fertility due to ovum

loss or prevention of implantation, ovary damage, and early menopause. Appa rently,

before puberty the oocytes are relatively resistant to toxic damage, other than that caused

by ionizing radiation. Cigarette smoking is known to cause early menopause, possibly

because of the PAHs present in the smoke.

Systemic Effects and Toxic Effects in the Blood Some toxins cause the body to

release substances to the bloodstream in harmful amounts. Allergic responses cause

cells to release stored histamine. Besides the bronchial constriction described above,

histamine causes blood vessels to dilate (increase in diameter) and their permeability

increases. Both of these have the effect of reducing blood pressure, which can result

in vascular collapse. These are the events in anaphylactic shock. Another example

of an indirect effect is the relea se of epin ephrine in response to exposure to carbon

tetrachloride.

Hydrogen sulﬁde ðH

SÞ and hydrogen cyanide (HCN) both can be absorbed through

the lungs (although HCN can also be ingested), and both act by poisoning the cyto-

chrome system, bringing aerobic respiration to a halt in every cell in the body. Both

also have strong odors. HCN has a bitter almond odor, but 20 to 40% of the population

is unable to detect it. H

S produces a strong ’rotten egg‘ smell. H

S may be generated by

bacteria in lethal quantities whenever biodegradable sulfur-containing material is pres ent

in conﬁned spaces, such as in sewage manholes or food transport containers. It is often

responsible for particularly tragic accidents with multiple fatalities. A typical scenario is

as follows: A worker enters a conﬁned space such as a tank and collapses in moments

from the exposure. One or more co-workers attempt a rescue and are also overcome.

There have even been cases where professional rescuers wearing a self-cont ained breath-

ing apparatus received lethal doses due to leakage around the mask.

Oxygen is carried in the blood by complexation with hemoglobin in the red blood

cells. The ability to carry oxygen to the tissues can be reduced by several toxins. The

TABLE 17.6 Male Reproductive System Toxins

Physical agents Organic chemicals

Microwaves Alkylating agents

Ionizing radiation Anaesthetic gases

High temperatures Carbon disulﬁde

Social habits Chloroprene

Alcohol ingestion Vinyl chloride

Cigarette smoking Chemotherapeutic agents

Marijuana smoking Dibromochloropropane

Metals Kepone

Lead DDT

Cadmium Female oral contraceptives

Source: Williams and Burson (1985).

728 THE SCIENCE OF POISONS

best known is carbon monoxide, which competes with oxygen for the hemoglobin. The

CO–hemoglobin complex is called carboxyhemoglobin. The ratio of carboxyhemoglobin

to oxygenated hemoglobin depends on the partial pressures of the two compounds as

described by the Haldane equation:

½HbCO

½HbO



ð17:2Þ

where M has a value somewhere from 210 to 245. Thus, if the CO and O

were at equal

concentrations, more than 200 times as much of the hemoglobin would be bound to CO

as to O

. As an application, this equation can be used to determine what partial pres sure

of CO would tie up half of the hemoglobin, a level that could result in coma or death. This

is found by setting the left-hand side of equation [17.2] to 1.0, resulting in

CO;1=2sat

ð17:3Þ

Thus, expressing the partial pressures as a percentage of 1 atm, we get P

CO;

sat

=210 ¼ 21%=210 ¼ 0:1%, which is 1000 ppmv. The relation between percent carb-

oxyhemoglobin and health effects is described in Section 21.5.

Some compounds can reduce the oxygen-carrying capacity of hemoglobin by oxiding

its ferrous (þII) iron atom to the the ferric (þIII) state. This form of hemoglobin,

methemoglobin, does not bind oxygen or carbon monoxide. Nitrite is one of the sub-

stances that do this. It is usually ingested as nitrate either in cured meats or in drinking

water, and then converted to nitrite by intestinal ﬂora. The problem is usually restricted to

infants and causes a disease called methemoglobinemia, or ‘‘blue baby’’ syndrome. The

drinking water standard for nitrate of 10 mg/L is set with this sensitive population in

mind.

