toxo model cram Flashcards
Toxicant:
ii. Toxin:
Toxicant: man made poison introduced into the environment
ii. Toxin: natural poison produced by a living organism
Toxicity
. Toxicosis:
Toxicity: the amount or degree of toxin/toxicity it takes to damage an
organism
iv. Toxicosis: disease state induced by the toxin/toxicant
Toxicology
Nanotoxicology
Toxicology: the branch of science which studies nature, effects, and
detection of poisons
vi. Nanotoxicology: Branch of toxicology which studies the toxicity of
nanoparticles (ultrafine particle between 1-100 nanometres in diameter)
dose/response:
dose/response: any increase in dose will cause a graded increase in
response
1. There are two types of dose-response curves
a. one that describes the graded responses of an individual
to varying doses of the chemical
b. one that describes the distribution of responses to
different doses in a population of individuals
NOAEL:
LOAEL
NOAEL: No observed adverse effect level
iii. LOAEL: Lowest observed adverse effect level
LC50:
LD50:
LC50: Lethal Concentration 50- concentration required to kill 50% of the
population
v. LD50: Lethal dose 50- dose at which 50% of population dies
Acute toxicology
Acute toxicology
- Adverse effects of a substance from an exposure for <24hrs
a. Sub-acute=> 24 hours- 1 month
Chronic toxicology
Chronic toxicology
a. Adverse effects of a substance from an exposure for >3
months
1. Sub chronic= >1-3 months
toxic endpoint
A toxic endpoint is the result of a study conducted to determine how
dangerous a substance is. The data collected from such studies are used
to report the relative toxicity of the compound to various regulatory
agencies and environmental compliance groups. Toxic endpoints can
include mortality, behavior, reproductive status or physiological and
biochemical changes.
Developmental toxicity
Developmental toxicity focuses on pre-natal development of the
embryo or fetus. Toxicity may manifest as death of the embryo or
fetus, abnormal development or birth defects or retardation of
normal growth patterns
Reproductive toxicity
Reproductive toxicity looks at all aspects of fertility. This includes
the reproductive cycle, sexual behavior, gamete (sperm or egg)
production and transport, fertility (including sperm quality and
quantity), pregnancy outcomes, gestation, childbirth, lactation and
maternal behavior. These studies also examine postnatal survival,
growth and development of offspring. Some studies look at
multiple generations to detect heritable effects.
DART studies (developmental and repro studies)
DART studies are conducted to ensure the safety of new life-saving drugs
before they go on the market. They are also used to determine the safety
of pesticides and other household or industrial chemicals. Results of
these studies are used to develop safety guidelines to reduce exposure
risks for different populations, including pregnant women, infants and
young children.
ii. Different types of studies are used to evaluate different aspects of
reproduction and development. Generally, DART studies can be divided
into two types, which can sometimes be combined. (developmental and reproductive)
Regulatory Requirements for DART Studies
Regulatory Requirements for DART Studies
1. In the U.S., the Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) have established guidelines for DART studies required for product registration and
approval. Similar regulations are in place in the European Union
(EU) and many other regions around the world. Companies must
present data from DART studies conducted per applicable
regulatory guidelines in order to market and use their products in
these countries.
Pharmaceuticals, DART studies reg requirements
Pharmaceuticals: In the U.S., the FDA approves pharmaceuticals
before they can be marketed. The toxicity tests that are required in
the U.S. are dictated by test guidelines put forth by the
International Conference on Harmonization (ICH).
Three DART tests are required for small molecule pharmaceuticals:
Three DART tests are required for small molecule pharmaceuticals:
Embryo-Fetal Development (EFD),
Fertility and Early Embryonic Development (FEED) and a Pre- and Postnatal Development study (PPN). Combination studies may be performed to reduce the number of animals needed and to obtain results more quickly. (This should be
decided on a case-by-case basis, as it may not be appropriate for a given drug.) For large molecule biopharmaceuticals, such as vaccines and
proteins, other laboratory animal species and study designs may be used.
