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results of animal bioassays are routinely extrapolated to risk levels of 10

6

, as described

in Section 19.3.1.

Rapid screening tests have been developed using especially sensitive strains of ani-

mals. Mouse skin is sensitive to tumor formation from topical application, apparently

because it is active in biotransformation. Strain A mice spontaneously develop lung

tumors in 100% of animals by 24 months of age. They can be used to determine carcino-

genicity in tests as short as 12 to 24 weeks. Several rat strains have been developed with

naturally high rates of breast cancer.

Biomarkers are detectable biochemical changes. A variety has been developed that can

discriminate between cancer initiation, promotion, and progression. The binding of che-

micals such as benzo[a]pyrene to DNA can be detected by use of radiolabeled compounds

or by radioimmunoassay. Promotion has been correlated with increased prostaglandin

synthesis and with changes in the levels of some enzymes, such as ATPase. A variety

of chemicals is produced by malignant cancer cells. Fetal liver and hepatocarcinoma,

and sometimes other organs, produce a-fetoprotein (AFP). Mammary carcinomas are

associated with a group of chemicals, and prostate cancer is marked by elevate d levels

of prostate-speciﬁc antigen (PSA), which can be detected by a blood test.

A positive control is a test group that receives a known carcinogen at a dose that is

expected to produce a signiﬁcant response. This provides a check on the sensitivity of the

organisms used in the test and on the overall tes ting procedure.

An important problem in the testing of carcinogens is that some may only be initiators

and others only promotors. Thus, it may be necessary to test a chemical with a known

initiator, and separately with a known promoter, to detect carcinogenicity. Since initiators

are genotoxic, compounds that test positively for mutagenicity should also be suspected of

carcinogenicity.

Teratogen tests are commonly done with pregnant rats, rabbits, mice, and hamsters, but

also with pigs, dogs, and primates. An assay using the developing chick embryo was once

widely used but was found to produce too many false positives. Because teratogenesis is

sensitive to time of administration, in tests a chemical is usually dosed continuously over

the period of organ formation. Fetuses are removed surgically about one day before their

expected birth so that dead fetuses can be counted. The fetuses are examined for abnorm-

alities. Some of the pregnant females may be allowed to deliver so that delayed effects can

be discovered.

Extrapolation of teratogenesis in animal models to humans is particularly susceptible

to false negatives. The most potent human teratogen known is thalidomide, which acts at a

dose of 0.5 to 1.0 mg/kg. However, it has no teratogenic effect in rats and mice at 4000

mg/kg. On the other hand, acetylsalicylic acid (aspirin) is known to be safe for use by

pregnant humans but is a strong teratogen in rats, mice, and hamsters.

20.1.13 Mutagenic ity Testing and In Vitro Tests

A variety of mutagenicity tests has been developed. They can be categorized as tests that

detect gene mutations, chromosome effects, DNA repair and recombination, or others.

The others include tests for transformation of mammalian cells into malignant cancer

cells in vitro.

Gene mutation tests detect mutations directly. They may be conducted in vitro or

in vivo, and with prokaryotic or eukaryotic organisms. One of the best known is the

Ames test. This test uses a strain of Salmonella typhimurium that has been mutated

798 FIELD AND LABORATORY TOXICOLOGY

artiﬁcially so that it cannot synthesize the amino acid histidine. In the test, this organism is

cultured in a histidine-deﬁcient medium with the chemical being tested. Mutagens cause a

reverse mutation, again allowing the organism to produce its own histidine. The presence

of growth in the histidine-deﬁcient medium thus serves to indicate the occurrence of a

mutation. Since many mutagens require bioactivation, microsomes extracted from animal

livers are added to the medium. These supply active cytochrome enzyme systems. Similar

tests have been developed using eukaryot ic yeast cell cultures and mammalian cell

cultures.

(The developer of this test, Bruce Ames, is an outspoken critic of the way that tests are

used to identify carcinogens. He states: ‘‘The effort to eliminate synthetic pesticides

because of unsubstantiated fears about residues in food will make fruits and vegetables

more expensive, decrease consumption, and thus increase cancer rates. The levels of syn-

thetic pesticide residues are trivial in comparison to natural chemicals, and thus their

potential for cancer causation is extremely low.’’)