Chemical toxins can cause other blood problems: low red blood cell count s (anemia),

low white blood cell counts (agranulocytosis), low platelet counts (thrombocytopenia),

or damage to bone marrow tissue that produces all of the above (aplastic anemia). As

described in Section 17.4.7 on the kidney, some substances cause lysis of red blood

cells, or hemolytic anemia.

Some toxins affect the heart and the blood vessels. High levels of cobalt causes

calcium accumulation in the mitochondria of heart muscle. Lead, mercury, and a number

of other substances damage the endothelium of capillaries in the brain. This causes edema

(swelling) and harms the blood–brain barrier.

17.4.8 Effects at the Individual Level

Often, the under lying physiological mechanism of toxicity is not detected. Instead, gross

organismal effects are observed. Symptoms of toxicity observable at the whole organism

level are, of course, highly varied, depending on the mechanism of damage. The most

signiﬁcant is mortality, the death of the organism. This results, of course, when any of

the previously described effects become serious enough to sufﬁciently impair a vital func-

tion. This can occur at the subcellular level, such as cyanide’s role in halting the electron

transport chain or organophosphates in causing paralysis of the respiratory system. Necro-

sis of selective tissues, such as by carbon tetrachloride in the liver, can eventually impair

TOXIC EFFECTS 729

liver function and cause mortality indirectly. Sometimes the only effect observed will

be weight loss or gain, or indications of gastrointestinal disturbances such as vomiting

or diarrhea.

Behavioral effects may be much easier to detect than underlying physiological effects

in living organisms. Behavioral effects can affect the survivability of an organism in var-

ious ways:

 Response to stimuli, such as temperature or salinity for ﬁsh or avoidance of noxious

chemicals

 Mating behavior

 Feeding behavior

 Locomotor behavior

 Learning ability

 Social behavior, such as territoriality, courtship, care of young, or forming groups

(schooling in ﬁsh)

 Other activities such as burrowing or nest building

Numerous apparatuses have been developed to expose ﬁsh to gradients of physical or

chemical stimuli. The ﬁsh position themselves in the gradient, and their preference is

recorded. For example, blue crabs have been shown in this way to be able to detect

naphthalene at concentrations starting at 10

7

mg=L! A simple test of predatory behavior

involves placing a predator and a prey species, one of which has previously been exposed

to a toxicant, in a tank. After a period of time, the number of prey remaining are counted.

Motor activities include qualitative descriptions of movement such as repetitiveness or

randomness of motion compared to control animal s. Experimental psychology has deve-

loped a large database of behavior with rats, mice, pige ons, and primates. These data are

useful for making comparisons with those animals.

17.4.9 Effects at the Ecological Level

Again, underlying physiological effects have consequences at higher levels of organiza-

tion, beyond the individual, to populations and to relationships between species and even

to effects on the physical and chemical environment. Population effects can be placed into

the following categories:

Population reductions. These may be due to direct toxic effects, elimination of prey, or

to ingestion of prey which have themselves taken up toxins from the environment.

Population increases. There are due to elimination of competitors or predators,

resulting in increases of nontarget species and replacement of one species by

another.

Sublethal effects. These include bioaccumulation, changes in behavior such as

predator–prey relationships, and differential survival and reproduction.

Genetic changes. These include selection pressure for resistance, and the bottleneck

effect, by which the distribution of traits may change signiﬁcantly. Resistance is

particularly troublesome, because it tends to cause users to increase their application

rates, increasing risks to nontarget organisms.

730 THE SCIENCE OF POISONS

Ecosystem effects can be summarized as follows:

Reduction in number of species, in species diversity, and changes in energy ﬂows.

Removal of organisms with longer life-spans and increased predominance of those with

shorter life spans.

Outbreaks of some nontarget species , especially in lower trophic levels. This results

from a disturbance in normal ecological relationships, such as predator–prey,

competition, and symbiosis.

