Toxicology Case Studies

Question 1

What does Paul Anastas define Green Chemistry as:

Answer 1

“Green Chemisty is the design of chemical products and processes that reduce or eliminate the use and/or generation of hazardous substances to health or the environment”

Question 2

What is Toxicity?

Answer 2

An adverse health effect caused by a chemical

Question 3

What is Toxicology?

Answer 3

The study of how chemicals interfere with the normal function of a biological system to cause an adverse health effect
(particularly human health)

Question 4

Paracelsus is a 15th centry physician and the ‘Father of Toxicology’
What does her say about toxicology?

Answer 4

“All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy”

Question 5

What is ‘LD₅₀’

Answer 5

• The median dose of a material that cases the death of 50% of tested organisms
• When delivered all at one
• (Obviously this cannot be tested for humans)

Question 6

What is ‘LC₅₀’

Answer 6

The median concentration of a material that causes the death of 50% of tested aquatic organisms

Question 7

The higher the LD₅₀ or LC₅₀ of a given material….

Answer 7

…. the less toxic it is

Question 8

Why can we not always use animal data to indicate the toxicity of a compound on other animals or humans?

Answer 8

Sometimes an animals has particular sensitivity to a compound

Question 9

Toxicity is a function of…

Answer 9

Toxicity = f(does, expose, time)
* The real problems are difficulty of testing mixtures of chemicals (because of the number of possible combination)
* Also, chemicals can be transformed in the environment - perhaps resulting in worse effects

Question 10

List some determining factors of Toxicity

Answer 10

• Route of Exposure (oral, dermal, inhalation)
• Dose
• Frequency of exposure
• Duration of exposure (some species can be sick hence reducing the duration)
• Biological properties (age, gender etc)
• Chemical properties

Question 11

What does In vivo mean
(relative toxicity testing)

Answer 11

• In or on a living organism e.g. animal or human
• Animal models have been used for a long time

Question 12

What does In Vitro mean
(relative to toxicity testing)

Answer 12

• Within the confines of a test tube or lab dish
• Became more plausible due to high throughput screening
• Tests individual cells, hence the effect may be seen much more rapdily

Question 13

What does “in situ” mean?

Answer 13

In its original place

Question 14

What does “In silico” mean?

Answer 14

Using computers and computer simulations to predict the effect of chemicals
Toxicity assessments that use computation resources to organise, analyse, model, simulate or predict the toxicity of chemicals

Question 15

Would you use ‘In Silico’ testing on its own?

Answer 15

Probably not
Instead to compliment ‘in vitro’ and ‘in vivo’ toxicity tests to potentially minimise the need for animal testing, reducing the cost/time of toxicity test and improve predictions
Brings a unique advantage of being able to estimate toxicity of chemicals before they have been synthesised

Question 16

In 1921, Thomas Midgley Jr discovered that adding Pb(Et)₄ to petrol is cured ‘knocking’
What long term issues did this have?

Answer 16

• When burned Pb(Et)₄, forms PbO and PbCl₂
• Derek Bryce-Smith campaigned on the effect of environmental lead on children’s IQs
• Took till 2000 for the sale of leaded petrol to be banned in the UK (as he was ignored)
• Lead still spread all across the globe into the Artic

Question 17

What key factors must be considered to Environmental Toxicology?

Answer 17

• Persistence (how long they will last in the environment)
• Bioaccumulation
• Biodegradation
• Biochemical mechanisms/processes of wildlife (how some organsims may be effect more than others)

Question 18

Give an example of a drug which was a cure for one species but a poison for another?

Answer 18

• Diclofenac was a drug used on cows and proved to be sucessful
• However it poisons vultures which feed on dead cows
• Resulted in 99% of the vultures disappearing
• Is now banned

Question 19

What was the Minimata disease?

Answer 19

• Minamata is a costal Japanese town
• where chemical companies discharged Hg residues into the bay for 1932-68
• Bacteria converted these residues into HgMe₂ which bio-accumulated in fish
• Resulted in more than 2,500 people who ate the fish developing neurological symptoms and dying

Question 20

A paper released in 2020 talked about how the Coho Salmon were found to be dying when trying to breed in the urban creeks in the US Pacific Northwest
What was the problem?

Answer 20

• After analysis of over 200 compounds
• 6PPD was found to be the issue, tho not toxic itself
• It is a tyre additive, were when the rubber wears off the tyre additive gets washes out by the rain and runs into the creeks
• It then becomes oxidised by ozone to form 6PPD-quinone which is what was killing the salmon
• The quinone was 100x more toxic than the original 6OOD additive

Question 21

Pollutants like the 6PPD-quinone are detected by which technique?

Answer 21

Mass spec
(can’t run an NMR because not enough sample to run)

Question 22

What is ‘Green Toxicology’

Answer 22

Describes the application of predictive toxicology in the design, manufacture, use and disposal of new materials and chemicals
(aim basically to produce products which are safer for the environment and humans)

Question 23

What are some Key Principles of Green Toxicology?

Answer 23

• Benign-by-desing
• Test-early; produce safe
• Avoid exposure and thus testing needed (no need to test chemical saftey if people are not exposed to them)
• Making testing sustainable

Question 24

Relating toxicology to ionic liquids, what is the issue there?

Answer 24

A problem with ionic liquids is that the toxicity of many of them have not been examined

Question 25

What does Green Toxicology promote?

Answer 25

New techniques to.. * reduce animal testings * the amounts of chemicals used + disposed of during tests * Increased consideration of toxicity in synthesis, use and regulation of chemicals