Toxicity

Hazardous Wastes Characteristics:

Reactivity
Corrosivity
Ignitability
Toxicity
- Mild allergic reactions to death

A toxic substance is a substance that can be poisonous or cause

health effects.
Some substances are more toxic than others. The toxicity of a
substance is described by the types of effects it causes and its
potency (strength).

Why should an engineer know about toxicology?

ENVE 637
Toxicokinetics (Pharmacokinetics)

Fate of Substances
To produce a toxic effect
the chemical agent or its
biotransformation products must reach the
critical site of action in a target organ at a
sufficiently high concentration and for a
sufficient length of time.
Exposure Routes
Inhalation
(breathing) of
gases, vapors, dusts
or mists
Ingestion
(swallowing) of
food, drink or other
substances
Dermal Contact
(touching) with the
skin or eyes

ENVE 637
Absorption --- It depends on the route:
Inhalation route – toxic fumes, particulate
and toxic gases may be absorbed through the
lungs.
Ingestion –GIT is the most important route of
absorption, as most acute poisoning involve
ingestions.
Dermal route – lipid solubility of a substance
is an important factor affecting the degree of
absorption through the skin

Overview of absorption, distribution, storage, transformation, and

elimination of a toxic substance in the human body.

Lead
 Airborne particulate  30-50% deposited in the
respiratory and all is absorbed over time
 Ingested  50% in children and 8 – 15% adults
 Dermal  Insignificant
Absorption ---
Administered Dose: The amount of a
particular toxic substance exposed to a body.
Although the AD is important, the amount of
the toxic chemical absorbed by the body and
the amount reaching the target organ are also
important.
Intake (target) Dose
Uptake (effective) Dose
The former is the intake and uptake dose and
the latter can be termed the target or effective
dose.
Absorption Mechanisms
 Diffusion
Most toxic agents pass through cell membranes by simple diffusion.

The rate of diffusion depends on the chemical and physical properties of a toxic agent,
particularly its degree of ionization, lipid solubility, protein binding, and water solubility.

o Lipid solubility is the most important property. It is a measure of the affinity of a chemical
substance for fat-like solvent (e.g., lipid ) versus water-like solvent (e.g., blood, urine).

o High Kow - The property of lipid solubility is indicated by an octanol/water partition coefficient
> 1 (kow the affinity for lipids

ENVE 637
 Distribution: The apparent volume into which a
substance is distributed.
- Blood stream
- The factors influence distribution are
absorption, perfusion (the movement of
blood through an organ issue), exposure
route, and tissue affinity. Toxic compounds
distribute partially and unequally to multiple
"compartments" of the body rather than
totally to one or equally to all.

 Storage - The fraction that is stored.

Important storage sites include the following
examples:
o Blood plasma for compounds bound by blood
proteins (e.g., mercuric ions)
o Bone for lead, radium, and fluoride
o Kidneys for cadmium
o Thyroid gland for iodine
On reaching an organ, a toxicant can cause three events other than
storage, as follows:
o Biotransformation (metabolism) : enzyme-rich organs, such
as the liver, metabolize the toxic substance
o Elimination: Toxic substances are not stored and, along with
most metabolites, are eliminated from the body.
o Formation of chemical: Many toxic agents attach only target
organs that have specific receptor proteins.
Biotransformation (Metabolism): The biochemical transformation of
a chemical. The body transforms a chemical and makes it more
water soluble so the chemical can be eliminated more rapidly via the
kidney into the urine.
Some substances are rendered water-soluble and transported
by blood flow to the kidneys, which filter or otherwise remove
polar toxicants and metabolites from blood and transport them
as concentrated solutes to the bladder for elimination in urine.
Some hydrophobic toxicants, or their biotransformation
products, remain concentrated in the liver.
Example: Benzene is metabolized primarily in the liver where
much of it, is oxidized to benzene oxide

 Benzene oxide is unstable and is hydroxylated to phenolic

compounds, which are excreted in urine together with
other metabolites. Analyses of specific metabolites in the
urine are frequently used as quantitative indicators of
exposure to substances. This is termed biological
monitoring and the metabolite is a biomarker. Phenol is
thus a biomarker for benzene exposure.
 Biotransformation does not necessarily reduce the toxicity
of a substance. On the contrary, some metabolites are
many times more toxic than the parent compound.
 For example, benzene must undergo metabolic
transformation to produce its toxic effects in bone marrow.
 As another example, benzo(a)pyrene, a substance in
tobacco smoke, is noncarcinogenic; however, it is
biotransformed to its diol epoxide which is a potent
carcinogen.
 Other examples of such a toxic transfonnation are the https://ehp.niehs.nih.gov/wp-
conversion of parathion to paraoxon and of the pesticide content/uploads/100/ehp.93100293.pdf
DDT to DDE (responsible for eggshell thinning).