Population instability of predators and parasites at higher trophic levels due to

disturbances at lower trophic levels.

Data showing these effects have been collected from both experimental and accidental

ecosystem exposures to xenobiotics. These show that it is necessary to address not just

acute and chronic toxicity, but also fate and transport of contaminants and impacts on

all the trophic levels in an ecosystem.

All of these effects are associated with either mortality of individual organisms or with

reduced reproductive success. The classic case of the latter is the effect of DDT on birds of

prey, including the American bald eagle. Even though the levels that accumulated in the

birds was below those toxic to the adult, they were lethal in the sense that the birds

became unable to produce young. The pesticide would become concentr ated in the egg

yolks at levels that prevented the chicks from surviving to hatch, or the egg shell produced

by the p arent would be too thin to survive the incubation period.

Organisms with short life spans tend to reproduce rapidly, and rush to ﬁll environ-

mental niches vacated by other species. This lengthens the time to recovery of an affected

ecosystem. Examples of these fast-growing species are various types of ‘‘weed’’ plants

and animals such as the Norway rat.

Physical changes to the environment can result from toxic effects. Changes in plant

distribution can result in erosion, siltation of surface waters, and elimination of animal

habitats such as nesting sites or speciﬁc types of shelter required by certain species.

17.4.10 Microbial Toxicity

Bacteria are among the organisms that are most insensitive to toxic substances. Several

reasons for this are:

 They have much simpler metabolic processes than higher organisms, reducing the

number of ways a toxicant can interfere. For example, organophosphate pesticides

attack acetocholinesterase, which bacteria do not produce. However, toxins that

affect all kinds of organisms, such as cyanide, can also affect bacteria.

 Bacteria can form resistant stages or slow their metabolism to survive adverse

conditions. Thus, many toxicants may stop growth but not kill cells.

 Bacterial membranes are more selective in their transport mechanisms. This is in

contrast to animals, which have specialized transport organs such as the digestive

tract and kidneys.

Thus, if a substance is toxic to bacteria, there is a good chance that it will be even

more toxic to higher organisms. This makes bacteria useful for toxicological screening

TOXIC EFFECTS 731

purposes. An exception, of course, is the antibiotics, which are selected to inhibit specia-

lized metabolic processes in bacteria.

Even if a toxic substance does kill or inhibit a type of bacteria, it may be difﬁcult to

measure the effect for several reasons:

 Because bacteria are capable of rapid growth, if only a part of the population is

killed, the remainder can quickly reproduce to replace them.

 Bacteria are specialized in metabolic mechanisms, and related genera may have

related capabilities. Thus, if one species is inhibited, a previously minor relative may

grow rapidly to occupy the niche. An exception is the nitriﬁers. These are typically

slow growing and slow to take advantage.

 In any nonsterile environment, bacteria are ubiquitous and diverse. That is, there will

be many different strains with overlapping metabolic capabilities and many with

different capabilities. Thus, there will usually be one or more strains available that

are resistant to an introduced toxicant and able to take advantage of available

nutrients to grow.

These factors argue against the likelihood of the effectiveness of bioaugmentation.

Bioaugmentation is the practice of inoculating biological treatment processes, such as

activated sludge or septic tanks, with bacterial cultures to replace ‘‘killed’’ bacteria or

to supply organisms capable of degrading refractory substances.

PROBLEMS

17.1. The LC

of copper in mg=L to salmonid ﬁsh vs. hardness (H) in mg CaCO

=Lis

given by equation (17.1). Use this equation to compute the LC

value for a soft

water, H ¼ 50 mg CaCO

=L, and for a hard water, H ¼ 350 mg CaCO

=L.

17.2. What is the receptor for a carcinogenic initiator? For a promoter?

17.3. By what mechanism could a free radical cause cancer as an intiator; by what

mechanism as a promoter?

17.4. Name a carcinogen that would be considered a local toxin.

17.5. How many toxic effects of ethanol can you think of?

17.6. Name one chronic and one acute effect of alcohol on humans. Do the same for

chloroform.