A type of in vivo gene mutation test is the host-mediated assay. In this test, cells that

are susceptible to reverse mutation (whether bacterial or eukaryotic) are injected with the

toxicant into a live animal, such as a mouse. After several hours the animal is sacriﬁced

and the injected cells are cultured to detect mutat ions. This has the advantage of using all

the biotransformation mechanisms of the living animal.

Mutations can also be detected directly in test animals. The most popular is the fruit ﬂy

Drosphila melanogaster, but tests have also been developed to detect mutations in mice.

Chromosomal effects include structura l aberrations such as deletion or duplication of

chromosomes, or translocation, involving switching of sections between different chro-

mosomes. These are conducted either in vitro using mammalian cell cultures or in vitro

with Drosophila sp. or mammals. In either case the effect is detected by microscopic

examination a period of time after dosing the system with the toxicant.

The third type of mutagenicity test involve the DNA repair mechanisms to detect muta-

tions. Some strains of Escherichia coli and Bacillus subtilis are deﬁcient in repair

enzymes. Their growth will be inhibited relative to normal strains when mutations

occur, and this inhibition can be detected by an assay. In another test of this type,

DNA synthesis stimulated by mutations can be detected in human cell culture by the

uptake of radioactive thymidine.

20.1.14 Extrapolation from Animals to Humans

Differences in the toxicity of speciﬁc substances between humans and laboratory animals

cause considerable uncertainty in the application of animal data to humans. The differ-

ences can sometimes be isolated to differences in absorption, distribution, biotransforma-

tion, and excretion. For example, 2-naphthalamine is converted to the carcinogen 2-

naphthyl hydroxylamine by dogs and humans. This is excreted by the kidneys and causes

bladder cancer. However rats, rabbits, and guinea pigs do not excrete this metabolite and

do not get bladder cancer from the original compound. Ethylene glycol is metabolized by

two pathways with the separate end products oxalic acid or CO

. Cats metabolize more of

the ethylene glycol to oxalic acid, whe reas rabbits produce more CO

. Consequentl y,

ethylene glycol is more toxic to cats than to rabbits. The LD

for dioxin (TCDD) is

5 mg/kg in hamsters but only 0.001 mg/kg in guinea pigs. This large range in toxicity

between species has produced considerable controversy over the setting of dioxin

standards for humans.

TOX ICITY TESTING 799

Because of this uncertainty, the use of animal toxicity data for humans is often attacked

as not being ‘‘scient iﬁcally valid.’’ However, there are degrees of scientiﬁc validity, and

there is certainly correlation between the toxicities to two different mammalian species.

We must ask ourselves whether it would be prudent to expose large populations of

humans to subst ances that harm rats if we don’t have speciﬁc information that it would

be safe to do so.

The U.S. EPA suggests selecting data from tests on animals that respond most like

humans. If this type of data is not available, all acceptable data should be used, with

emphasis placed on the most sensitive species, strain, and sex.

Animal data are scaled to human dosages by the ratio of either body mass or body sur-

face area. Body surface area is preferred by the U.S. EPA. It is more conservative, produ-

cing risks that are higher by a factor of 5 when extrapolating from rat data, and 12 times

higher when using mouse data. Furthermore, safety factors are usually applied to extra-

polate from animals to humans to provide additional conservatism.

20.2 EPIDEMIOLOGY

The exposure of people to toxins in the workplace or in the environment can result in an

unintentional, uncontrolled ‘‘experiment.’’ This kind of information can be exploited to

ﬁnd information that could not be found in the laboratory. Laboratory experiments

often cannot reproduce the large number of exposures, and experiments with humans

are closely constrained by ethical considerations. Epidemiology includes techniques to

analyze ‘‘natural experiments.’’ These kinds of studies are termed observational, in con-

trast with experimental. For example, the effect of ﬂuoride on humans can be studied by

comparing the effect on populations with conce ntrations in their drinking water.

Epidemiology is the study of the aggregate occurrence of disease in human popula-

tions. It is not concerned speciﬁcally with occurrence in individuals. Thus, it often uses

the language and tools of probability and statistics to answer questions such as: Is a group

of workers exposed to pesticides in a manufacturing plant more likely to get a certain type

of cancer? If some people at a picnic came down with food poisoning, which food is most

likely to have caused it? If a certain commun ity has more cases of childhood leukemia

than the state average, what is the probability that the ‘‘cluster’’ occurred by chanc e?

Epidemiological studies may ﬁnd correlations between one or more factors and dis-

ease. Such correlations are suggestive of causation but are not proof. Correlation may

occur by chance or because the factor and the result are both caused by another factor.