ENVE 637
Excretion is the final means of chemical
elimination, either as metabolites or unchanged
parent chemical.
Excretion through the lungs is the major route for
gaseous substances; and
in the case of non-volatile water – soluble
substances, the kidneys are the most important
routes of excretion.
Additional routes include sweat, saliva, tears, nasal
secretions, milk, bile and feces.
Example

• Metabolism of ethanol is a zero-order reaction (i.e. elimination is constant regardless of

concentration). If an average human is able to metabolize 10 ml of ethanol per hour, how long a
time is required to eliminate a six (6) pack of Sculpin?

ENVE 637
EXAMPLE. CALCULATION OF THE HALF-LIFE FOR ELIMINATION OF METHYL MERCURY FROM THE
HUMAN BODY. Many metabolic processes follow first-order kinetics (i.e., the formation or
elimination of a substance depends on the absorbed concentration) and the level of the substance
changes by some fraction per unit time, the first-order rate constant k. The time required for the
concentration to decrease by one-half is known as the half-life (t1/2). The half-life of a chemical
obeying first-order kinetics is constant and independent of administered dose.
From determination of the levels of methyl mercury in an individual surviving poisoning by a
fungicide in Iraq, the average excretion rate was found to be 1.75 % of the total body burden per
day. What value for the half-life can be determined on the basis of these observations?

ENVE 637
Solution

ENVE 637
 Exposure Period

Assuming first-order elimination kinetic , the "average' body burden at steady

state (XØ ) after repeated exposure:
Acute : 1 Day
Subacute : 10 Days
Sub-chronic : 2 Weeks – 7 years
Chronic : 7 years - Lifetime

ENVE 637
 When an acute toxic dose is fractionated into smaller portions and administered over a longer period of time,
the toxic effect usually decreases.
 Figure 5-5 illustrates the case of repeated exposure to a compound at two different administered doses neither
dose being sufficiently high to cause a toxic effect after a single exposure. The interval between exposures is the
same for both doses. If the elimination rate allows the toxic chemical to decline to pre-exposure levels as in the
case of the lower doses it prevents the total body burden from reaching the toxicity threshold. However, if the
elimination rate cannot keep pace with uptake, as in the case of the higher exposure, this toxicity threshold is
eventually reached.
 Classifications of Toxic Actions and Effects
• Classification by end point: carcinogenic effects with tumor induction as the end point and
noncarcinogenic effects including all other effects.

The end point should be clear, definitive and

directly measurable such a death or organ
dysfunction. Having to use an equivocal end
point, such as retardation of mental
development, makes the interpretation of the
results more susceptible to question.

ENVE 637
 Classifications of Toxic Actions and Effects
• Classification by end point: carcinogenic effects with tumor induction as the end point and
noncarcinogenic effects including all other effects.

ENVE 637
Endocrine disruptors
 has captured the attention of regulatory agencies
in recent years,
 also known as "hormonally active agents" (HAAs),
 include chemicals such as the polychlorinated
biphenyls (PCBs), 1,1 -dichloro-2,2-bis (p-
chlorophenyl)ethene (DDE), methoxychlor, dibutyl
phthalate, pesticides and dioxin (found in meat).
 These compounds are suspected to mimic or
modulate the action of naturally occurring
reproductive and thyroid hormones.
 Because of their hormonal nature, these
substances have demonstrated a wide range of
effects in humans, laboratory animals, and
wildlife, including reproductive, immunological,
neurological, and developmental effects.
 Classifications of Toxic Actions and Effects
Classification by target organ: In some cases, a specific target organ, or tissue,
may be distinguished and used as a basis for classification (e.g., the kidney in case
of cadmium toxicity, the bone marrow for benzene, the brain for methyl mercury,
the liver for carbon tetrachloride, the lung for the pesticide paraquat, the eye for
the antimalarial drug chloroquine).

Toxicological effects may also be characterized in the following manner:

 Immediate versus delayed effects
 Irreversible versus reversible effects
 Local versus systemic effects
Classification by immediate versus delayed effects: The ingestion of a lethal dose of a soluble
cyanide results in death within a few minutes (immediate toxicological action/Acute). In
contrast, carcinogenic agents induce tumors in humans only after a latency period possibly
extending 10 to 30 years (Chronic).

ENVE 637
• Classification by irreversible versus reversible effects: The beneficial pharmacological action of
drugs is usually reversible. Skin and liver have a high repair capacity; therefore, moderate damage
induced at these sites is often reversible. Injuries of the central nervous system caused by
chemicals are, on the other hand, mostly irreversible because of the slow or nonexisting
regenerative power of these tissues.