REFERENCES

Cavenee, W. K., and R. L. White, 1995. The genetic basis of cancer, Scientiﬁc American, March.

Connell, D. W., and G. J. Miller, 1984. Chemistry and Ecotoxicology of Pollution, Wiley, New York.

Davis, D. Lee, and H. L. Bradlow, 1995. Can environmental estrogens cause breast cancer? Scientiﬁc

American, October.

Klaassen, C. D., M. O. Amdur, and J. Doull (Eds.), 1996. Casarett and Doull’s Toxicology: The Basic

Science of Poisons, 5th ed., McGraw-Hill, New York.

732

THE SCIENCE OF POISONS

LaGrega, M. D., P. L. Buckingham, and J. C. Evans, 2001. Hazardous Waste Management, McGraw-

Hill, New York, Chapters 5 and 14.

Landis, W. G., and Ming-Ho Lu, 1995. Introduction to Environmental Toxicology: Impacts of

Chemicals upon Ecological Systems, Lewis Publishers, Chelsea, MI.

Lu, F. C., 1991. Basic Toxicology: Fundamentals, Target Organs, and Risk Assessment, 2nd ed.,

Hemisphere Publishing, Bristol, PA.

Masters, G. M., 1998. Introduction to Environmental Engineering and Science, Prentice Hall, Upper

Saddle River, NJ.

Newman, M. C., 1998. Fundamentals of Ecotoxicology, Ann Arbor Press, Ann Arbor, MI.

Rand, G. M., and S. R. Petrocelli, 1985. Fundamentals of Aquatic Toxicology: Methods and

Applications, Hemisphere Publishing, New York.

Simpson B. B., and M. C. Ogorzaly, 1995. Economic Botany: Plants in Our World, McGraw-Hill,

New York.

Weast, R. C. (Ed.), 1979. CRC Handbook of Chemistry and Physics, 60th ed., CRC Press, Boca

Raton, FL.

Williams, P. L., and J. L. Burson (Eds.), 1985. Industrial Toxicology: Safety and Health Applications

in the Workplace , Van Nostrand Reinhold, New York.

REFERENCES 733

FATE AND TRANSPORT OF TOXINS

The ability of a toxin to produce an effect depends on factors other than its ability to react

with a receptor. These include factors that inﬂuence how much of the toxin actually

arrives at the receptor. Physicochemical parameters describe the equilibrium distribution

of substances among phases in the environment and within organisms. However, the

environment and organisms are often far from equilibrium. Therefore, we need to take

a kinetic approach, one that describes the rates at which substances move within organ-

isms. In the next few sections we focus on the fate and transport of substances within

organisms, or pharmacokinetics. In later sections we discuss transport among compart-

ments of the environment and various parts of the ecosystem. Environmental transport is

described using many of the same principles and methods as used here.

The way that a chemical is distributed in the environment and within an organism var-

ies with physicochemical properties that are independent of its toxicity. Toxins may be

absorbed by different mechani sms and by different routes, such as by inhalation or inges-

tion, each wi th its own efﬁciency at delivering the toxin. Once absorbed, the toxin ﬁnds its

way to various parts of an organism, including storage sites. The organism can eliminate

the toxin by biochemical reactions or excretion, or may convert it to a more toxic sub-

stance. These processes can be described mathematically, giving models that can be

used for understanding and predicting the phenomena.

18.1 PHYSICOCHEMICAL PROPERTIES

Besides the obvious fact that the structure of a chemical determines how it reacts chemi-

cally with the receptor, structure affects its equilibrium distribution in the environment

and within organisms. Here we describe the key physicochemical properties affecting

Environmental Biology for Engineers and Scientists, by David A. Vaccari, Peter F. Strom, and James E. Alleman

734

this distribution, which are used in Section 18.7 in our discussion of pharmacokinetics and

environmental modeling.

