Chemical Risk Assessment & Environmental Consultancy

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Demonizing human pharmaceuticals is an inappropriate therapy resulting from a flawed diagnosis.

David Taylor - wca environment

SETAC PAG Workshop – Basel May 2014 Slide 2

Advances in analytical science enable us to see residues of pharmaceuticals in the environment that used to be invisible.» Most are <1 µg l-1, many are <0.1 µg l-1, Drinking Water <0.01 µg l-1

The principle source of most pharmaceuticals to the environment is from the excretion products of patients.

At the levels currently present in the environment:» Risks to human health are considered to be very unlikely» Acute effects on aquatic life are considered to be insignificant» Data on the potential long term impacts is increasing, and

varied, however some significant impacts on some aquatic life forms cannot be ruled out.

What do we now know about Pharmaceuticals in the Environment?

N J Ayscough, J Fawell, G Franklin and W Young 2000Environment Agency R&D Technical Report P390Review of Human Pharmaceuticals in the Environment

SETAC PAG Workshop – Basel May 2014 Slide 3

Plasticisers

Pesticides Biocides

Flame Retardants

Fragrances

Personal Care Products

Detergents

PAHsPCBs

Perfluorooctanes

BPA

PharmaceuticalsPharmaceuticals

We are suffering from tunnel vision

SETAC PAG Workshop – Basel May 2014 Slide 4

The Challenge of Emerging Pollutants

The number of substances that we couldn’t previously see but can now detect is increasing exponentially.

Presence is not

synonymous with harm

SETAC PAG Workshop – Basel May 2014 Slide 5

Advances in Analytical Science

Decade Detection Limit Ratio Description

1900s 1 gram / litre (0.1%) 1 in 103 Parts per thousand

1930s 1 milligram / litre 1 in 106 Parts per million

1960s 1 microgram / litre 1 in 109 Parts per billion

1980s 1 nanogram / litre 1 in 1012 Parts per trillion

1990s 1 picogram / litre 1 in 1015 Parts per quadrillion

2010s 1 f emtogram / litre 1 in 1018 Parts per quintillion

???? 100 molecules / litre 1 in 1021

???? 1 molecule / litre 1 in 1023

With a big enough sample analytical chemists can

now find anything, anywhere if they look hard enough.

SETAC PAG Workshop – Basel May 2014 Slide 6

What defines a pharmaceutical?

Pharmaceuticals cannot be defined by any of

their chemical, physical, structural or biological

properties

A pharmaceutical is simply any substance

that is used for a pharmaceutical purpose.

SETAC PAG Workshop – Basel May 2014 Slide 7

Pharmaceuticals in the environment: The ‘Problem’ in perspective Taylor & Senac (2014) [Doi: 10.1016/j.chemosphere.2014.01.011]

Pharmaceuticals can only be differentiated from other substances as a consequence of their use.

Pharmaceuticals are ‘discovered’ not designed ab initio Compared to other micropollutants pharmaceuticals are:

o Neither more widely distributed nor found at higher concentrationso Not more prone to mixture, metabolite or endocrine disruption effectso Not necessarily more biologically active.

– Likely to be less toxic and accumulative in mammals

There is thus no reason to treat the pharmaceutical group differently to other groups of micropollutants

o However individual pharmaceuticals, like any other micropollutant, might be of environmental significance e.g. Ethinylestradiol fish feminisation & diclofenac on Asian vultures.

SETAC PAG Workshop – Basel May 2014 Slide 8

Pharmaceuticals are data rich substances and are getting richer

More information is probably available on the toxicology of pharmaceuticals than all other substances put together

Data on toxicology (including mutagenicity, carcinogenicity,

cytotoxicity, histopathology, teratogenicity …), kinetics,

metabolism, mode of action… for humans AND animals.

SETAC PAG Workshop – Basel May 2014 Slide 9

Faulty diagnosis can produce inappropriate therapies

SETAC PAG Workshop – Basel May 2014 Slide 10

Beware the Policy Syllogism

“Something must be done!,

This is something,

Therefore we must do this”

Actions need to address actual problems and be proportionate

BBC “Yes Minister” 1988

SETAC PAG Workshop – Basel May 2014 Slide 11

Pharmaceuticals in Drinking WaterRisk to Human Consumers in Perspective

SETAC PAG Workshop – Basel May 2014 Slide 12

TREATED SEWAGE DISCOVERED IN OUR DRINKING WATER

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SETAC PAG Workshop – Basel May 2014 Slide 13

Any additional treatment technology should be aimed at the global reduction of ALL those micropollutants which indicate significant

environmental risk, not just pharmaceuticals

Removal of pharmaceuticals in wastewaterAn expensive way to solve the wrong problem

SETAC PAG Workshop – Basel May 2014 Slide 14

What does the industry need to do?

