tox 2 finals Flashcards
what is food toxicology
Food toxicology is the study of the nature, properties, effects, and detection of toxic substances in food, and their disease manifestation in humans
safety concerns should focus on….
safety concerns should focus on both the nature of the substance and its intended conditions of use
Tox studies focus on what portion the most
- focus on digestion and metabolism occurring in the GI tract
-The reason for this focus is that in most cases it is not the ingested substance that is absorbed through the GI tract; it is products of its digestion that are absorbed.
the two major problems in regulation are
Two major problems
Toxic colors and preservatives “
Patent “quack” medicines
What is GRAS
Generally regarded as safe
Scientific experts determine whether a substance that is to be added to a food is GRAS.
In addition to GRAS the FD&C Act provides a class of substances that are regulated as food additives, which are not generally recognized to be safe.
Hence there is a legal distinction between GRAS and Food additives
what is poison squad
first regulatory agency that looked after certain meals
what was the upton sinclair jungle 1906
Novel about meat processing industry
Unsanitary conditions and practices for workers
Rats in meat plants
what was he federal meat inspection act
Mandatory inspection of livestock before slaughter
Mandatory postmortem inspection of every carcass Sanitary standards established for slaughterhouses and meat processing plants
Authorized U.S. Department of Agriculture ongoing monitoring and inspection of slaughter and processing operations.
what was the pure food and drug act
First comprehensive federal food law
Considerable opposition from industry
Many legal cases pointed out strengths and weakness in law
Many good things
Needed work
problems:
Food adulteration still common
Few purity food standards
Food color, water, grass seed, pectin = fruit jam
Limited analytical techniques
Weak on food & drug safety
Burden of proof on FDA
what was elixir of sulfanilamide
raspberry flavored death
medicine that was taken
children died
Food drug and cosmetic act
Included cosmetics, therapeutic devices
Pre-market safety testing of drugs
Toxic substances prohibited in foods unless unavoidable or required in processing Authority for factory inspections
Proof of fraud no longer required to stop false claims
-Previously only the maker had to believe efficacy
Safe tolerances were authorized for pesticide residues
Standards were developed for many foods
what was the delaney clause
No chemical can be added to food or animal feed that has been shown to be a carcinogen by appropriate tests (animal studies)
Zero tolerance/zero risk
Dilemma for cumulative and non-cumulative pesticides - Sections 408 and 409
Food Quality Protection Act 1996
Abolished Delaney Clause for pesticides
Negligible risk (1 in a million ) for carcinogens, de minimus No residue in edible portion
10x safety factor for children
Risk cup
what are tolerances
A food may be declared unfit if it contains unavoidable contaminant that may render the food injurious.
But, an unavoidable contaminant in food, need only pose a risk to be found unfit and subject to FDA action.
At times, foods containing unavoidable contaminants cannot be banned.
Under provisions of Sec 406 of the FD&C Act, the quantity of the unavoidable contaminant in food may be limited by regulation.
Ex: Action levels for Aflatoxin in peanuts, grain, and milk.
what are food additives
A substance which may, by its intended use, become a component of food, either directly or indirectly, or which may otherwise affect the characteristics of food.
Includes any substance intended for use in producing, manufacturing, processing, preparing, treating, packaging, transporting or holding food, and any source of radiation intended for such use
what are the rules for exempt chemicals
GRAS (Generally Recognized as Safe)
From scientific studies or wide usage
Salt, vitamins, etc.