For example, a correlation was found between stork populations in communities near

Hamburg, Germany, and the human birth rate. Such a correlation might suggest that storks

bring babies! The real reason for the correlation was because there were more storks in

rural areas than in developed ones, and people in rural communities tended to have larger

families.

A correlation turns to proof when additional information supports causation, such as

discovery of a fundamental mechanism that predicts such causation, or evidence from a

controlled experiment. Hill’s criteria (Table 20.3) is a list of factors that provides support

for causation. Not all of the criteria need to be positive, although the more that are satis-

ﬁed, the stronger is the support. Also, negative results do not rule out a causal relationship

but may indicate an incomplete understanding of the relationship.

800 FIELD AND LABORATORY TOXICOLOGY

One of the simplest types of epidemiological analysis performed is a comparison of

occurrence rates. The number of occurrences can be displayed in tabular form:

With Disease Without Disease

Exposed ab

Not exposed cd

The relative risk, r, is the ratio of the probability of exposed persons contracting the

disease to the probability for unexposed persons. It is computed from the table as

r ¼

a=ða þ bÞ

c=ðc þ dÞ

ð20:1Þ

Example 20.1 Consider as an example the cancer risk associated with cigarette smok-

ing. Approximately one-fourth of the adult U.S. population smokes. About 20% of the

U.S. population dies of cancer. What is the rate for smokers, and what is the relative

risk for a smoker getting cancer compared to a nonsmoker?

Answer We will select as a basis a þ b ¼ 1000 smokers. If this is one-fourth of the

total population, there are c þ d ¼ 3000 nonsmokers, and 4000 is the total basis popula-

tion. The 20% of the total population that dies from cancer is represented by 800 persons,

leaving 3200 without cancer. The risk for nonsmokers is 10%, or c ¼ 300 persons, and

therefore there are 2700 nonsmokers without cancer. By difference, a ¼ 500 and

b ¼ 500. The rate comparison table will be:

With Cancer Without Cancer Total

Smoker 500 500 1000

Nonsmoker 300 2700 3000

Total 800 3200 4000

Now the probability of a smoker getting cancer can be calculated to be a=ða þbÞ¼0:50,

and the relative risk is thus 0:50=0:10 ¼ 5:0. In other words, smokers are ﬁve times more

likely to die from (any kind of) cancer in their lifetime than are nonsmokers. (For lung

cancer in particular, the relative risk is about 10 to 15!)

Statistical techniques can reﬁne relative risk calculations. Suppose that the relative risk

ratio was only 1.1. Does that represent a signiﬁcant increase in prevalence? If the total

number of people in each group were large enough, such a ratio could be statistically

TABLE 20.3 Hill’s Criteria for Causal Relationships

1. Strength: A high magnitude of effect is associated with exposure to the stressor.

2. Consistency: The association is observed repeately under different circumstances.

3. Speciﬁcity: The effect is diagnostic of a stressor.

4. Temporality: The stressor precedes the effect in time.

5. Presence of a biological gradient: Greater amount of stressor produces a stronger effect.

6. Mechanism: A plausible mechanism of action exists.

7. Coherence: The hypothesis does not conﬂict with knowledge of natural history and biology.

8. Experimental evidence: A controlled experiment supports the relationship.

9. Analogy: Similar stressors cause similar responses.

EPIDEMIOLOGY 801

signiﬁcant. In a small experiment, such a ratio is more likely to occur by chance. Statis-

tical hypothesis-testing methods can estimate whether that chance is signiﬁcant. Other sta-

tistical techniques used in epid emiology include analysis of variance (ANOVA),

multilinear regression, and logistic regression.

Because the data used by epidemiologists are usually not generat ed in controlle d

experiments, special techniques have been developed to establish the kind of information

produced by controls. The example given above is a cross-sectional study, in which dis-

ease in a single population is studied at one particular time. The prevalence of disease in

subgroups possessing different factors is determined and analyzed. A case–control (or

retrospective) study is similar, but begins with one population that has a disease and

then locates another control or comparison group that is without it. A cohort (or prospec-

tive) study starts with a group that is free of disease and follows it over a period of time,

measuring which individuals contract the disease. Measurements are made of various

potential risk factors, and at the end of the period the prevalence of disease is correlated

with those factors. Retrospective and prospective are also used in another sense: The for-

mer is a study that is done on data collected previously, whereas the latter is a study done

on data after the beginning of, and explicitly for, the study.