Minimise Environmental Exposure» Ensure discharges of pharmaceuticals from

manufacturing are controlled.» Optimise drug use by patients» Actively promote and facilitate the safe

disposal of life expired & unused pharmaceuticals.

Improve Understanding of Environmental Impact» Publish ERAs for all existing pharmaceuticals.» Establish active ecopharmacovigilance programmes.» Continue to support research into the ecotoxicological

effects of chronic exposure to pharmaceuticals.

SETAC PAG Workshop – Basel May 2014 Slide 15

The societal risk benefit balance is very different for pharmaceuticals

Society will usually tolerate a higher level of risk to man & the environment to gain significant patient benefit.

Risk benefit assessment of pharmaceuticals is complex.» Not all side effects will be known when the product is approved.

o Pharmacovigilance is used to update the assessment» Trade offs will need to be made between + ve and – ve aspects.» A balance will be needed between benefit and uncertainties.

Pharmaceuticals receive a comprehensive in depth risk benefit evaluation before they receive a marketing authorisation.

A single regulator is needed to balance ALL the evidence.» Authorised use of the drug may result in damage to the environment

SETAC PAG Workshop – Basel May 2014 Slide 16

Some degradation of the natural environment may be an acceptable price to pay

for significant human benefit

Another Inconvenient TruthApologies to President Gore

This has been socially acceptable since time immemorial(We just don’t like to admit it)

SETAC PAG Workshop – Basel May 2014 Slide 17

SOCIALLY ACCEPTABLE AREAS OF VERY POORECOLOGICAL QUALITY

SETAC PAG Workshop – Basel May 2014 Slide 18

SOCIALLY ACCEPTABLE AREAS OF EXTREME BIOLOGICAL IMPACT

SETAC PAG Workshop – Basel May 2014 Slide 19

Conflict with the EU Water Framework Directive

Regulatory Approval for Marketing Authorisation of an NME is based on a difficult balance of risks and benefits.» Consequently pharmaceuticals are exempt from a lot of legislation to

avoid conflicting decisions being taken by different regulators.o e.g. Art 2.5a of REACH provides an exclusion for medicinal products.o Note Art 68 of REACH provides a reserve power for the Commission

There is no exemption in the EU Water Framework Directive» ALL waters to be of “good ecological quality”» This is already causing problems as one regulator seeks to eliminate

potential environmental damage that a different regulator is prepared to tolerate.

SETAC PAG Workshop – Basel May 2014 Slide 20

Potential consequences of requiring compliance with WFD Quality Standards

End of pipe treatment» Upgrading effluent & water treatment plants is costly & uses energy.

o Estimated cost to remove Ethinylestradiol in the UK was €M36,000o Selective targeting of ‘hot spots’ might limit costs.

Source control (Restriction of drug availability)» Reduced number of ‘over the counter’ (OTC) drugs available.

o e.g. Ibuprofen & Diclofenac could revert to prescription only.o Increases GP consultations & increases health care costs.

» Replacement of old generics with newer products.o Spreads total drug load across more compoundso Increases health care costs.

» “Improved” prescribingo More rigorous prescribing of antibioticso 2% drop in ethinylestradiol input by not prescribing to girls below age of consent

SETAC PAG Workshop – Basel May 2014 Slide 21

Conclusions

Pharmaceuticals as a group are no more of a problem than any other micropollutant ‘group’.

Individual pharmaceuticals may pose specific problems but these should be dealt with on a case by case basis.» Antibiotics may be a special case

A satisfactory ERA is needed for all micropollutants including all existing pharmaceuticals.

A proportionate ‘no-regrets’ approach should be applied to reducing inputs of all micropollutants to the environment including pharmaceuticals.

Faulty problem diagnosis can lead to inappropriate actions, unhelpful regulatory conflicts and aggrieved citizens.

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