Pesticides and Industrial Chemicals:
DART testing
Pesticides and Industrial Chemicals: Pesticides and industrial chemicals must also undergo DART testing to detect toxicity to the reproductive
system, including prenatal and postnatal development of the offspring. In the U.S., the EPA requires DART testing for product registration of
pesticides . For industrial chemicals, testing requirements are regulated by
the EPA’s Toxic Substance Control Act (TSCA). The EU has similar DART testing requirements for registration of pesticides and industrial
chemicals, which are described in the test guidelines put forth by the Organization for Economic Cooperation and Development (OECD).
Required DART studies depend on the chemical substance and its intended use and may include developmental toxicity, one- and two-generation reproductive toxicity studies, the extended one-generation reproduction study or reproductive screening tests.
Target site resistance
Target site
1. Historically, the type of resistance that farmers and researchers deal with most often is target-site resistance. Every herbicide has a specific target site in a plant. The herbicide has to bind to that
target site and effectively shut it down in order to kill the weed.
Resistance can occur when changes in the target site stop the herbicide from effectively binding there. One change to the amino acid residue chain in the protein sequence, and all of the sudden you have resistance.”
Target-site mutations are often prompted by repeated applications of the same herbicide site of action. Today, target-site resistance remains the most common type of herbicide resistance seen around the world, encompassing resistance to ALS inhibitors,
ACCase inhibitors and more.
Non-Target-Site resistance
Non-Target-Site
1. On the other end of the spectrum, non-target-site resistance, or metabolic resistance, involves more change in the plant than just at the target site alone. In this type of resistance, weeds develop
the ability to rapidly metabolize, or break down, the herbicide before it can cause significant biotoxic effects to the weed. Once an herbicide is inside a plant, it’s going to try and control it,” says
Hager. “With metabolic resistance, the weed is now behaving like the resistant crop and can rapidly metabolize the herbicide and survive.”
2. Though less common than target-site resistance, metabolic resistance is a concern on the rise.
Mixed associations
Mixed associations
- But whether you’re dealing with target-site resistance or non-target-site resistance, the control method remains the same: tank-mixing multiple herbicide modes of action in each application.
- The probability that a weed will be resistant to two different herbicides combined is less than the probability of the weed being resistant to each herbicide individually.
DNA adduct
A DNA adduct is a segment of DNA bound to a cancer-causing chemical .
This process could be the start of a cancerous cell, or carcinogenesis .
DNA adducts in scientific experiments are used as biomarkers of exposure and as such are themselves measured to reflect quantitatively, for comparison, the amount of carcinogen exposure to the subject
organism. Under experimental conditions for study, such DNA adducts are induced by known carcinogens , of which commonly used is DMBA ( 7,12-dimethylbenz(a)anthracene ). The presence of such an adduct indicates prior exposure to a potential carcinogen, but does not by itself
indicate the presence of cancer in the subject animal.
ADME (Absorption, distribution, metabolism, excretion)= Acronym used to describe pharmacokinetics
Absorption- describes the journey of drug traveling from the site of
administration to the site of action
ii. Distribution- describes reversible transfer of the drug from one location to
another within the body
iii. Metabolism= conversion and breakdown of the drug within the body
iv. excretion= process by which metabolic waste is eliminated from an
organism
Environmental Protection Agency :
Environmental Protection Agency : an independent executive agency, not a Department. The
administrator is a member of the Cabinet
Toxic
Substances Control Act TSCA
The Toxic Substances Control Act of 1976 provides EPA with authority to require reporting, record-keeping
and testing requirements, and restrictions relating to chemical substances and/or mixtures.
Certain substances are generally excluded from TSCA, including, among others, food, drugs,
cosmetics and pesticides. TSCA addresses the production, importation, use, and disposal of
specific chemicals including polychlorinated biphenyls (PCBs), asbestos, radon and lead-based
paint.”