GRAS - qualified experts determined safe
May not be FDA decision (GRAS)
Company can self-proclaim (GRAS)
“Prior Sanctioned” before 1958
Prior sanctioned – approved by FDA/USDA prior to 1958
Sodium nitrite, etc.
what are regulated food additives
Food additives that are not color, or GRAS, or prior sanctioned
Require FDA approval
-Scientific data that no harm will occur
“Redbook” guidelines
Must justify function
32 categories (C&D)
food addtives have to go through FDA approval
what are color additives
Same testing as food additives
Not eligible as GRAS
Tested at all FDA concern levels
-Two types
=Certified - by FDA chemists for purity
=Exempt - mostly naturally occurring
what are certified color additives
Prefix of FD&C
Two exemptions: Orange C, Citrus Red 2
Every batch must be FDA certified
Aromatic amines, aromatic azos
Unusually nontoxic for these compounds
what are exempt color additives
Usually naturally occurring
Dried algae, beet powder, grape skin extract, fruit juice, caramel, etc.
Lack precise chemical identity
Fade readily, lack intensity and uniformity
Higher levels required
Used less (except caramel)
what is reference dose
An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used.
what is ADI
Acceptable Daily Intake (ADI): The amount of a chemical a person can be exposed to on a daily basis over an extended period of time (usually a lifetime) without suffering deleterious effects
what are indirect food additives
not directyy added to food
may enter food through migration of packaging materials holding containers or processing surfaces
cans plastics
indirect food additives toxicity testing
Negligible migration (< 0.05ppm) and EDI < 0.15mg/person/day
Acute toxicity studies only
Migration 0.05-1.0ppm
Subchronic studies; 2 species
Migration > 1.0ppm
Chronic studies; 2 species
Carcinogenicity
Multigenerational reproduction
Teratology
what is DSHEA
The Dietary Supplements Health and Education Act (DSHEA) was established in 1994 to provide the legal framework specifically for dietary supplements
Under the DSHEA, no claim can be made for a dietary supplement to treat, cure or mitigate a disease.
However, a dietary supplement can make claims that it affects or maintain the structure or function of the body
FDA Carcinogenic Constituent Policy For Non-functional Carcinogenic Contaminants of Food Additives
Delaney is not invoked
Health effects may be negligible
RA model
Upper bound lifetime risk in humans < 1 in million above background
-Many conservative estimates made in model
-Possibly over estimates risk by million-fold
interpretation of delaney: Food additives
Risk Assessment cannot be used if food additive is carcinogenic
Zero tolerance policy
Very strict regulation
FDA requires clear, unequivocal, reproducible evidence for cancer
Few substances banned
Must be primary carcinogen
Secondary carcinogenesis not considered evidence
1959 Cranberrry incidecet
Aminothiazole residues detected in cranberry products (Delaney Clause) Recall of cranberry products during Thanksgiving - Public impact!
1959 Cranberrry incidecet
Aminothiazole residues detected in cranberry products (Delaney Clause) Recall of cranberry products during Thanksgiving - Public impact!
The delaney clause for food additves shwos
Applies to: Regulated food additives, color additives and drugs
Does not apply to: Unavoidable contaminants, GRAS substances, prior sanctioned ingredients or non-functional trace contaminants
what is secondary carcinogenesis
Nutritional, hormonal, physiological imbalances are secondary causes of cancer
Secondary carcinogens only contribute to increase (promote) effect
No evidence of direct genotoxicity
Example: BHA
=Chronic irritation = tissue damage = hyperplasia = cell proliferation = increased =chance for mutation and cancer
substances banned by delaney
Packaging materials - Flectol H, mercaptimidazoline
Food additives - safrole, cinnamyl anthranilate, thiourea, diethylpyrocarbonate (forms urethane) Primary carcinogens
what are adverse reactions to food
Definition: General term that can be applied to a clinically abnormal response attributed to an ingested food or food additive
Characteristics/Example: Any untoward pathological reaction resulting from ingestion of a food or food additive. May be immune mediated.
what are food allergy symptoms
Respiratory = asthma, wheezing, bronchiospasms, dyspnea (shortness of breath) Cutaneous = urticaria (hives), eczema, rash, pruritis
Gastrointestinal = vomiting, diarrhea, abdominal pain
Inflammation, vasoconstriction, hypotension, chest pain, nausea
Other = anaphylaxis
Mild and annoying to fatal
Depend on amount ingested and length of time from initial exposure Not all symptoms in all people
what is food intolerance
Definition: A general term describing an abnormal physiologic response to an ingested food or food additive; this reaction may be an immunologic, idiosyncratic, metabolic, pharmacologic, or toxic response
Characteristics: Any untoward pathologic reaction resulting from ingestion of a food or food additive. May be immune-mediated.
