Midterm 2 (tox) Flashcards
what is the regulatory agency for Vet pharmaceuticals
veterinary drugs directorate (VDD), health canada
- is covered under the food and drugs act legislature
Extralabel drug use is the use of a drug that is unapproved or not approved to be used in that specific manner. is this more or less common in animals
more common - may be used due to a lack of effective or approved products or economic considerationa
what must you consider when doing ELDU in animals
the development of antimicrobial resistance, drug residues in food for human consumption
category one vs category two antimicrobials
category one is very high importance, the preferred treatment option for serious human infections which have no or limited alternative treatment options
category two is high importance, the preferred treatment for serious human infections but there are alternatives that can be used
category one should not be used for ELDU
maximum residue limits (MRLs)
the max level of a residue that could remain in the tissue or food product of a food-producing animal that has been treated with a veterinary drug, with no adverse health effects expected if a human were to ingest this daily
what types of drugs used in animals are not routinely monitored for MRLs
those with low toxicity, those that are poorly absorbed or have low bioavailability, those that are rapidly metabolized or excreted, those which are infrequently used (used once or twice in an animals lifespan)
how are maximum residue limits determined
first you have to identify the residue of interest, is it the original chemical or one of its metabolites?
do metabolism studies in the food-producing animal to determine its half life and that of its metabolites
do carcinogenicity and toxicity studies to determine the ADI
do withdrawal periods to get insight into how the residue is depleted in the animal
what does the vet pharmacovigilance program do
monitors:
- safety and efficacy of vet drugs
- safety of humans handling these drugs
- safety of consuming food products from treated animals
excipients
ingredients with no real pharmacological effects
label requirements for NHP
product name and license number
quantity of product in the bottle
full list of medicinal and non-medicinal ingredients
recommended use (purpose or health claim)
warnings of possible adverse reactions
can NHP bypass clinical trials
NHP can bypass clinical trials if there is an abundance of published studies, articles, or traditional resources already describing the therapeutic action
who is responsible for the monitoring of adverse effects of NHP
product license holders are responsible for adverse event monitoring and must report them to health Canada
regulatory agency for cosmetics
Healthy environments and consumer safety
regulatory agency for NHP
natural and non-prescription health products directorate, Health Canada
T/F if a cosmetic has no prohibited or restricted ingredients, it does not need to provide testing data to health Canada before first sale
true - if it has no prohibited or restricted ingredients the manufacturer only needs to inform health Canada within 10 days of first sale
products which fall in the cosmetic-drug interface can be regulated by …
cosmetic regulations, food and drug regulations, as well as NHP regulation
three ways to distinguish between a cosmetic and a drug
- proposed claim - claims of treatment, diagnosis, prevention, or restoration are often drugs
- composition - ingredients or concentrations may classify a product as a drug (corticosteroids)
- level of action - if something only acts superficially (no systemic absorption it is likely cosmetic
medical device
something that intends to affect the structure or functioning of the body without chemical action or dependence on metabolism - these often require additional non-clinical lab studies like biocompatibility, stress wear, shelf life, microbiology and immunological
regulatory agency for medical devices
Medical Devices Directorate (MDD - Health Canada)
- provides information for Canadians to make informed decisions, does investigational testing authorizations to make sure that studies are well designed and safe for participants, responsible for assessing safety, efficacy and post-market surveillance
- makes exceptions for medical devices in extenuating circumstances
classification of diagnostic medical devices
1 - general in-vitro lab equipment and reagents (ex - bacterial growth media)
2 - low public health risk - used to detect infectious agents which are not known to be easily propagated
3 - moderate public health risk or high individual risk - where an erroneous result may result in an imminent life-threatening situation ( ex - a missed diagnosis for meningitis or cancer)
4 - high public health risk - failed blood donor screening (HIV diagnosis)
classification of non diagnostic medical devices
invasive - contacts the surface of the eye or penetrates the body - surgical gloves, dental cement
non-invasive - contacts injured skin - gauze bandages
active devices - require an energy source - CT or X ray machine, electric tooth brush, hearing aid
special rules - disinfection or sterilization devices
novel food agency
health products and food branch
novel foods
products which have never been used as food, result from a process which has not previously been used for food, or have been manipulated by GMOs