PROBLEMS

20.1. Typical carcinogenic toxicity tests can only detect substances that will cause at least

10% response in the tes t animals. In terms of carcinogenic toxicity (ED

) and

noncarcinogenic toxicity (MTD), what circumstances would make the carcinogeni-

city of a substance undetectable by a bioassay? What could be done about this

situation?

20.2. What are the advantages and disadvantages of using ﬁsh as an aquatic testing

organism in place of Daphnia?

20.3. The relative risk for cancer for a smoker compared to a nonsmoker increases with

the number of years of smoking. The estimated risk of dying from lung cancer in a

single year for a 70-year-old who has been smoking for 50 years is 649 per 100,000

people. This is 27 times the risk for a 70-year-old nonsmoker. What is the risk for

the population of 70-year-olds as a whole, assuming that one-third of the population

smokes?

REFERENCES

Ames, B. N. The Causes and Prevention of Cancer, http://www.ultranet.com/jkimball/Biology-

Pages/A/Ames_Causes.html.

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

Chemicals upon Ecological Systems, Lewis Publishers, Boca Raton, FL.

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

Hemisphere Publishing, Bristol, PA.

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.

802

FIELD AND LABORATORY TOXICOLOGY

TOXICITY OF SPECIFIC SUBSTANCES

Here we will summarize information relevant to toxicity for substances classed together in

various ways, such as by chemical or physical properties (metals, hydrocarbons, radio-

nuclides), by usage (pesticides or solvents), or by medium (air or water pollution). For each,

we discuss brieﬂy some of the more important anthropogenic sources of exposure and their

physical and chemical properties, fate and transport, and toxic mechanisms and effects.

21.1 METALS

Metals are unique toxins. They are neither created nor destroyed (neglecting nuclear reac-

tions), yet they readily change form and activity. A subgroup in which we are most inter-

ested is the heavy metals. Heavy metals are those with atomic number 22 to 34 and the

elements below them in the periodic table, plus the lanthanides and actinides. Metals are

widely and unevenly dispersed in the environment. Human act ivities that result in expo-

sure to signiﬁcant amounts of metals include mining and smelting operations, metal plat-

ing, fuel combustion, leather tanning, and their use in products from pigments to pipes.

Some metals are essential nutrients but are toxic at higher levels. Examples include

chromium, cobalt, copper, iron, selenium, and zinc. Even arsenic may be required.

There are three main mechanisms of toxicity for metals:

1. Complexation with proteins, especially with sulfhydryl groups of cysteine, resulting

in enzyme disruption

2. The same complexation mechanism as (1), but affecting other proteins, such as

those embedded in membranes

3. Competition with essential metals, such as enzyme cofactors

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

803

Metals are excreted by the kidney, by reversing absorption in the intestines, and by

enterohepatic circulation. Because methylmercury concentrates in the latter pathway, the

mercury can be removed by oral administration of adsorbents such as activated carbon.

Some aquatic plant and animal species growing in contaminated areas have been

observed to develop tolerance for copper and zinc. Animals respond to cadmium, copper,

and mercury by producing the low-molar-mass protein metallothionein in the liver. The

metallothionein binds to thes e metals and to zinc, and transports them to the kidney for

storage. Additional dosages of cadmium or mercury can displace the less toxic zinc or

copper, resulting in less harm than the cadmium or mercury would otherwise cause.

Copper has many sources, including its use in drinking water pipe s and its deliberate

addition to surface water as an algicide. Copper is essential for many enzymes. However,

higher animals have mechanisms to conserve it and othe r essential trace metals during

periods of deﬁciency, and increase excretion at higher dosages. Copper is also critical

to plant life, playing a role in electron transport in photosynthesis. It is also very toxic

to aquatic plants, accounting for its use as an algicide in recreational lakes and pools.