Example: Celiac disease (intolerance to wheat, rye, barley, oats)
what is Food Toxicity (Poisoning)
Definition: A term used to imply an adverse effect caused by the direct action of a food or food additive on the host recipient without involvement of immune mechanisms. This type of reaction may involve non immune release of chemical mediators. Toxins may be contained within food or released by microorganisms or parasites containing food products
Characteristics/examples: Not immune mediated. May be caused by bacterial endo- or exotoxin, fungal toxin, tetrodotoxin from pufferfish, domoic acid from mollusks, histamine poisoning from fish, nitrate poisoning from processed meat
what is food idiosyncrasy
Definition: A quantitatively abnormal response to a food substance or additive; this reaction differs from its physiologic or pharmacological effect and resembles hypersensitivity but does not involve immune mechanisms. Food idiosyncratic reactions include those which occur in specific groups of individuals who may be genetically predisposed.
Characteristics/examples: Not immune-mediated, Favism (hemolytic anemia related to deficiency of erythrocytic glucose-6-phosphate dehydrogenase), fish odor syndrome, lactose intolerance, asparagus urine, red wine intolerance
Anaphylactoid Reaction to a Food
Definition: An anaphylaxis-like reaction to a food or food additive as a result of non-immune release of chemical mediators. This reaction mimics the symptoms of food hypersensitivity (allergy)
Characteristics/examples: Not immune mediated. Scombroid poisoning, sulfite poisoning, red wine sensitivity
what is pharmalogical food reaction
Definition: An adverse reaction to a food or food additive as a result of a naturally derived or added chemical that produces a drug-like or pharmacologic effect in the host
Characteristics/Examples: Not immune mediated. Tyramine in patients treated with MOA inhibitors, fermented food in disulfiram treated patients
what is metabolic food reaction
Definition: Toxic effects of a food when eaten in excess or improperly prepared
Examples: Glycyrrhizism, vitamin A toxicity, goitrogens
what is risk assessment
The systematic scientific characterization of potential adverse health effects resulting from human exposures to hazardous agents or situations
what are risk assessments requirements
Qualitative information about the strength of the evidence and the nature of the outcomes
Quantitative assessment of the exposures
Host susceptibility factors
Potential magnitude of the risk
Description of the uncertainties in the estimates and conclusions
Describe Characterization of Risk
Risk assessment often results in an overly precise risk estimate
Frequent ignorance of:
Crucial information about mechanism of toxicity
Species variability
Inconsistent findings across studies
Multiple variable health effects
Means of avoiding or reversing the effects of exposures
What is the risk assessment paradigm
Risk Characterization
Estimates the incidence of a health effect under the various conditions of exposure described in exposure assessment
Performed by combining the hazard identification, exposure assessment, and dose-response assessment
Describes the summary effects of the uncertainties in the preceding steps
Qualitative risk characterization
-Narrative; semi-quantitative terms such as “negligible”, “minimal”, “moderate”, “severe”, and “acceptable”
-Comparisons to common hazards and risks: “less than”, “equal to”, or “greater than”
Quantitative risk characterization expresses hazard and risk in numerical terms; amount of hazard per unit dose or exposure of an agent, e.g., percent change in response for each mg/kg of toxic agent
4 key steps in risk assessment
Hazard identification, dose response assessment, exposure assessment and risk chrachterization
what is risk management
Process by which policy actions are chosen to control hazards identified in risk assessment
Risk managers consider the following:
Scientific evidence
Engineering, economic, social, and political factors
Risk Management framework 6 stages
1Formulating the problem in a broad public health context
2Analyzing the risks
3Defining the options
4Making risk-reduction decisions
5Implementing those actions
6Evaluating the effectiveness of the actions taken
What is risk communication
Challenging process of making risk assessment information comprehensible to the community (lawyers, elected officials, workforce, environmentalists)
what is the national research council
Risk Assessment in the Federal Government: Managing the Process (“The Red Book”)
Detailed steps of hazard identification, dose-response assessment, exposure analysis, and characterization of risks
Provides consistent framework for risk assessment across agencies
-Research feeds into risk assessments
-Crucial data uncertainty drives research
-New research findings modify risk assessment
Often, extrapolations must go beyond observations of actual effects and reflect different tolerances for risks – this generates controversy!