The properties we are interested in here all relate to the tendency for a chemical to

distribute itself between two connected phases. The phases involved may include air,

water, soil, or sediment in the environment, and tissues, membranes, lipids, and so on,

in organisms. The molecules of a chemical will be distributed according to the physico-

chemical attractions they have for the other molecules surrounding them in each phase.

The physicochemical attractive forces are the same as those described in Section 3.3: van

der Waals, dipole moment, hydrogen bonds, and so on. The process by which a chemical

distributes itself between two phases is called partitioning.

The equilibrium between two phases is described by exactly the same thermodynamics

as was developed for biochemical reactions in Chapter 5. In phase transfer the ‘‘reaction’’

is comparatively simple:

compound in phase A () compound in phase B

This leads to a deﬁnition of the phase equilibrium constant, which states that the com-

pound simply distributes itself between the two phases at a constant ratio, called the parti-

tion coefﬁcient, K

ð18:1Þ

where C

and C

are the concentrations of the compound in phases A and B, respectively.

(For use in partition constants, the concentrations can be expressed either in molar or mass

concentration units.)

One of the most basic partition parameters describing a chemical is its vapor pressure,

. This is the partial pressure at a given temperature that a chemical will have in equili-

brium with its pure liquid or solid phase. For example, if a vial is ﬁlled partway with ben-

zene liquid and sealed, the benzene will vaporize int o the airspace until its partical

pressure reaches an equilibrium value, which is the vapor pressure. The vapor pressure

can be considered to be a measure of the attractive forces among a compound’s molecules.

The stronger the attraction, the lower the vapor pressure. A high vapor pressure can facil-

itate exposure to toxic subst ances by inhalation or atmospheric transport.

Because it is such a basic property, the vapor pressure can serve as a sort of reference

concentration for comparison wtih concentrations in other phases. To be more precise, the

concentrations in different phases can be converted to units of fugacity, which are equiva-

lent to gas-phase partial pressure under ideal gas conditions. Put another way, the fugacity

can be thought of as the partial pressure of a substance in equilibrium with whatever con-

centration and phase is under consideration. The vapor pressure, then, corresponds to a

reference fugacity, or the concentration in any phase in equilibrium with the pure liquid.

Some investigators use fugacity in place of concentration units to express the amounts of a

contaminant in the environment.

At ambient pressures, the ideal gas law is very accurate for both pure and mixed gases

and rarely needs correction. Expressed in terms that relate the partial pressure of com-

pound i, P

, to concentration in mass/volume units, C

, and to temperature, T, and the

gas law constant, R, the ideal gas law is

M¼C

RT ð18:2Þ

PHYSICOCHEMICAL PROPERTIES 735

where M is the molar mass. Concentrations of chemicals in air may be expressed as mole/

volume, mass/volume, or commonly as volume/volume. The latter is usually given as the

parts per million by volume (ppmv). In ideal gas mixtures, the following expression

relates ppmv with the partial pressure in equation (18.2):

ppmv ¼ 10

ð18:3Þ

where P

is the total pressure. At 20



C and 1.0 atm total pressure, we can combine equa-

tions (18.2) and (18.3):

ðmg=m

Þ¼ppmv 

Mðg=molÞ

ð18:4Þ

Example 18.1 What would be the concentration of benzene in air, C

, in a poorly venti-

lated room containing an unsealed drum of liquid benzene?

Answer In this case the partial pressure of the benzene in the air wi ll be approxi-

mately equal to the vapor pressure. The vapor pressure of benzene is 95.2 mmHg at