Cadmium is a particularly toxic metal. Sources of exposure include wastewater pro-

duced in metal plating, sewage sludge applied to plants, smelting, and other occupational

exposures. Cigarette smoking is an im portant source and may double the average body

burden. Cadmium becomes complexed with metallothionein and stored in the kidney,

where it accumulates over a lifetime. It is excreted very slowly, having a half-life of

about 20 years. Damage occurs when a ‘‘critical concentration’’ of about 200 to

300 mg/g occurs in the kidney. It affects proximal tubules, reducing resorption of glucose

and amino acids, and causing hypertension (high blood pressure). Inhalation can cause

ﬁbrosis, chronic bronchitis, and emphysema. Prostate cancer has been reported in occu-

pational exposures. Calcium is lost, causing bone disorders, including pain, osteoporosis,

and deformities. In the over 200 enzymes that require zinc as a cofactor, cadmium can

displace the zinc competitively. Zinc is also a metabolic antagonist of cadmium. There-

fore, high zinc intakes give some protection against cadmium toxicity.

Mercury is released to the environment by the burning of fossil fuel and refuse. It was

formerly a major pollutant generated by the chloro-alkali industry. Food has about 5 to

20 mg/kg, except ﬁsh: Tuna and swordﬁsh range from 200 to 1000 mg/kg. In the environ-

ment, mercury (Hg) is oxidized to inorganic ions. Anaerobic bacteria convert it to organic

mercury, especially methylmercury or dimethylmercury. Organic mercury is much more

toxic, since it is more readily absorbed. Dimethylmercury is volatile and can escape to

the atmosphere from contaminated water and sediment. In the body, methylmercury is con-

verted to the divalent inorganic form. Mercury has a very high afﬁnity for sulfhydryl groups

and thus can affect almost any enzyme and membrane-bound proteins. The effect on mem-

branes is to increase their permeability to sodium and potassium, affecting cell osmolarity.

Inorganic mercury is toxic to the kidney. Organic forms (methyl- or ethylmercury) target the

nervous system. Divalent mercury is corrosive. If ingested, it causes abdominal cramps and

bloody diarrhea, followed by renal damage. Calomel (monovalent or mercurous chloride) is

less toxic but is associated with skin reactions. Elemental mercury vapor is an occupational

hazard affecting the central nervous system. Neurological symptoms appear at exposure to

concentrations as low as 0:05 mg Hg=m

. The half-life for elimination of ingested mercury

in seals, ﬁsh, and crabs has been measured to range from 267 to 700 days.

Lead is found in batteries, gasoline additives, paint, lead pipe, and brass ﬁxtures. Many

uses have been phased out recently, particularly indoor paint, gasoline, and pipe solder.

Even without the lead pipe and pipe solder sources, brass remains an important source in

804 TOXICITY OF SPECIFIC SUBSTANCES

plumbing systems. This is because brass ﬁxtures are made with about 8% lead to improve

machinability. Inorganic lead affects heme; organic lead affects the nervous system. Ane-

mia is found at a blood lead level of 50 mg/dL; enzyme effects are found at as low as 10.

Above 80 mg/dL (70 in children) encephalophathy can occur with symptoms including

vomiting, lethargy, irritability, and so on, and possibly proceeding to coma and death. In

children, a moderate exposure can produce measurable mental defects; 40 to 50 mg/dL can

result in hyperactivity, a decrease in attention span, and a slight reduction in IQ score. In

occupational exposures, 40 mg/dL can cause peripheral neuropathy, nerve damage caus-

ing numbness and the classic symptoms ‘‘footdrop’’ and ‘‘wristdrop.’’ A decreased cal-

cium intake causes lead to redistribute from storage in the bone, where it is harmless, to

the more vulnerable kidney. The organic lead in auto exhaust from burning leaded fuel

degrades rapidly but becomes a source of inorganic lead.

Organotin compounds are used in metal coatings to prevent biological growth on ship

hulls and in cooling towers. Tributyltin is one of the common compounds used in this way.

However, it has been found to exert signiﬁcant toxic effects in estuaries after leaching

from ship hulls.

Chromium is used in leather tanning, paints, and pigments. It is found in valences from

+II to +VI, but the trivalent and hexavalent are the most important biologically. Trivalent

chromium is the most common form. It is an essential nutrient, being needed as a cofactor

for insulin. Hexavalent chromium is corrosive and causes allergic skin reactions on dermal

exposure and cancer by inhalation. The toxicity of hexavalent chromium may be caused by

reactions involving the reduction of the hexavalent to the trivalent form within cells.

Zinc is commonly used in galvanic protection of iron. The mechanism of protection

involves the oxidation of the zinc to soluble ionic forms. Zinc toxicity causes anemia

in mammals by interfering with absorption and utilization of copper and iron. The zinc

level that causes toxic effects depends strongly on the ratio of zinc to copper.