what are SARS
structure and activity relationships
life time rodent bioassays can be expensive and long
SARs can provide an alternative
Can be used for complex mixtures
Difficult to predict activity across chemical classes and multiple toxic endpoints
Often computerized programs which utilize databases of known toxicological effects
what are in vitro and short term tests
bacterial mutaiton assay
Transgenic knockout mice
- the ability of a substnace to hinder the growth of bacteria
- If the growth is present in the bacteria treated with itm it maens something is altering DNA, which is a possible cancer risk
what was saccharin
used to kill rodents, it can be used as a sweetner in humans
why do we use animal bioassays
Chemicals that cause effects (e.g. tumors) in animals will cause the same effects in humans
what are the parts of the animal bioassay
Two species and both sexes
Lifetime exposure
Number of dose levels (to investigate multiple orders of exposure magnitude)
Detailed histopathology
Addition of mechanistically oriented short-term tests to predict response at environmentally relevant doses
how is a epidemiological study a good study
A well-conducted epidemiologic study with a positive association between exposure and disease is the most convincing line of evidence for human risk
limitations are
Hypotheses are often weak
Exposure estimates are often crude
Multiple exposure levels
Often detailed information on few persons or limited information on large numbers of persons
Contributions from lifestyle factors (smoking and diet)
Individual variation
what are 3 types of epidemiology studies
Cross-sectional studies: Survey groups of humans to identify risk factors and disease
Cohort studies: Evaluate individuals selected on the basis of their exposure to an agent under study
Both Cross-sectional and Cohort studies monitor disease-free individuals to determine the rates at which they develop disease
Case-control studies: Subjects are selected on the basis of disease status. Disease cases and disease-free individuals are compared with respect to exposure histories to determine key consistent/inconsistent features in their exposure histories.
what is the threshold approach vs non threshold approach
Threshold Approach: non-cancer endpoints
Non-Threshold Approach: cancer endpoints
The significance in Dose-response curves depend on?
Depends on:
Number of dose levels tested
Number of animals
Background incidence of the average response in non-exposed control groups
what are NOAELS
NOAELs serve as the basis for risk assessment calculations
Reference Dose (RfD): Daily exposure level assumed to be without adverse health impact on the human population
Acceptable Daily Intake (ADI): Daily intake of a chemical during an entire lifetime that appears to be without appreciable risk on the basis of all known facts
-RfD or ADI = NOAEL / uncertainty factors or modifying factors
what are uncertainty factors
these factors allow for inter species varaiblity as well as experimental inadequcies
- usually 10
but animal to human and human to human variability is 100
what is wrong with the NOAEL approach
NOAEL must be one of the doses tested
Once this dose is identified, the rest of the DR curve is often ignored (slope)
Fewer animals results in larger NOAELs and therefore larger RfDs
describe exposure assessment
Frequently identified as key area of uncertainty in overall risk determination
Determination of the source, type, magnitude, and duration of contact with the agent of interest
Hazard does not occur in the absence of exposure!
May often consider how much of the agent will reach target tissues
what is the purpose of ecological risk assessments
Ecological Risk Assessments help risk managers determine which course of action to take for ecosystems that have been, or could be, exposed to stressors
what are the steps for ecological risk assessment ?