• Classification by local versus systemic effects: A distinction is made between local toxic effects
and systematic action. Reactive chemicals such as acid anhydrides, epoxides, strong acids and
bases, acyl chlorides and corrosive agents cause toxic effects, such as cell necrosis, immediately
on coming into contact with tissue (e.g., skin and eyes, mucous membranes of the respiratory
tract). In contrast, systemic poisons may exert their toxic action at a point distant from the site of
absorption (e.g., tri-o-cresyl phosphate), which induces damage to the peripheral nervous system
on ingestion of small amounts over extended periods of time.

ENVE 637
• All chemicals can be hazardous in large enough quantities.
• Chemical hazards can cause cancer, birth defects and improper functioning of the human body. Common groups of
hazardous chemicals, include carcinogens, chemical mutagens, teratogens, neurotoxins, allergens and endocrine
disruptors.
 Dose – Response

A number of factors influence the degree of toxic action. The dose represents the major
determinant of the extent of toxic action. It also depends on the vulnerability of the exposed
individual.
The vulnerability of an individual: age, sex, diet, health status, genetics, prior exposures to the
agent and exposures to other agents.
Dose-response assessment involves describing the quantitative relationship between the amount
of exposure to a chemical and the extent of toxic injury or disease. The description is different for
non-carcinogenic versus carcinogenic effects.

https://www.epa.gov/sites/production/files/2014-12/documents/rfd-final.pdf

ENVE 637
 Figure 5-11: Dose-response relationship
• LD50 Lethal dose to 50% of test organisms (dose-versus mortality)
 In humans, lead causes anemia by
inhibiting the synthesis of
hemoglobin from various
precursors.
 This results in the accumulation
of the precursor protoporphyrin
in the erythrocytes (red blood
cells).
 Thus, erythrocyte protoporphyrin
in blood can be used as a
biomarker for measurement of
the "toxic" action of lead and has
been found to constitute a
sensitive and reliable indicator of
low-level exposure to lead.
• www.Flintwaterstudy.org
• 90th percentile Lead : 25.2 ppb in
water
• EPA standard: 15 ppb
• 38 µg/dL  highest observed in
blood

ENVE 637
Figure 5-14:
Health
effects from
breathing
and/or
ingesting
lead.

ENVE 637
Figure 5-15: Health
effects from
breathing benzene.

ENVE 637
LD50 :Median lethal dose. This is the dose, usually expressed as
milligrams per kilogram body weight, at which only 50% of the
organisms remained alive.

LC50 :The equivalent for inhaled substances is the median lethal

concentration, where the dose is expressed as the
concentration of the substance present in a volume of inhaled
air.
 Noncarcinogens
• Threshold
• NOAEL
• ADI
• RfD

ENVE 637
 Noncarcinogens
• Threshold
• NOAEL
• ADI
• RfD

ENVE 637
 Noncarcinogens

Dose response curve, LOAEL and NOAEL

ENVE 637
Noncarcinogens

ENVE 637
Noncarcinogens

ENVE 637
 Noncarcinogens

Acceptable Daily Intake (ADI): the level of daily intake

 Threshold of particular substance should not produce an adverse
 NOAEL health effect.
 ADI
 RfD

ENVE 637
 Noncarcinogens

 Threshold
 NOAEL
 ADI
 RfD

ENVE 637
 Noncarcinogens

 Threshold Reference Dose (RfD):

 NOAEL
 ADI
 RfD

ENVE 637
 Noncarcinogens

𝑵𝑶𝑨𝑬𝑳
𝑹𝒇𝑫 (𝒐𝒓 𝑨𝑫𝑰) =
𝑼𝑭𝑯 𝒙 𝑼𝑭𝑺 𝒙 𝑼𝑭𝑳 𝒙 𝑼𝑭𝑪 𝒙 𝑴𝑭

Animal to Human (10H) (UFH)

 Animals of higher body weight appear
more sensitive per mg/kg than
smaller animals
 By this calculation, a human is about
6 times more sensitive than a rat, 4
times more sensitive than a guinea
pig and 12 times more sensitive than
a mouse
 Therefore, factor of 10 is
overestimate for some species,
underestimate of sensitivity
differences for others ENVE 637
 Noncarcinogens

Average to Sensitive Human (10S) (UFS)

ENVE 637
 Noncarcinogens
LOAEL to NOAEL (10L) (UFL) Data Quality (MF 1-10)