genetically modified crops which may pose an environmental risk are regulated by
the canada food inspection agency
when is a notice of proposal administred regarding to food additives
Health canada will administer a notice of proposal to the public if a new additive is being considered for approval
T/F manufacturers must now list colour additives by their specific common name
true
Hazard
the inherent ability of a substance to cause an adverse effect under defined conditions of exposure
risk
the product of the likelihood of an event and the consequences of an event
- numerical value 0-1
- exposure x effect/hazard = risk
factors which impact risk perception
perceived control
previous experiences
bounded rationality (you make assumptions based on the limited information you have and assume it is good enough)
family concerns
analytical ways of thinking (are you more concerned with numbers)
elements of risk assesment
hazard identification
risk analysis and evaluation
risk control
hazard identification
consider what is known about the hazard (mechanism of action) and how confident you are in what you know (quality and quantity of data)
exposure assesment
identifying key populations (usually children and the elderly), routes of exposure, degree of exposure, where the most significant sources of exposure are if there are multiple
retrospective risk assessment is more common when assessing
pesticides
effect assesment
defining the threshold of exposure above which the tested substance will cause adverse effects - done using animal models most often
equation for defining the Reference dosei
NOAEL x uncertainty factors x modifying factors
what are uncertainty factors
multiples of ten which speak to the degree of uncertainty about the results of a study/risk assesment - for example if you have to extrapolate data from a long term animal study due to a lack of human data you add an UF so your NOAEL is multiplied by 10
how is risk characertization done for noncarcinogens
Hazard quotient = MDD / RfD
if the HQ is equal or less than 0.2 it is negligible
if the HQ is equal to or less than 1, we say there are no adverse effects expected
1-10 = some potential risks are expected and you should reassess
over 10 there are increased potential health risks and you should implement risk management measures
how is risk characertization done for Carcinogens
LADD (lifetime average daily dose) x SF (cancer slope factor)
10 ^-6 is acceptable or insignificant
10^-6 - 10^-4 is potentially risky
10^-4 and up is significant
when there is exposure to more than one risk you combine them additively
major sources of uncertainty
the studies were only observational
you had to extrapolate data from animals to humans or from high dose exposures to low dose exposures
interindividual variability
what is the timeline of CEPA 1999
replaced CEPA 1988, amendments made in 2018, more amendments made in 2023
what is CEPA 1999’s main goal
contribute to sustainable development
what does CEPA stand for
Canadian Environmental Protection Act
what were the calls for revisions to CEPA in 2017
better protect vulnerable populations
focus on high concern chemicals
updates concerning air quality
amendments to cepa introduced in 2021/passed in 2023
every canadian has the right to a healthy environment, fracking and tailings are areas of concern
9 principles of CEPA
- sustainable development
- pollution prevention
- virtual elimination (of persistant bioaccumulative toxins)
- ecosystem approach (opposed to political borders)
- precautionary principle
- intergovernmental cooperation
- national standards
- polluter pays principle
- science based decision making
what is the definition of a CEPA toxin
- immediate or long term harmful effect on the environment and biodiversity
- danger to the environment on which life depends
- danger to human life or health
CCMP
canada’s chemical management plan - introduced 2006 - perform risk assessments on chemicals introduced prior to 1994 and categorize them as harmful or not and implement risk management measures
timing of the phases of CCMP
2006 initiation
2011 a whole bunch of more chemicals added
2016 - now is ongoing
malluscicides
kills snails and slugs
acaricides
kills mites
of the total land area of crops in canada ____ percent are treated with herbicides
84%
examples of intentional pesticide exposure
public hygeine, vector control, human and veterinary medicine
PMRA
pest management regulatory agency
- the federal agency for the regulation of pesticides in canada
what act does the pest management regulatory agency work under/ enforce
pest control products act (PCPA)
primary mandate of the PMRA
prevent unacceptable risks to humans and to the environment
secondary mandates of the PMRA
support sustainable development in agriculture
encourage the use of lower risk products and strategies for pest management
minimize health and environmental risks
increase public awareness of regulatory process
during the pesticide registration process, the PMRA will review
risk to humans, environment and the effictiveness of the productt
timeframe of the pesticide registration process
initial product chemistry and efficacy screening - 4-5 years
researching toxicology - 3-4 years
regulatory evaluation - 1-2 years
PCPA