Problem formulation provides the foundation for the risk assessment
During analysis, risk assessors gather data to characterize exposure, and characterize the effect these stressors might have on the ecological entity
Then you do risk charachterization
what are the steps for ecological risk assessment ?
Problem formulation provides the foundation for the risk assessment
During analysis, risk assessors gather data to characterize exposure, and characterize the effect these stressors might have on the ecological entity
Then you do risk charachterization
what is persistence
A substance is considered to be persistent in a given medium if it resists physical, biological and chemical degradation.
The degradation of a substance in a given medium is usually expressed by its overall half-life.
what is bioaccumulation
Bioaccumulation of a substance is its capacity to accumulate in the tissues of organisms, either through direct exposure to water, air or soil, or through consumption of food.
what is bioaccumulation
Bioaccumulation of a substance is its capacity to accumulate in the tissues of organisms, either through direct exposure to water, air or soil, or through consumption of food.
what is PEC
Predicted exposure concentration
For new substances, the expected environmental concentrations are calculated using exposure models and a realistic prediction of the anticipated market volume of the product(s) for which the ingredient is intended.
The exposure assessment results in estimated concentrations for the relevant compartments. For consumer products, water and soil are the most important compartments. Most consumer product chemicals generally have low volatility, which means that air releases are relatively limited.
This is the most complex
What is the PNEC value
Predicted no exposure concentration
the toxicity of the ingredient to certain environmental “indicator species” is assessed
example:For the aqueous environment, indicator species are typically a freshwater fish, freshwater invertebrate and freshwater green algae
what is qsar
The toxicity data for environmental indicator species are obtained from the literature, or from laboratory testing
In some instances, toxicity estimates from Quantitative Structure-Activity Relationships (QSAR) may suffice, such as for a low volume ingredient or an ingredient with very low toxicity or both
However, the uncertainty associated with QSAR estimates is much higher than with measured values, and this uncertainty has to be taken into account in the risk assessment via the use of assessment factors
These factors are used to divide the lowest available effect level (or no observed effect level) to derive a Predicted No Effect Concentration (PNEC) for the ecosystem
what is analytical toxicology
Applies tools of analytical chemistry in order to estimate exposure to chemicals in living organisms
what is forensic toxicology
Utilizes toxicology for purposes of the law
Identification of a chemical that may have served in inflicting death or injury
Techniques of analytical chemistry are used extensively in both disciplines
what does a postmortem investigation entail?
Qualitative and quantitative analysis of drugs or poisons in biological specimens collected at autopsy
Interpretation of analytic findings in regard to the physiologic effects of the detected chemicals on the deceased
Cause of death: Determined by medical examiner and coroner
what are 3 steps of investigation of lethal poisoning
Obtain the case history and suitable specimens
Conduct suitable toxicologic analyses on available specimens
Interpret the analytic findings
what is forensic urine drug testing?