𝑵𝑶𝑨𝑬𝑳
 𝑹𝒇𝑫 (𝒐𝒓 𝑨𝑫𝑰) =
𝑼𝑭𝑯 𝒙 𝑼𝑭𝑺 𝒙 𝑼𝑭𝑳 𝒙 𝑼𝑭𝑪 𝒙 𝑴𝑭

ENVE 637
 Noncarcinogens

𝑵𝑶𝑨𝑬𝑳
𝑹𝒇𝑫 (𝒐𝒓 𝑨𝑫𝑰) =
𝑼𝑭𝑯 𝒙 𝑼𝑭𝑺 𝒙 𝑼𝑭𝑳 𝒙 𝑼𝑭𝑪 𝒙 𝑴𝑭

ENVE 637
 Noncarcinogens

𝑵𝑶𝑨𝑬𝑳
𝑹𝒇𝑫 (𝒐𝒓 𝑨𝑫𝑰) =
𝑼𝑭𝑯 𝒙 𝑼𝑭𝑺 𝒙 𝑼𝑭𝑳 𝒙 𝑼𝑭𝑪 𝒙 𝑴𝑭
ENVE 637
 Example
In a subchronic oral toxicity study in mice, a lowest observed adverse effect level (LOAEL) of 5
mg/kg.day was determined for a specific agent. The quantity of the data is given a high rating by the
expert evaluating the data. What is the RfD?

𝑵𝑶𝑨𝑬𝑳
𝑹𝒇𝑫 (𝒐𝒓 𝑨𝑫𝑰) =
𝑼𝑭𝑯 𝒙 𝑼𝑭𝑺 𝒙 𝑼𝑭𝑳 𝒙 𝑼𝑭𝑪 𝒙 𝑴𝑭

ENVE 637
 Example
In a subchronic oral toxicity study in mice, a lowest observed adverse effect level (LOAEL) of 5
mg/kg.day was determined for a specific agent. The quantity of the data is given a high rating by the
expert evaluating the data. What is the RfD?
𝑵𝑶𝑨𝑬𝑳
𝑹𝒇𝑫 (𝒐𝒓 𝑨𝑫𝑰) =
𝑼𝑭𝑯 𝒙 𝑼𝑭𝑺 𝒙 𝑼𝑭𝑳 𝒙 𝑼𝑭𝑪 𝒙 𝑴𝑭

ENVE 637
 Noncarcinogens
Calculation Procedure for Assessment of Noncarcinogenic Risk

The preliminary assessment of nancarcinogenic risk of a hazardous waste site as

recommended by the EPA is typically calculated in four major steps:
1.) Identify discrete exposure conditions:
 Exposure route
 Frequency
 Duration
 Administered dose
2.) Derive appropriate RfD for each discrete set of conditions.
3.) Evaluate hazard for nancarcinogenetic effects as a ratio of exposure dose to
the recommended RfD.
4.) Aggregate hazard for multiple chemical agents and exposure pathways as a
hazard index, where appropriate.

ENVE 637
Example

Example 5-5. The use of RfDS to evaluate noncarcinogenic hazard.

Because of contamination from hazardous waste originating from a metal plating facility, the water from a nearby
community water supply well contained cyanide at a concentration of 30 µg/L, nickel at 120 µg/L, and chromium (III)
at 12,400 µg/L. The daily water intake is assumed to be 2 L, and the body weight of an adult human 70 kg. Do these
exposures indicate an unacceptable hazard?

ENVE 637
Example
Example 5-5. The use of RfDS to evaluate noncarcinogenic hazard.
Because of contamination from hazardous waste originating from a metal plating facility, the water from a nearby
community water supply well contained cyanide at a concentration of 30 µg/L, nickel at 120 µg/L, and chromium (III)
at 12,400 µg/L. The daily water intake is assumed to be 2 L, and the body weight of an adult human 70 kg. Do these
exposures indicate an unacceptable hazard?

ENVE 637
Example

ENVE 637
Example

https://www.epa.gov/expobox/exposure-assessment-tools-routes-ingestion
ENVE 637
Example