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) provides for federal regulation
of pesticide distribution, sale, and use. All pesticides distributed or sold in the United States
must be registered (licensed) by EPA. Before EPA may register a pesticide under FIFRA, the
applicant must show, among other things, that using the pesticide according to specifications
“will not generally cause unreasonable adverse effects on the environment.’’ FIFRA defines the
term ‘‘unreasonable adverse effects on the environment’’ to mean: ‘‘(1) any unreasonable risk to
man or the environment, taking into account the economic, social, and environmental costs and
benefits of the use of any pesticide, or (2) a human dietary risk from residues that result from a
use of a pesticide in or on any food inconsistent with the standard under section 408 of the
Federal Food, Drug, and Cosmetic Act.’’
Resource Conservation and Recovery Act (RCRA)
Resource Conservation and Recovery Act (RCRA) gives EPA the authority to control hazardous
waste from the “cradle-to-grave.” This includes the generation, transportation, treatment,
storage, and disposal of hazardous waste. RCRA also set forth a framework for the
management of non-hazardous solid wastes. The 1986 amendments to RCRA enabled EPA to
address environmental problems that could result from underground tanks storing petroleum
and other hazardous substances. HSWA - the Federal Hazardous and Solid Waste
Amendments - are the 1984 amendments to RCRA that focused on waste minimization and
phasing out land disposal of hazardous waste as well as corrective action for releases. Some of
the other mandates of this law include increased enforcement authority for EPA, more stringent hazardous waste management standards, and a comprehensive underground storage tank
program.
Clean Air Act (CAA)
The Clean Air Act (CAA) is the
comprehensive federal law that regulates air emissions from stationary and mobile sources.
Among other things, this law authorizes EPA to establish National Ambient Air Quality
Standards (NAAQS) to protect public health and public welfare and to regulate emissions of
hazardous air pollutants.”
Clean Water Act (CWA)
“The Clean Water Act (CWA)
establishes the basic structure for regulating discharges of pollutants into the waters of the
United States and regulating quality standards for surface waters. The basis of the CWA was
enacted in 1948 and was called the Federal Water Pollution Control Act, but the Act was
significantly reorganized and expanded in 1972. “Clean Water Act” became the Act’s common
name with amendments in 1972. Under the CWA, EPA has implemented pollution control
programs such as setting wastewater standards for industry. EPA has also developed national
water quality criteria recommendations for pollutants in surface waters. The CWA made it
unlawful to discharge any pollutant from a point source into navigable waters, unless a permit
was obtained. EPA’s National Pollutant Discharge Elimination System (NPDES) permit program
controls discharges. Point sources are discrete conveyances such as pipes or man-made
ditches. Individual homes that are connected to a municipal system, use a septic system, or do
not have a surface discharge do not need an NPDES permit; however, industrial, municipal, and
other facilities must obtain permits if their discharges go directly to surface waters”.
Safe Drinking Water Act (SDWA)
The
Safe Drinking Water Act (SDWA) was established to protect the quality of drinking water in the
U.S. This law focuses on all waters actually or potentially designed for drinking use, whether
from above ground or underground sources. The Act authorizes EPA to establish minimum
standards to protect tap water and requires all owners or operators of public water systems to
comply with these primary (health-related) standards. The 1996 amendments to SDWA require
that EPA consider a detailed risk and cost assessment, and best available peer-reviewed
science, when developing these standards. State governments, which can be approved to
implement these rules for EPA, also encourage attainment of secondary standards
(nuisance-related). Under the Act, EPA also establishes minimum standards for state programs
to protect underground sources of drinking water from endangerment by underground injection
of fluids.”
Animal Feeding
Operations (AFOs)
Animal Feeding
Operations (AFOs) are agricultural operations where animals are kept and raised in confined
situations. An AFO is a lot or facility (other than an aquatic animal production facility) where the
following conditions are met: animals have been, are, or will be stabled or confined and fed or
maintained for a total of 45 days or more in any 12-month period, and crops, vegetation, forage
growth, or post-harvest residues are not sustained in the normal growing season over any
portion of the lot or facility. AFOs that meet the regulatory definition of a concentrated animal
feeding operation (CAFO) are regulated under the NPDES permitting program. The NPDES
program regulates the discharge of pollutants from point sources to waters of the United States.