Initial testing performed with immunoassays on high-speed, large-throughput analyzers
Many individuals attempt to mask drug use through:
Ingestion of diuretics
Adulteration of the specimen directly with bleach, vinegar, or other products that interfere with initial immunoassay tests
what is the analytic role in clinical toxicology
Aids in diagnosis and treatment of toxic incidents
Clearly identifies nature of toxic exposure
Measures amount of absorbed toxic substance
Allows the clinician to relate signs and symptoms to the anticipated effects of the toxic agent
what is clinical toxicology
Rapid quantitative determination of toxic agents are necessary in instances of suspected overdose
what is plasma monitoring
is employed to verify that a patient is receiving the proper dose of a therapeutic drug
Monitoring of plasma or serum concentration at regular intervals will detect if one of these variables has changed and needs correction
When various factors are constant, administration of the same dose of drug at regular intervals produces a steady-state concentration
what is biological monitoring
- commonly done in factories
- monitor a worker directly, which is better than the environment for exposure
– shows what has been actually absorbed
Analytic methods must be capable of separating a family of chemical agents and their metabolites
what are the cardinal rules of treatment of poisoning cases
Remove any unabsorbed material
Limit absorption of additional poison
Hasten the elimination of the poison
Clinical toxicologists monitor the amount of toxic agent remaining in circulation, and measure what is excreted
what is toxic syndrome
Toxic syndrome: collections of clinical signs that, taken together, probably are associated with exposure to certain classes of toxicologic agents
This classification allows the initiation of rational treatment even if the exact nature of the toxin is unknown
what is anion gap
Difference between serum sodium concentration and the sum of serum chloride (Cl) and bicarbonate (HCO3)
Normal: <12
An elevated anion gap suggests systemic toxicity from “AT MUD PILES”
what is an osmol gap
Difference between measured serum osmolarity and serum osmolarity calculated from clinical chemistry measurements of sodium ion, glucose, and BUN concentrations
Normal: < 10 mOsm
Elevated osmol gap suggests presence of an osmotically active substance not accounted for by sodium, glucose or BUN concentrations
what are steps of intervention for further poison absorption
Intervention:
Inhaled substances: Removal of the patient from the toxic environment
Topical exposure: Removal of toxin from skin
Oral Poison: Induction of emesis with syrup of ipecac (discontinued as of 2010), gastric lavage (aspiration of stomach contents), oral administration of activated charcoal
how do you enhance poison elimination
- employed following absorption of toxin into systemic circulatoin
Alkalinization of urine
Enhances renal clearance of weak acids
Infuse basic solution into the blood → increase pH of urine filtrate → ionization of weak acids → prevents reabsortion of toxin by renal tubules → elimination
Acidification of urine is not used as acute renal failure and acid-base disturbances are associated with acidification
what is hemodialysis
Filtration of blood past a dialysis membrane
Drugs bound to plasma proteins may not pass through dialysis membrane and into the dialysis fluid and therefore aren’t eliminated!
Other toxins may accumulate in tissues, making dialysis useless
what is hemoperfusoin
Blood is filtered through a chamber containing activated charcoal or Amberlite resin.
Allows elimination of toxins bound to plasma proteins
what is plasma exchange/pheresis
Removal of patient’s plasma with replacement by donor plasma
May remove high-molecular weight and/or plasma protein-bound toxins
Rarely used in clinical toxicology
what is plasma exchange/pheresis
Removal of patient’s plasma with replacement by donor plasma
May remove high-molecular weight and/or plasma protein-bound toxins
Rarely used in clinical toxicology
Describe the use of antidotes in poisoning
Mechanisms of antidotes can vary dramatically
Chelators
Receptor antagonists (to prevent over-stimulation)
Competitors (to compete for binding sites)
Some antidotes induce biological systems to provide additional binding sites for the toxin thereby increasing the patient’s detoxifying capacity for that toxin
describe size exclusion gel chromatography
Column is packed with material having precisely controlled pore sizes
The sample is simply screened or filtered in the column
Large molecules elute first as small molecules take a longer time period to travel through the column
what is the ion exchange
Used exclusively with ionic or ionizable samples
The stationary phase has an ionically charged surface of opposite charge to the sample
The stronger the charge of the sample, the stronger the attraction to the ionic stationary surface
what is the ion exchange
Used exclusively with ionic or ionizable samples
The stationary phase has an ionically charged surface of opposite charge to the sample
The stronger the charge of the sample, the stronger the attraction to the ionic stationary surface
what is the bonded phase
This mode makes use of differences in polarity and the “like
dissolves like” principle
in normal phase
- the normal stationary phase is polar
a less polar or non poar solven is used as the mobile phase
the more polar compounds inthe samele will be attachted to the stationary phase and less polar will elute first
the reverse phase
The stationary phase is non-polar
The mobile phase is more polar than the stationary phase
The less polar compounds in the sample will be attracted to the stationary phase and the more polar compounds will elute first
what are accepted methods that target only acute effects
3T3 NRU Phototoxicity test
Skin corrosivity test
hERG Assay
what is genotoxicity
Genotoxicity: A broad term that refers to any deleterious change in the genetic material regardless of the mechanism by which the change is induced
what is genetic endpoint
Genetic Endpoint: The precise type or class of genetic change investigated (e.g., gene mutations, chromosomal aberrations, DNA-repair, DNA-Adduct formation, etc.)