Arsenic is found as high as 5 mg/kg in seafood. Trivalent arsenite is the most toxic

form, followed by pentavalent. It combines reversibly with thiol groups in tissues and

enzymes and can substitute for phosphorus in biochem ical reactions such as oxidative

phosphorylation. Occupational exposure has been associated with lung cancer but has

not been shown to cause cancer in lab animals. Inges tion has been related to cancer of

the skin, liver, bladder, and lung. Noncarcinogenic effects range from loss of appetite

to irritation of epithel ial tissues to paralysis of the hands and feet. The U.S. drinking

water standard is 10 mg/L as of January 2006. Natural levels of arsenic as high as

280 mg/L are found in drinking waters in New Hampshire. Some 20 to 60 million people

in Bangladesh use water above 50 mg/L, some as high as 2000 mg/L. Another effect

commonly found in Bangladesh is thickening and discoloration of the skin. As a result,

victims there have been socially ostracized. Twenty to thirty years after exposure to

500 mg/L, about 10% of people develop cancer; 60 mg/L in drinking water is rapidly fatal.

Aluminum has been found to be concentrated in the brains of people with Alzheimer’s

disease (AD). However, it is not known if this is a cause or a result of the disease. There

are a number of epidemiological studies linking dementia to aluminum in drinking water.

However, other evidence contradicts this, such as the fact that studies of humans and ani-

mals exposed to large amounts of aluminum do not show development of AD. Aluminum

has also been found to cause skeletal problems in adults and infants who received large

doses as part of a medical therapy.

Beryllium causes pulmonary ﬁbrosis when inhaled, hypersensitivity reactions on

dermal contact, and is a probable human carcinogen. Inhaled nickel is an occupational

METALS 805

carcinogen. Nasal cancer predominates but also causes cancer in the lung, larynx, sto-

mach, and possibly the kidney.

Metals toxicity testing in aquatic environments can be difﬁcult, due to the sensitivity of

metals to organic complexation. The test organisms themselves can produc e such organ-

ics, possibly confounding the test. Table 21.1 shows acute toxicity data to aquatic and

marine organisms for several metals. The ranges for aquatic and marine organisms do

not differ greatly, overlapping substantially in almost every case. Acute toxicity of metals

to ﬁsh is usually associated with damage to the gills. Chronic toxicity is usually measured

using the more sensitive embryonic and larval life stages of aquatic animals. Most metals

bioaccumulate but do not biomagnify. Bioac cumulation factors range from 100 to 10

One metal that does biomagnify is mercury in the organic form. Sediments tend to

have much higher metal concentrations than the water column; thus, animals that feed

in the sediment tend to have higher body burdens. Another way to sum marize the toxicity

of metals is to rank them by toxicity for various types of organisms, as in Table 21.2.

TABLE 21.1 Acute Toxicity: 48- to 96-h LC

or EC

of Several Aquatic and Marine Phyla

Organism Cadmium Chromium Copper Mercury Lead Zinc

Arthropods 0.005–0.55 0.008–10.1 0.05–3.0 0.00002–0.040 NA 0.030–9.0

(crustaceans) 0.015–47 10 0.05–100 0.004–0.4 0.7–3.0 0.2–5.0

Freshwater insects <0.003–18. 2.0–64.0 0.007–1.2 0.28–5.5 0.04–5.5

Annelids NA NA 0.06–0.90 NA NA NA

0.1–0.5 0.01 –0.09 NA 0.8–50.

Mollusks NA NA 0.04–9.0 0.09–2.0 NA 0.5–20.

2.2–3.5 14–105 0.2–8.0 0.004–30. 0.8–30. 0.1–40.

Vertebrates NA NA 0.01–0.9 0.003–20. 1.0–500. 0.05–7.

Salmonid ﬁsh 0.03–0.5 NA NA 20.–70.

Centrachidae 12.6–126. 36.2–40. 0.7–10.0 3.0–10. 20.–400. 1.0–20.

or other ﬁsh 22–55 91 NA NA NA NA

Algae NA NA 0.001–8.0 <0.0008–2.0 0.5–1.0 0.03–8.0

Chlorophyta NA <0.005–0.4 NA 0.05–7.0

Diatoms NA NA 0.005 –0.8 NA NA NA

0.005–0.05 0.0001–0.010 NA 0.2–0.5

Results are given in mg/L. The ﬁrst set of numbers is for aquatic organisms, the second is for marine. NA, not available.