ENVE 637
Example

ENVE 637
Example

ENVE 637
Example

ENVE 637
Example
Arsenic at 270 µg/L has been discovered in a spring serving a a) What is the lifetime cancer risk from
rural community with a population of 5000. The spring feeds a arsenic in the drinking water for an adult
small creek that provides the community with a trout fishery. living in the exposed community?
The community has used the spring as a drinking water source
for 12 yr, but it is unknown how long the contamination has b) What is the lifetime cancer risk for adult
existed. The toxicology of arsenic is characterized by the residents exposed to arsenic through
following parameters: inhalation, if the exposure duration is 30 min
oral route potency factor (PF) 1.75 (mg/kg.d)-1 daily and the concentration is 0.13 µg/m3?
inhalation route potency (PF) 50 (mg/kg.d)-1 0.0003
reference dose (RfD) mg/kg.d The chronic daily intake, CDI:
bioconcentration factor (BCF) 44 L/kg
𝐶( 𝐷𝐼 %𝐴 )( 𝐸𝐷 %𝑇 )
The exposure factors representing the community are 𝐶𝐷𝐼 =
(𝐵𝑊)(𝐿𝑇)
ingestion ( drinking water) ……… 2 L/d (adult)
C: Concentration (mg/L)
1 L/d (child)
ingestion (fish) ………………………… 54 g/d DI: Daily intake (L/d)
inhalation ………………………………… 20 m3 /d (adult) ED: Exposed duration (yr)
BW: Body weight (kg)
12 m3/d (child)
lifespan ................... 70 yr LT: Lifetime (yr)
body mass............... 70 kg (adult) %A: percent absorbed (%)
%T: percent of time exposed (%) ENVE 637
15 kg ( child)
Example

ENVE 637
Permissible Daily Exposure (PDE)
 Carcinogens

How do we know which chemical substances are carcinogenic and how potent they are?

 Are there sufficient human epidemiologic data, mainly from studies of works?

 EPA’s Group A – Human Carcinogens: Compounds for which

“there is sufficient evidence to the agent and cancer.”
Potential Human Carcinogens
 Several hundred substances
 Animal testing, usually rats and mice
 >800 hazardous substances regulated
under CERCLA
 EPA has identified 160 substances as
“potential carcinogens or as substances having
carcinogenic potential.”

ENVE 637
 Carcinogens
https://www.epa.gov/sites/production/files/2014-05/documents/table1.pdf

ENVE 637
 Carcinogens

The assessment of human cancer risk based

on animal tests requires two major
considerations:
1. Is the tested chemical a carcinogen?
2. How are data from experimental animals
applied to human?
To predict the likely outcome from
human exposure to carcinogenic chemicals
requires the development of dose-response
relationships. To develop these relationships,
toxicologists ordinarily depend on animal data.

ENVE 637
 Carcinogens

The dose-response curve is asymptotic to "zero“, since there is no threshold, no safe level. The public has ex-
pressed concern with any level, and regulatory agencies tend to establish a regulatory goal of 1 in 1 million (1 x
10-6 or 0.0001 percent) excess lifetime cancer risk.

Example:
For dose-response relationship shown in Figure 5-23, what is
the minimum dose tested? What is the mean incidence
induced by this dose? How does this compare with the 10-6
goal?

Solution. The minimum dose tested is 2.0 mg/(kg · day),

yielding a mean excess tumor incidence of about 10 percent.
This incidence is 100,000 times (0.10/0.000001=100,000)
greater than the 10-6 goal.

ENVE 637
 Carcinogens

The calculation of carcinogenic risk involves the use of a slope factor (SF). An SF is basically the slope of the
dose-response curve at very low exposures and was formerly referred to as the carcinogen potency factor (CPF).

Assume: No threshold and linear

ENVE 637
Carcinogens

https://www3.epa.gov/hudson/tables.htm

ENVE 637
 Carcinogens

EXAMPLE 5-7. US E OF SLOPE FACTORS. What are the maximal

number of excess lifetime cancer cases expected for a
population of 100,000 adults with a daily intake of
0 .14 mg of benzene?
exposure factor (EF) : 1
Solution
1. The slope factor for benzene is 0.029 [mg/(kg · day)]-1
2. Assuming an adult weight of 70 kg, the lifetime cancer risk is calculated as:
𝑚𝑔
0.14 𝑥 1 𝑥 0.029
𝑘𝑔
𝐼𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙 𝑐𝑎𝑛𝑐𝑒𝑟 𝑟𝑖𝑠𝑘 = = 0.000052 or 0.0052%
70 𝑘𝑔.𝑚𝑔 /(𝑘𝑔.𝑑𝑎𝑦)
Maximal cases = risk x exposed population
= 0.000052 X 100,000 = 5 excess lifetime cancer cases

ENVE 637
 Carcinogens

The dose-response assessment step : is to define the relationship between the dose of an agent and the
likelihood of a carcinogenic effect. Numerical estimates of risk can be presented in one or more of the
following four ways: (1) unit risk; (2) the concentration corresponding to a given level of risk; (3) individual
risk; and (4) population risk.

The Integrated Risk Information System (IRIS) chemical files include only unit risks and risk-related
air and water concentrations.