what is a mutagen
An agent that produces DNA damage and other permanent genetic alterations, with changes in one or more DNA base pairs (point mutations, frameshift mutations, deletions)
what is a clastagen
Clastagen: An agent that produces gross structural or numerical (aneugenic) changes of chromosomes (chromosomal aberrations, e.g., micronucleus), usually detectable by light microscopy
what is unscheduled DNA synthesis
Damage to DNA requires cell to manufacture new DNA to compensate for loss or damage
What is DEREK
Deductive Estimation of Risk from Existing Knowledge
Key Principle - DEREK is not a database system but a rulebase system. Each rule describes relationship between a structural feature (toxicophore) and its associated toxicity.
DEREK is a knowledge-based expert system for the qualitative prediction of toxicity, mainly for genotoxicity/carcinogenicity
the benefit of this is no drug needed just structure, it can see the metabolites and what will be created
sometimes its too senseive
if a compounds does not hit on derek,its likely unlikely to be mutagenic
what are standard battery of genotoxicity tests
Test for gene mutation in bacteria (Ames)
Evaluation of chromosomal damage with mammalian cells (in vitro MNT or in vitro mouse lymphoma test)
An in vivo test for genotoxicity, generally a test for chromosomal damage using rodent cells (in vivo rodent MNT)
describe the micronucleus test
Can be performed in vitro or in vivo
Screens for clastogenic/aneugenic activity in mouse lymphoma cells, +/- liver homogenate (S9) or in whole animal
Additional detection of apoptotic/necrotic activity and cytostatic effects
Uses a small amount of drug (in vitro) and produces results quickly
what does the HCA test for
cytogenic test for detection of chromosomal damage in human lymphocytes
Aneugenic Potential: Determine if there is an increase or decrease in the number of chromosomes
Clastogenic Potential: Look for morphological changes in the
chromosome
what does the HCA test for
cytogenic test for detection of chromosomal damage in human lymphocytes
Aneugenic Potential: Determine if there is an increase or decrease in the number of chromosomes
Clastogenic Potential: Look for morphological changes in the
chromosome
what is the ML/TK test
Test for induction chromosomal aberrations and gene mutations in mouse lymphoma cells, +/- liver homogenate (S9)
Requires minimal drug and produces results quickly
it measures resistance to TFT
if normal cell put into TFT containing medium they die
if you put in mutated cells, they can survive due to lack of thymidine kinase activity (TFT resistance)
-Large colonies are indicative of gene mutation
-Small colonies are indicatives of chromosomal mutations
what is phospholipidosis
Drug-induced PL is a generalized condition in human and animals, induced by cationic amphiphilic drugs (CADs) and some cationic hydrophilic drugs (like the aminoglycoside gentamicin).
PL may occur in virtually any tissue. PL is characterized by accumulation of one or several classes of phospholipids within cells.
It is considered to be primarily an adaptive process to CAD exposure rather than a toxic response
what is photoxicity
Phototoxicity is a light-induced, non-immunologic skin response to a photoreactive drug or chemical.
Most phototoxic agents are activated in the range of 320 to 400 nm.
Chemical photosensitivity: adverse cutaneous reaction from drugs at the same time that a person is exposed to UV or visible radiation.
what is photo allergy?
is an acquired altered reactivity of the skin that is dependent on antigen-antibody or cell-mediated hypersensitivity.