CAFOs are point sources, as defined by the CWA. To be considered a CAFO, a facility must first be defined as an AFO, and meet the criteria established in the CAFO regulation”.
Comprehensive Environmental Response, Compensation, and
Liability Act – otherwise known as CERCLA
“The Comprehensive Environmental Response, Compensation, and
Liability Act – otherwise known as CERCLA or Superfund – provides a Federal “Superfund” to
clean up uncontrolled or abandoned hazardous-waste sites as well as accidents, spills, and
other emergency releases of pollutants and contaminants into the environment. Through
CERCLA, EPA was given power to seek out those parties responsible for any release and
assure their cooperation in the cleanup. EPA cleans up orphan sites when potentially
responsible parties cannot be identified or located, or when they fail to act. Through various
enforcement tools, EPA obtains private party cleanup through orders, consent decrees, and
other small party settlements. EPA also recovers costs from financially viable individuals and
companies once a response action has been completed. EPA is authorized to implement the
Act in all 50 states and U.S. territories. Superfund site identification, monitoring, and response
activities in states are coordinated through the state environmental protection or waste
management agencies. The Superfund Amendments and Reauthorization Act (SARA) of 1986
reauthorized CERCLA to continue cleanup activities around the country. Several site-specific
amendments, definitions clarifications, and technical requirements were added to the legislation,
including additional enforcement authorities. Also, Title III of SARA authorized the Emergency
Planning and Community Right-to-Know Act (EPCRA).”
Emergency Planning & Community Right-to-Know Act (EPCRA)
“Authorized by Title III of the Superfund Amendments and Reauthorization Act (SARA), the
Emergency Planning & Community Right-to-Know Act (EPCRA) was enacted by Congress as
the national legislation on community safety. This law is designed to help local communities
protect public health, safety, and the environment from chemical hazards. To implement
EPCRA, Congress requires each state to appoint a State Emergency Response Commission
(SERC). The SERCs are required to divide their states into Emergency Planning Districts and to
name a Local Emergency Planning Committee (LEPC) for each district. Broad representation by
fire fighters, health officials, government and media representatives, community groups,
industrial facilities, and emergency managers ensures that all necessary elements of the
planning process are represented.” Key areas: Emergency planning, emergency release
notification, hazardous chemical storage reporting requirements, and toxic chemical release
inventory.
Pollution
Prevention Act PPA
The Pollution
Prevention Act focused industry, government, and public attention on reducing the amount of
pollution through cost-effective changes in production, operation, and raw materials use.
Opportunities for source reduction are often not realized because of existing regulations, and
the industrial resources required for compliance, focus on treatment and disposal. Source
reduction is fundamentally different and more desirable than waste management or pollution
control. Source reduction refers to practices that reduce hazardous substances from being
released into the environment prior to recycling, treatment or disposal. The term includes
equipment or technology modifications, process or procedure modifications, reformulation or
redesign of products, substitution of raw materials, and improvements in housekeeping,
National Response
Center (NRC)
The National Response
Center (NRC) is a part of the federally established National Response System and staffed 24
hours a day by the U.S. Coast Guard. It is the designated federal point of contact for reporting
all oil, chemical, radiological, biological and etiological discharges into the environment,
anywhere in the United States and its territories. The NRC also takes maritime reports of
suspicious activity and security breaches within the waters of the United States and its
territories. Reports to the NRC activate the National Contingency Plan and the federal
government’s response capabilities. It is the responsibility of the NRC staff to notify the
pre-designated On-Scene Coordinator assigned to the area of the incident and to collect
available information on the size and nature of the release, the facility or vessel involved, and
the party(ies) responsible for the release. The NRC maintains reports of all releases and spills in
a national database.”
