Principles of Toxicology 3

Question 0

define HAZARD:

Answer 0

is the intrinsic potential of a chemical to cause harm

- it is a qualitative expression

Question 1

what is toxicity equal to ?

Answer 1

= f(chemistry) x f(biology) x exposure
chemistry= structure
biology- of exposed organism
the extent of exposure

Question 2

define: RISK

Answer 2

is the probability that harm will occur under defined conditions
- often able to quantify risk and manage it

Question 3

what is risk equal to ?

Answer 3

= hazard x exposure

Question 4

what is the purpose of risk assessments ?

Answer 4

reduces the probability of harm which will occur in the environment

Question 5

what is an example used to differentiate between hazard and risk ?

Answer 5

botulinus toxin
- it is one of the most potent toxins known so the hazard for it is extremely high however very few people have died from it in the UK because the exposure to it is very unlikely
therefore risk to human health is low

Question 6

why does the assessment of hazard change with time ?

Answer 6

due to more information about the toxicology of a chemical becoming available

Question 7

why does the perception of hazards change with time ?

Answer 7

until the advent of immunization and antibacterial chemotherapy, death from bacteria was a much greater risk to human compared to exposure to toxicants/toxins
whereas now
we have to be aware of the safety of chemicals and physical agents instead of survival
nowadays we take for granted the advances in science and technology which contribute to survival

Question 8

define:RISK ASSESSMENT

Answer 8

the use of scientific data and a clear set of assumptions to define the likely health effects of exposure of individuals or populations to hazardous materials and situations

Question 9

why is the assessment of toxicology risk difficult ?

Answer 9

there are many different variables to consider which contribute to the outcome
often very little information to determine these variables

Question 10

what is the threshold of pathological condition ?

Answer 10

it is the point at which the signs and symptoms of toxicity become apparent

Question 11

what is one of the major problems to determine whether chemical are safe?

Answer 11

major challenge to develop methods to determine their safety

Question 12

when a new chemical is produced what toxicology is known ?

Answer 12

nothing there is complete uncertainty about nature and possible adverse effects
all that is known is that as the exposure increases the probability of toxicity will increase but the nature and incidence of adverse effects are not known

Question 13

what is known about a new chemical ?

Answer 13

its properties are known such as hydrophobicity and acidity so therefore predictions about its toxicity can be made

Question 14

what is in silico/in vitro data ?

Answer 14

in silico methods= predictions based on chemical structure

in vitro tests (ames test) and animal studies are often the starting points for hazard recognition

Question 15

why should in silico/in vitro studies be carried out to determine toxicology ?

Answer 15

to determine target organ

the exposure-toxic response relationship = define the incidence and severity of adverse effects

Question 16

what is the amnes test ?

Answer 16

used to determine whether a chemical is likely to be a mutagen or carcinogen

Question 17

what is level is determined from in silico/in vitro tests ?

Answer 17

an estimate for the no observed adverse effect level (NOAEL)

Question 18

what strategy does the estimate of NOAEL lead to ?

Answer 18

it leads to the RISK MINIMIZATION - this should prevent the adverse effects in man
- a means of illustrating this is by clinical trials

Question 19

what is the NOAEL used to calculate ?

Answer 19

starting dose for phase 1 clinical trials and a dose that would be safe to take as a daily intake as a food additive

Question 20

how is the NOAEL calculated ?

Answer 20

NOAEL for the most sensitive species and the primary toxic effect is divided by a safety factor

Question 21

what is the safety factor normally and why ?

Answer 21

normally 100
based on the assumption that man is 10 times MORE sensitive than the most sensitive animal species and that clearance is 10x SLOWER than in animals

Question 22

what does risk minimization aim to determine and also what does this mean for phase 1 clinical trials ?

Answer 22

aims to determine an appropraite exposure level of a chemical based on animal study data
it means that in phase 1 clinical trials there is a high degree of confidence that the chemical will not cause toxic effects

Question 23

animal data is not sufficient for risk assessments so what happens next ?

Answer 23

need a risk assessment produced from observations in man

therefore to minimize adverse effects quantitative data needs to be obtained from man

Question 24

how is quantitive data about toxicity obtained from man ?

Answer 24

clinical trials
epidemiological studies - pattern of health of patients treated with the drug
accidental exposure- often chemicals other than drugs

Question 25

what are the different stages for risk assessment of a potential drug ?

Answer 25

hazard identification- first step- info from in silico, in vitro and animal studies
exposure-response relationships- extrapolation from animal studies and human studies
exposure assessment- estimated exposures, routes of entry an characteristics of population
risk determination and deciding on acceptable risk - risk vs benefits
management of risk - sold over the counter, prescription only and saftey within work place

Question 26

why are toxicologists often interested in the metabolisation speeds of drugs ?

Answer 26

because fast metabolism are often less of a risk if it is the parent metabolite that is more toxic but is more of a risk if the metabolite of the parent drug is more toxic

Question 27

what is the golden rule in risk assessment ?

Answer 27

for the government to enable a drug to be approved it must impose no greater risk on those individuals exposed to it as those authorizing it would tolerate

Question 28

what happens when the NOAEL is difficult to determine ?

Answer 28

a benchmark exposure is determined for a specified effect

- a more vigourous saefty factor is applied- often increased to 1000

Question 29

what is TTC?

Answer 29

threshold of toxicological concern

Question 30

what is the purpose of TTC?

Answer 30

it is impossible to determine the toxicity of all different chemcials
therefore TTC enables an alternative approach based on in silico predictions of numerous toxicological end points like mutagenicity and level of exposure to determine a TTC of groups of chemicals

Question 31

what is an example process of TTC ?

Answer 31

TTC for organophosphate pesticides is 18 micrograms per kg of body weight per day
if intake is less than 18 then its considered not to impose risk but if it is greater a risk assessment is needed based on in vitro and in vivo toxicity tests

Question 32

what should the process of risk evaluation estimate ?

Answer 32

the size of the exposed pop
the intensity of exposure 
the frequency of exposure 
the duration of exposure 
potential routes of entry

Question 33

which groups are likely to be susceptible to toxic effects ?

Answer 33

the young and elderly

recognised that actually the sensitivity to toxic chemicals is genetically determined

Question 34

why can safety no be absolutely determined?

Answer 34

because it is not guaranteed that a chemical will not cause any harm

Question 35

what influences safety ?

Answer 35

economics
politics
public opinion

Question 36

what is the precautionary principle?

Answer 36

its an approach to risk management in which its states that is it better to be safe than sorry
anticipation of dangers and therefore trying to minimise them occuring

Question 37

what is REACH?

Answer 37

registration 
evaluation 
authorisation 
chemicals 
this is a regulatory process for the assessment of the safety of chemicals which is determined by the EU

Question 38

what are the key objectives of REACH?

Answer 38

improve the protection of human health and environment
provide a more transparent system for risk assessment and the control of chemicals
promote non animal testing

Question 39

what are the requirements of reach ?

Answer 39

since 2008 chemicals manufactured in th EU or imported in quantities starting at a tonne have to be registered
- this means there must be adequate information to provide to the EU chemical agency to assess its safety and prove its undergone a responsible risk assessment
if there is a risk about the substance the agency has to provide authorisation for it to made, imported and distrubuted in the EU