People who take medications or use topical agents known to be sensitizing should avoid all sun exposure. There is a wide range of severity: uncomfortable, serious, or even life-threatening
compare uvb to uva
UV-B is cause of burning tanning aging and carcinogenity.
UV-A is erythrogenic and melanogenic; associated with photosentization.
what is a in vitro photo toxicology study
3T3 Fibroblast Neutral Red Uptake Assay
3T3 Fibroblast Neutral Red Uptake Assay does what
Fibroblasts are incubated, and with control substance or test substance, exposed to UVA radiation and UVB
Then cells are washed and incubated with neural red die
Less cells die form UVA and drug,
Measurement of neutral red uptake into cells. Unless the cells are damaged from the drug/UVA light, the red dye will remain trapped in the cells and idicates lack of phototoxicity.
what is regulatory toxicology
Use data from descriptive and mechanistic toxicology to perform risk assessments.
Concerned with meeting requirements of
regulatory agencies.
what was the vaccine act and the biologics act
Bad Smallpox Vaccine
First Federal Law Dealing with Consumer Protection and Drugs
Short-lived
Passed after Deaths Due to Bad Diphtheria Antitoxin
what was the 1906 act
Basic Structure of the FDA
Followed in Broad Outline Today
Authority over Interstate Shipment of Adulterated Foods and Drugs
Narrow Use of Commerce Clause Power
what is MDA 1976
Medical Device Amendments
Passed after Pacemaker and other Medical Device Scandals
Risk Class Regulation
New Devices Must Be Safe and Effective
510(k) Grandfathering
-Substantially Equivalent to a 1976 Device
-Most Devices Qualify
what is FSIS
Food safety inspection service meat poultry and eggs
what is the EPA
Intended to streamline and strengthen regulation of pesticides
Consolidated responsibilities of several agencies into EPA
Intent to protect health and environment related to air, water and soil pollution withrisk - benefit considerations
what was FIFRA
Premarket testing of pesticides
Efficacy and safety
Environmental impact
Establishing Testing Procedures
-General and Special
Establish tolerances
Post-market environmental surveillance monitoring
Registration of pesticide-producing facilities
Classification of pesticides (restricted vs. general)
Banning pesticides
Risk - benefit evaluation
toxic chemical substance act
Intended to bring industrial chemicals under oversight of EPA
Not to regulate all chemicals, only those that pose unreasonable risk to health and environment
Prevent reoccurrence of industrial exposures and accidents (asbestos, MeHg, vinyl chloride, PCB)
what was TSCA
Pre-manufacture testing of new chemicals or new uses of old chemicals (not pesticides or food additives, ATF)
Covers manufacture, use, distribution and disposal of any toxic substance
Risk/benefit analysis
what was the resource conversion and recovery act
Controls generation, shipping, storage, treatment, record keeping related to hazardous waste
Identifies hazardous wastes
Sets guidelines for testing hazardous wastes
Designs HW storage facilities
what is NIOSH
national institute for occupational safety and health
what is osha
Health standards in the workplace
Includes toxic chemicals, stress, noise
Train personnel, educate workers
Action is all retrospect
Must prove problem exits
what is CPSC
Any product for use, consumption or enjoyment in a recreational or other manner used in and around personal residences or school
Protect public from risk/injury from consumer products
Regulates mostly by labeling
Sets standards and evaluates safety of consumer products
flammable clothing, childproof lids, household chemicals
Excludes items covered by other agencies (pesticides, alcohol, drugs)
Lacks pre-market authority
what is the IACUC
Institutional Animal Care and Use Committees (IACUC) MUST be established at each institution using animals for research, testing, and education
they hire a vet,
animals can only be used after approval form IACUC
the people involved must get raining
what was ICCVAM
an act to establish, where feasible, to revitalize acute and chronic testing
everything under one roof
what is reach
REACH = Registration, Evaluation, Registration of Chemicals
Expanded European Chemicals Bureau
Public database of non-confidential information