Department of Health and Human Services :
FDA FFDCA
Federal Food, Drug, and Cosmetic Act (FFDCA)
“Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) authorizes EPA to
set tolerances, or maximum residue limits, for pesticide residues on foods. In the
absence of a tolerance for a pesticide residue, a food containing such a residue is
subject to seizure by the government. Once a tolerance is established, the residue level
in the tolerance is the trigger for enforcement actions. That is, if residues are found
above that level, the commodity will be subject to seizure. In setting tolerances, EPA
must make a finding that the tolerance is “safe.” Safe is defined as meaning that there is
a “reasonable certainty that no harm will result from aggregate exposure to the pesticide
residue.” To make the safety finding, EPA considers, among other things: the toxicity of
the pesticide and its break-down products, aggregate exposure to the pesticide in foods
and from other sources of exposure, and any special risks posed to infants and children.
Some pesticides are exempted from the requirement to have a tolerance. EPA may
grant exemptions in cases where the pesticide residues do not pose a dietary risk under
reasonably foreseeable circumstances.”
Department of Health and Human Services :
FDA
Food Quality Protection Act (FQPA)
The Food
Quality Protection Act (FQPA) was passed unanimously by Congress and then signed
into law by President Clinton on August 3, 1996. The FQPA amended the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food Drug and
Cosmetic Act (FFDCA) and thus fundamentally changed EPA’s regulation of pesticides.
With regard to tolerances, the FQPA requires that EPA:
-make a safety finding when setting tolerances, i.e., that the pesticide can be used with
“a reasonable certainty of no harm;” use this new safety standard to reassess, over a 10-year period, all pesticide tolerances
that were in place when the FQPA was signed;
-consider the special susceptibility of children to pesticides by using an additional tenfold
(10X) safety factor when setting and reassessing tolerances unless adequate data are
available to support a different factor;
-consider aggregate risk from exposure to a pesticide from multiple sources (food, water,
residential and other non-occupational sources) when assessing tolerances; and
-consider cumulative
exposure to pesticides that have common mechanisms of toxicity.
To implement these FQPA requirements, EPA needed to develop methodologies to
perform more refined pesticide risk assessments, to better reflect real-world situations.
Thus, in a short timeframe, EPA had to develop a variety of new science policies, which
included new guidelines on:
-Use of the 10X safety factor.
-Drinking water exposure.
-Residential exposure.
-Aggregate exposure and risk assessment.
-Cumulative risk assessment for pesticides with a common mechanism of toxicity.
Using these newly-developed methodologies, EPA completed the reassessment of the
9,721 pesticide tolerances during the 10-year timeframe, as required. As a result, EPA
revoked or modified almost 4,000 tolerances.
The FQPA also required EPA to:
-Expedite approval of pesticides meeting the FQPA definition of reduced risk.
-Give special consideration to minor uses of pesticides (i.e., uses for which pesticide
product sales produce small revenues and thus, the registrant might decide to not
generate the data needed to support the minor use).
-Provide a list of pests of significant public health importance (issued in 2002).
-Expedite the review of applications to register antimicrobial pesticide products.
-Screen pesticides for disruption to the endocrine system.
-Significantly, FQPA requires the periodic review cycle for pesticide registrations.
Changes in science and pesticide practices occur over time, and these periodic review
cycles make sure that as changes occur, pesticide products can continue to be used
safely. The Registration Review Program began in 2006 with the goal of reviewing each
pesticide’s registration every 15 years to make sure that the pesticide still meets the
FIFRA standards for registration.”
DHHS
CDC/ATSDR
Agency for Toxic Substances and Disease Registry (ATSDR),
“ATSDR
protects communities from harmful health effects related to exposure to natural and
man-made hazardous substances. We do this by responding to environmental health
emergencies; investigating emerging environmental health threats; conducting research
on the health impacts of hazardous waste sites; and building capabilities of and
providing actionable guidance to state and local health partners.”