Dose-response assessment includes

(1) selection of the appropriate data sets to use;
(2) derivation of estimates at low doses from experimental data at high doses, using an extrapolation model; and
(3) choice of an equivalent human dose when animal data sets are used.

https://www.epa.gov/iris/epas-approach-assessing-risks-associated-chronic-exposure-carcinogens

ENVE 637
 Carcinogens
EXAMPLE. EXCESS CANCER CASES.
Arsenic has a 5x I0-5 (ug/L)-1 drinking water unit risk. The excess
cancer cases due to arsenic in drinking water predicted for one
million people drinking water with an arsenic concentration of
2 ppb all of their lives is most nearly?

Solution
The drinking water unit risk multiplied by the concentration in water multiplied
by the number of exposed people is the number of predicted excess cancer
cases.
Excess cancer cases = (C ) x ( unit risk) x ( exposed population)

ENVE 637
 Carcinogens
Mixed exposure to carcinogens

Is government’s approach (EPA’s linear-dose response model) too overprotective or underprotective?

 Only one compound (model) is tested on animals

 Human population receive more than one carcinogenic substance exposure in environment
Simplified risk assessment methodology – for dealing with mixed exposure to carcinogens (additive model)
 Overall carcinogenic risk is equivalent to the sum of individual risks of each substance.

If the relative risk for lung cancer from tobacco smoking is 10 and
the relative lung cancer risk from asbestos exposure is also 10, the
classic additive model would conclude that the lung cancer risk
from exposure to both tobacco smoke and asbestos would be 20.
However, it has been found that the lung cancer risk among
asbestos workers who smoked was nearly 100 times that of
workers in other industries who did not smoke. Carcinogenic
synergism : 10x10=100 not (10+10=20)

ENVE 637
 Ecotoxicology
o A relatively young scientific discipline
o Addresses effects on groups of populations interacting with the physical environment
o It is important to understand how the chemical interacts with the organisms in the environment (e.g.
physical alteration of habitat by chemical spill; loss of a food source, biological or chemical degradation).
o Ex. An accidental oil spill can produce a variety of effects including reduction of photosynthesis from
decreased light penetration, lethality to aquatic organism from exposure to lighter aromatic hydrocarbon,
and the transfer of heavier hydrocarbons through the food chain from accumulation in tissue.
o exposure, absorption, metabolism, and manifestation are also used for ecotoxicology.

ENVE 637
 Ecotoxicology
Toxic End Point : should be evaluated for the selection and design of an appropriate test method.
1.) Assessment end points: are ecological characteristics – indicate a need for mitigative action. 2.) Mea-
surement end point: provides a quantitative expression (i.e. a measurable characteristic)

ENVE 637
 Ecotoxicology
Bioassay
o To evaluate the hazards associated with chemical exposure of nonhumans, ecotoxicologists have historically
relied on the combination of short-term and long-term bioassays.
o A technique to measure effects of chemical exposure.
o Results from short- and long-term toxicity tests are often used to establish water
o Quality criteria, to estimate the killing or knock-down power of pesticides, to calculate
o percent limitations for effluent discharge, and to project the potential impacts of catastrophic spills and
chemical accidents, and the actual and potential effects of hazardous waste disposal and cleanup.
Short-term toxicity tests, often referred to as acute toxicity tests, are used to evaluate
severe effects from exposures spanning relatively short periods of time.
o most often used to evaluate percent affected by a chemical compound.
o to predict potential human toxicity, the LD50 is used as an empirical estimate of the
dose associated with a 50 percent lethal response in the test population.
o LC50 is used to measure lethality via inhalation or exposure in an aqueous solution
o The standard test for measuring acute lethality is designed to produce a 50% lethal
response in a test organism after a 96-hour exposure duration. While responses for
shorter exposure durations are often cited, the 96-hour LC50 is recognized as the
standard.
ENVE 637
Ecotoxicology

ENVE 637
Ecotoxicology

Acute toxicity tests can be designed to answer

numerous questions about waste management
such as the toxicity of an individual chemical,
mixture of chemicals, leachate, or other
concentrated waste streams. Also, tests can be
used to locate toxic "hot spots” at waste sites,
and to evaluate the effectiveness of waste
treatment technologies.

ENVE 637
Ecotoxicology

ENVE 637
 Ecotoxicology
EXAMPLE. ANALYSIS OF TOXICITY DATA. EXCESS CANCER
CASES.
Using the following hypothetical data determine the 48 and 96-
hour LC50 values in percent by volume.