pest control products act - federal law controlling the import, sale, manufacture, and use of pesticides in Canada - reformed in 2002
the PCPA was reformed in 2002 with these new objectives being added
- strengthen environmental and human protection - safety factors for vulnerable groups, aggregating exposures, encouraging the registration of only low risk and USEFUL pesticides
- make the registration system more transparent - allow public consults, make givernemnts share and make agencies show PMRA their data
- strengthen post registration control - required incident reporting, re-eval old pesticides every 15 years, precautionary principle
6 categories of incidents involving pesticides
humans, domestic animal, environment (lawn damage), food residues, packaging failure, scientific study
domestic animal is most common, then human, then environment
what are the four (five) divisions of the pest management regulatory agency
pre-review screening: make sure submission are in the right format and have paid the fees
human health
environment assessment
laboratory services - evaluate product chem data - is the product what it says it should be
value and efficacy assessments - does the product do what it says it should when used according to the label and is this meaningful enough to warrant it’s approval
human health division of PMRA consists of
tox evaluations - determines the ADI - how bad is the product
occupational exposure assessment - determine the margins of exposure (MOEs) - how much pesticide exposure can occur in a given day
food residue exposure assesment - how much pesticide exposure through our food and drink - set the MRL (maximum residue limit)
margin of exposure (MOEs)
NOAEL / Predicted dose
two components of the environmental assessment branch of the PMRA
chemistry and fate - what happens to the pesticide - make recommendations to limit risk
toxicology - how toxic is the pesticide to all non-human organisms - determine the NOEC - no observed effect concentrations
what is the end point for acute studies of pesticide toxicity
determine lethality dose
what are the goals for short term toxicity studies
determine the effects of repeated exposure over a short period of time - determine its mechanism and target organs - determine dose for long term studies
goal of long term study
fine the NOAEL
which type of human health acute studies are required for pesticides
oral, dermal, inhalation, primary irritation (eye and dermal), dermal sensitization
environmental fate studies base their conclusions on the following four types of data
physical and chemical properties of the pesticide (water solubility, Kow)
transformation process - what might the pesticide transform into as it is degraded (under environmental conditions like the sun)
mobility studies - done in lab - can ground use pesticides move through soils and end up in water
field studies - required in Canada - substantiate lab mobility studies and learn more about persistence and mobility
TGAI
technical grade active ingredient
EP
end-use product
acute studies focus on both _____ in examining pesticides for human health
technical grade active ingredient and end-use product
short term pesticide studies requried:
rodents (oral and dermal) and non rodents (oral)- TGAI -
required longterm studies for pesticides
find NOAEL - rodents - oral - TGAI - chronic and oncogenicity
required special studies for pesticides and human health
should do oral studies on the TGAI for multigenerational reproductive and development, teratogenicity, metabolism and toxicokinetics
required terrestrial invertebrate study
only earth worm acute toxicity, but pollinator studies are more common too because of their importance
required aquatic studies
daphnia - acute and chronic (freshwater invertebrate)
no marine studies required across Canada
acute studies for both cold and warm water fish
wild bird required studies
dietary acute oral quail and duck
required plant studies
freshwater algae, terrestrial and aquatic vascular plants
which type of studies can determine NOEAL
chronic and special studies
two main safety factor (extrapolations) for pesticide human risk assesment
- extrapolate from animals to human (interspecies variation)
- variation within human population
results in reference dose = NOAEL / 100 (ten x ten)
how do we determine if a reference dose is reasonable?
the reference dose (acceptable daily intake) cannot be lower than the estimated daily exposure (you cannot be estimated to be exposed to more of a chemical than is considered acceptable - reference dose)
difference between ADI and acceptable reference dose
ADI is the amount of a pesticide that is considered safe for humans to consume each day for an entire lifetime
ARfD is the dose which a person could be exposed to on any given day and expect no adverse health effects
cancer risk assessment for pesticides
estimates the probability of cancer being caused by an average daily life time exposure - lifetime risk of less than one in a million is considered acceptable for the general population through exposure to pesticide residues
quantitative risk assessment for environment
ratio the highest no observed effect conc (NOEC) to the expected environmental conc (EEC) of the most sensitive species in that relevant area
if the ratio is larger than one, there is a sufficiently large margin of safety and no risk