Source: Based on Connell and Miller (1984) and Rand and Petrucelli (1984).

TABLE 21.2 Ranking of Metal Toxicity for Several Groups of Organisms

Organism Ranked Sequence of Toxicity

Algae (Chlorella vulgaris)Hg> Cu > Cd > Fe > Cr > Zn > Ni > Co > Mn

Fungi Ag > Hg > Cu > Cd > Cr > Ni > Pd > Co > Zn > Fe > Ca

Plants (barley) Hg > Pb > Cu > Cd > Cr > Ni > Zn

Protozoa (Paramecium) Hg, Pb > Ag > Cu, Cd > Ni, Co > Mn > Zn

Annelida (polychaete) Hg > Cu > Zn > Pb > Cd

Vertebrates (stickleback ﬁsh) Ag > Hg > Cu > Pb > Cd > Au > Al > Zn > H >

Ni > Cr > Co > Mn

> K > Ba > Mg > Sr > Ca > Na

Mammals (rat, mouse, rabbit) Ag, Hg, Tl, Cd > Cu, Pb, Co Sn, Be, In, Ba, Mn, Zn, Ni,

Fe, Cr > Y, L a > Sr, Sc > Cs, Li, Al

Source: Connell and Miller (1984).

806 TOXICITY OF SPECIFIC SUBSTANCES

21.2 PESTICIDES

Pesticides can be classiﬁed by function and divided into subclasses by structure

(Table 21.3). However, some of the structural types are used for several functi ons. For

example, carbamates are used as both insecticides and herbicides, as is the organochlorine

hexachlorobenzene. Before the development of synthetic pesticides during World War II,

other compounds were used, such as arsenicals and nicotine. What they all have in com-

mon is that they are intended to control or eliminate undesirable organisms. The emphasis

here will be on the insecticides and herbicides because of their wider distribution in the

environment. The structures of some of these compounds are shown in Figures 21.1

and 21.2.

Organochlorine (OC) pesticides are persistent, bioaccumulate, and biomagnify. Thus,

their use is avoided now. The organophosphorus (OP) compounds do not have these char-

acteristics but are extremely toxic to mammals. The carbamates are similar to OP com-

pounds but less acutely toxic to mammals. The botanically derived compounds include

pyrethrin, which is isolated from the chrysanthemum, and permethrin, a synthetic

compound. They are effective and relatively safe. They readily degrade on exposure to

sunlight. Half-lives in soil for OCs range from 1 to 12 years; OPs from 0.2 to 0.5 year;

carbamates from 0.05 to 1.0 year.

The atmosphere is a major route of dispersion. Many pesticides are applied by

spraying. The less soluble substances tend to be distributed in the environment adsorb-

ed to particles. As a result, some are transported in signiﬁcant quantities over long

distances attached to dust particles in the atmosphere or as suspended solids in aquatic

systems.

Many pesticides are degraded by photoxidation and by microbes in the environment

into other toxic substances. DDT is converted to DDE, aldrin to dieldrin, and heptachlor

to heptachlor epoxide.

TABLE 21.3 Types of Pesticides and Some Examples

Insecticides

Organophosphorus Diazinon, dichlorvos, dimethoate, malathion, parathion

Carbamate Carbaryl (Sevin), propoxur (Baygon), Aldicarb (Temik) methiocarb

Organochlorine DDT, methoxychlor, toxaphene, mirex, Kepone (chlordecone)

Cyclodienes Aldrin, chlordane, dieldrin, endrin, endosulfan, heptachlor

Botanicals Pyrethrin, permethrin

Herbicides Chlorophenoxy acids (2,4-D, 2,4,5-T), hexachlorobenzene (HCB)

Nitrogen-based: Picloram, Atrazine, diquat, paraquat

Organophosphates: glyphosate (Roundup)

Antimicrobial Chlorine, quaternary alcohols

Fungicides Nitrogen-containing: triazines, dicarboximides, phthalimide

Wood preservatives: creosote and pentachlorophenol, hexachlorobenzene

Rodenticides Warfarin, sodium ﬂuoroacetate, strychnine

Fumigants Acrylonitrile, chloropicrin, ethylene dibromide, 1,3-dichloropropane

Phytotoxins Copper and copper compounds

Antifoulants Organic tins (low phytotoxicity): tributyltin

PESTICIDES 807