ENVE 637
 Ecotoxicology

Solution.
1.) Plot the concentration of wastewater in percent by volume
(log scale) against test animals surviving in percent (probability
scale).
2.) Fit a line to the data points by eye, giving most
consideration to the points lying between 16 and 84 percent
mortality.
3.) Find the wastewater concentration causing 50 percent
mortality. The estimated LC50 values are 16.5 percent for 48 h
and 6.5 percent for 96 h.

ENVE 637
 Ecotoxicology

Long-term toxicity tests, commonly referred to as chronic toxicity tests, are used to evaluate whether extended
laboratory exposure of different life stages ( e.g., embryos, juveniles and adults) to a constituent will adversely
affect individuals, species, or populations.

Such benchmark concentrations include the lowest observed effect level (LOEL), which represent the lowest
concentration associated a with a measurable effect, and the no observed effect level (NOEL), which denotes a
concentration that did not produce a measurable effect.

Chronic toxicity usually provide a more sensitive measurement of toxicity.

To develop acceptable exposure concentrations (e.g., water quality standards), ecotoxicologists use a
subcategory of chrome toxicity tests referred to as life-cycle tests. The specific tests evaluate the responses of
individuals from species over a complete Iife-cycle to evaluate effects on survival growth, and reproduction.

The problems associated with chronic toxicity tests are the time and costs for conducting such tests.

ENVE 637
 Ecotoxicology

EXAMPLE 5-8. PREDICTING BIOCONCENTRATION. Routine monitoring of sediments and surface water
downstream from a hazardous waste site indicate that reportable concentrations of the pesticide DDT are
present. On the average, sediments and surface water contain 33 mg/kg and 0.25 µg/L, respectively.
Considering that the U.S. Food and Drug Administration has identified levels of 5 ppm or higher of DDT as
requiring action, is there a reason to be concerned about potential accumulation of DDT in fish
tissue near this site?

ENVE 637
 Ecotoxicology
Solution: Since the routine monitoring does not provide
information regarding DDT residues in fish tissue, we
refer to Table 5-15 and bioconcentration factor (BCF).
Transforming the log BCF of 4.73, we estimate a BCF of
54,000 (mg/kg DDT) in tissue per mg/L DDT in water, or
L/kg).
[log(54,000)=4.73]
Substituting our monitoring data and the
empirical BCF for DDT in Equation 5-4 gives

We estimate a DDT tissue residue of ~15 mg/kg. On the

basis of this estimate, it is probable that DDT residues
in tissue are an issue that should be evaluated.

ENVE 637
 Ecotoxicology

A chemical that bioaccumulates

and/or bioconcentrates can increase
in tissue concentration as the
chemical is transferred up through
trophic levels in the food chain in a
process known as biomagnification.

ENVE 637
 Ecotoxicology
Aquatic Toxicity of Trace Metals
o Trace metals naturally cycle through and
between the lithosphere, atmosphere, and
hydrosphere.
o Sources are: volcanic emissions, from
anthropogenic sources such as industrial
effluent, or nonpoint sources such as urban
storm runoff and atmospheric washout of
particulate or gaseous emissions.
o Mining, fossil fuel combustion, plating, etc.
enriched the levels of trace metals in the
environment.
o Many trace metals are essential
micronutrients for the maintenance of
aquatic life, and toxic only when exceed
nutritional requirements.

ENVE 637
 Ecotoxicology
Aquatic Toxicity of Hydrocarbons-- naturally present and resulting from anthropogenic releases
two principal subgroups: aliphatic aromatic and aromatic hydrocarbons.

EXAMPLE 5-9. PATTERNS IN

AQUATIC TOXICITY FOR ORGANIC
COMPOUNDS. A chemical
manufacturing facility produces
chlorinated benzenes. As part of
their effluent monitoring program
they conduct acute toxicity tests.
Assuming the toxicity data
presented in Table 5-19 are
representative of the results for
their toxicity testing, can you
identify a pattern relative to the
toxicity of these chlorinated
benzenes?

ENVE 637
 Ecotoxicology

Acute toxicity of chlorinated benzenes increases as the chlorine content increases.

Acute toxicity increases as the degree of halogen substitution increases.

ENVE 637
 Ecotoxicology
Aquatic Toxicity of Pesticides

o are chemical compounds capable of affecting

all types of biota, including nontarget species, to
varying degrees, depending on physiological
and ecological factors.
o many pesticide compounds are resistant to
degradation to enhance their persistence and
effectiveness.
o pesticides are usually applied in bulk quantity
and dispersed over large areas, which results in
atmospheric transport to natural systems and
runoff contamination of receiving surface water
bodies.

ENVE 637
Ecotoxicology

ENVE 637
 Ecotoxicology

EXAMPLE 5-10. ECOTOXICOLOGY OF ZINC.