C. From equation (18.2) (note that 1.0 atm ¼ 760 mmHg):

95:2mmHg

760 mmHg=atm

78:11

mol



mol  K

0:08205 L  atm



298:15 K



¼ 0:40 g=L

Example 18.2 The ambient air quality standard for ozone (M¼48 g=mol) is

0.120 ppmv. What is the concentration in mg/m

Answer From equation (18.3), we have P

¼ P

 ppmv/10

¼ 1:2  10

7

atm. From

equation (18.2), C

¼ P

M=RT ¼½ð1:2  10

7

atm) (48 g/mol)]/(0.08205 L/atm 

mol K 293KÞ¼2:40  10

7

g=L ¼ 0 :240 mg=m

Another important partition coefﬁcient is Henry’s constant, H

, which describes how

a chemical distributes itself between vapor phase and a liquid mixture (usually water solu-

tion in the cases of interest here). The amounts in the vapor and water phases can be mea-

sured in numerous way s, including partical pressure, fugacity, mole fraction, or molar or

mass concentration. When expressed as molar or mass concentration units, Henry’s con-

stant is

ð18:5Þ

where C

is the gas-phase concentration and C

is the concentration in the liquid, both

phases at equilibrium with each other. Whereas the vapor pressure indicates the tendency

of a compound to distribute itself between its pure liquid and the vapor phase, Henry’s

constant relates to the distribution betwee n a solvent and a vapor. The less the attraction

between solute and solvent molecules, the higher the Henry’s constant value. In fact,

because vapor pressure represents the tendency to be in the gas phase, and aqueous

solubility the tendency to be in the aqueous phase, Henry’s constant can be estimated

as the ratio of vapor pressure to aqueous solubility (with appropriate unit conversions).

Example 18.3 The OSHA standard for toluene states that the average air concentration

that a worker may be exposed to during an 8-hour work shift may not exceed 200 ppmv.

736 FATE AND T RANSPORT OF TOXINS

If someone were working in a poorly ventilated enclosed space over a wet well, what is

the highest permissible concentration of toluene in the water so that if the air were in equi-

librium with the water, it would not exceed the OSHA standard? The molar mass of

toluene is 92.13 g/mol, and H

¼ 0:265.

Answer Using equations (18.3) and (18.4), we have

 ppmv

1 atm ð200 ppmvÞ

ppmv



92:13 g=mol

0:08205 L  atm=mol  K



1000 mg=g

298:15 K



¼ 0:753 mg=L

From equation (18.5),

0:753 mg=L

0:265

¼ 2:84 mg=L

The most important solvent in biological systems is, of course, water. Many organics,

such as ethanol, mix with it readily. Other substances are immiscible with the water. That

is, two separate phases are formed at equilibrium, the aqueous phase consisting mostly

of water and the organic phase consisting mostly of the organic. The concentration of

the organic compound in the water in this situation is the aqueous solubility (c

). For

example, water in contact with liquid benzene dissolves 1750 mg per liter of water. Sub-

stances tend to be more soluble in water: As polarity increases, molar mass decreases if

they ionize or if they are capable of forming hydrogen bonds. Aqueous solubility and

vapor pressure are the key physicochemical parame ters governing the fate and transport

of many synthetic chemicals. In fact, Henry’s constant is the ratio of vapor pressure to

aqueous solubility.

As their name implies, hydrophobic compounds have very low aqueous solubility.

These compounds distribute themselves between a hydrophobic phase and a hydrophilic

phase. In biological systems this means lipids and water, respectively. Experimentally, this

relationship is determined using a surrogate compound for the lipids: octanol. Octanol is

fairly nonpolar, although not extremely so. Water has an appre ciable solubility in it (21%

as a mole fraction, or about 31.5 g/L), yet water and octanol do form distinct phases. In the

laboratory a solute can be added to a vial containing both water and octanol and allowed

to come to equilibrium. The solute will distribute itself between the two phases in a con-

stant proportion similar to how it might be distributed between, say, blood plasma and

plasma membrane lipids. The molar concentrations of solute in the octanol and water

in this experiment, c

and c

, respectively, can be determ ined, and their ratio is a phy-

sicochemical property of the solute called the octanol–water partition coefﬁcient, K

ð18:6Þ

A number of empirical correlations have been developed to estimate K

from

aqueous solubility. One such relationship (Chiou et al., 1983) is (the aqueous solubility,

, must be given in units of molarity):

log K

¼ 0:710  0:862 log c

ð18:7Þ

PHYSICOCHEMICAL PROPERTIES 737