Downstream of a metal-plating lagoon holding
wastewater and sludge, surface water monitoring
data indicate 4-day and 1-hour average zinc
concentrations of 14.2 µg/L and 27 µg/L. An
average water hardness value of 100 mg/L CaCO3
was also measured for the stream. For the
measured concentrations for zinc and water
hardness, and the water quality criteria for zinc, is
there reason to be concerned regarding the long-
term protection of aquatic life?

ENVE 637
 Ecotoxicology
Solution. From Table 5-22 the equation to
estimate the zinc criterion for long-term
(chronic) protection of aquatic life is as follows:

Substituting the measured hardness value

of 100 mg/L CaCO3, we estimate that the
criterion for the 4-day average zinc
concentration is:

ENVE 637
 Noncarcinogens

EXAMPLE. A chronic oral toxicity study was conducted to determine the effects of copper cyanide (CuCN) on
rats. The quality of the data is judged by the toxicologist to be “average”. The following results were obtained
from the study.

In the absence of other, more reliable published information,

what should be used as the reference dose (RfD) for human
exposure from drinking water containing copper cyanide
(CuCN)?

ENVE 637
 Noncarcinogens

Solution
uncertainty factors 10A, 10H, and 10A apply. Therefore, UF = (10)(10)(10) = 1000

Select an average modifying factor of MF = 5

ENVE 637
 Noncarcinogens

EXAMPLE. A community water supply well was found to be

contaminated with copper cyanide (CuCN), methanol (CH3OH),
and potassium cyanide (KCN). The concentrations in the water
and the EPA reference doses are as follows.

Is a 70 kg person who drinks 2 L of water daily exceeding the

safe human dose for these noncarcinogens?

ENVE 637
Noncarcinogens

ENVE 637
 Carcinogens
EXAMPLE.
A village with a stable population of 50,000 has a water supply that has been contaminated with benzene
(C6H6) from a leaking underground storage tank. The leak occurred during the 20 yr before it was removed.
The estimated average concentration of benzene during this period of leaking was 50 µg/L. It is expected that it
will take another 10 yr before the benzene will be below detectable levels. The average estimated concen-
tration of benzene during this period is 20 µg/L. The slope factor for benzene by the oral route is 2.0x 10-2
(mg/kg·day)-1. Assume a 70 yr lifespan, 70 kg adults, 10 kg children, 2 L/day adult water consumption, 1 L/day
child water consumption, and 10% children in the village. If the acceptable risks of additional cancer deaths
due to benzene in the water are 1 adult and 0.5 child, can the water supply be used for the next 10 yr or
should the village abandon the supply?

ENVE 637
Carcinogens

ENVE 637
 Carcinogens
Solution:
step 1: Find the chronic daily intake (CDI) for adults and children for each time period. Given a
total lifespan (AT) of 70 yr and an exposure factor (EF) of 1:

Step 2: Find the probable risk of additional cancers, R, for adults and children for each time period. Given a
slope factor (SF) for orally ingested benzene of 2.0 x 10-2 (mg/kg·day)-1,

R = (SF)(CDI)

ENVE 637
 Carcinogens

Step 3: Find the total excess cancers (EC) for adults and
children for each time period.

EC= (EP)(R)

The total adult excess cancer risk is

= 0.0734 + 0.367 = 0.440

Similarly, the total children excess cancer risk is given by

= 0.0286 + 0.143 = 0.172

ENVE 637
 Carcinogens
EXAMPLE. BCF. The town of Central has a water supply from
the Middle River that was discovered to be contaminated with
0.03 µg/L of heptachlor (carcinogen class B2) for 5 yr. People in
the town have continually enjoyed the large trout from the
Middle River and consume twice the EPA standard factor for
fish consumption. The slope factor for heptachlor is 4.5
(mg/kg·d)-1. What is the risk of excess cancer over the lifetime
of an adult if the heptachlor contamination is removed this
year?

ENVE 637
Carcinogens

ENVE 637
 Carcinogens
Solution Determine the standard factors.

fish consumption= (6.5 g/day)(2) = 13 g/day

CR= 2 L/day
ED= 5 yr
BW = 70 kg
BCF = 15 700 L/kg
exposure factor (EF) of 1

Calculate the CDI for heptachlor in water.

the chronic daily intake (CDI)

ENVE 637
 Carcinogens
Calculate the concentration of heptachlor in fish and determine
its CDI.

ENVE 637
 Feb 20
Hmw 3 due
Hmw 4 presentations
(please share the toxic substance you choose with others
so you don’t get the same substance)

Feb 20-22
Management Practices

Feb 27
Midterm Exam -1

ENVE 637