Category Archives: APVMA – Regulation of Ag & Vet Chemicals in Australia

Australian pesticide regulator’s ‘Risk Analysis Framework’ – does it provide transparency to the risk assessment process?

The Australian Pesticides and Veterinary Medicines Authority (APVMA) published a draft Risk Analysis Framework in November 2011 (see http://www.apvma.gov.au/consultation/public/2012/risk_analysis_framework.php). While publication of the Risk Analysis Framework should improve transparency about the way decisions are made within APVMA and should help all stakeholders to understand what data the regulator needs to enable it to make its decisions, lack of clarity within the Framework results in the document failing to clarify what data are required by the regulator.

An example of the lack of clarity in the draft Risk Assessment Framework is the statement that toxicology data are assessed to determine ‘if possible, a “safe” level of exposure in animals.  This is known as the no-observed effect level (NOEL)’.  The Framework also claims that ‘international best practice’ is used for risk assessments.

The Framework, as published leads me to ask if the APVMA really means it uses international best practice or does it really require the use of practices (such as the NOEL) that have been largely abandoned by other regulators?  Without clarity, an applicant cannot decide whether data relied upon by other regulators to approve substances will be be usable by APVMA to assess the risk posed by a substance or not.

The issue of the NOEL is not the only instance of a lack of clarity within the Framework.  But it is an important example.  So what is wrong with the NOEL?

The NOEL theoretically looks at any observed effect.  The NOEL is the dose at which the administered substance causes no effects, irrespective of whether the effects are adverse or not.  Some effects may have no real significance and are not used for regulatory decision-making.  For this reason, the NOAEL or No Observed Adverse Effect Level is now more commonly used for such decision-making.

Consider this example.  Ivan Petrovich Pavlov once did experiments in which he rang a bell when dogs were to get food.  Eventually, the dogs would start to drool whenever the bell was struck (because they associated the bell with food).  We know drooling, or salivation, is an important response to food.  It starts the digestive process.  However, it would not normally be considered an adverse effect — but it is an effect.

Assume if, instead of striking a bell, Pavlov sprayed some chemical into the air.  The animals might start drooling every time they smelt the chemical, expecting food to be served.  Would we consider drooling in this case to be the type of effect that should drive regulatory decision making, i.e. determine if the chemical is allowed to be sold or not?  Should we say a chemical is not allowed to be sold or used because it causes drooling in this experiment?

If the regulator requires the dose or concentration at which No Effects are observed to be used for regulatory decision making,  the drooling would have to be considered an effect and would need to be used as the basis for decisions such as whether a chemical can be supplied or not.  In this case, to select a  “safe” level for the chemical, as defined by the regulator, we would need to look for a concentration of the chemical that does not cause drooling.  The highest rate or concentration of the chemical tested that does not induce drooling would be termed the NOEL.

In contrast, the NOAEL would recognise drooling is an effect but not an effect that is significant in relation to regulatory decision-making.  Decisions about whether to permit supply or use of the chemical would need  to be made on adverse effects.

What effects are “adverse” is something that competent toxicologists must determine.  The NOAEL is the highest dose tested that did not produce any toxicologically significant effects, as determined by the expert toxicologists.  APVMA has access to highly competent toxicologists (and other experts).  However, the Framework, as written, could reduce the ability of these experts to use their expertise in regulatory decision making.

Some people may argue no competent regulator would make a decision simply because, say, an animal started to drool because of some odour.  This may be true but we know regulators are not always the final decision makers, e.g. legal action may result in courts requiring a strict interpretation of terms used in the Framework.

To avoid problems in the future, I believe it is essential that the Framework use  precise terminology.

On the other hand, if APVMA really does not want experts to have the flexibility to use their expertise in decision making, and does require them to use the NOEL rather than the NOAEL or other appropriate criteria, then APVMA should not mislead stakeholders by claiming it uses ‘international best practice’.

In my view, the Risk Analysis Framework must be amended to ensure there is clarity as to what is expected.  Only then will the regulated community, the regulator and other stakeholders have common ground for determining what is and what is not acceptable.

 

What have we learned in the last 100 years about poisons?

Over the last 100 years our knowledge of “poisons” has increased dramatically.  We can look back now at some of the products used in the early 20th Century and we ask how could anybody have been so stupid.  What have we learned from these early experiences?

I recently read “The Poisoners Handbook” by Deborah Blum (Penguin Books).  The book describes use of poisons for murder in the early 20th Century in the US but also gives an excellent insight into some of the issues of the time.  Reading the book made me think about the implications for pesticides today.

Here are some interesting facts from Blum’s book:

  1. Prohibition increased the number of people affected by methanol poisoning.  Unlike ethanol (“drinking alcohol” or food grade alcohol), methanol is toxic — it is converted to toxins in the body e.g. formaldehyde.  People selling alcohol illegally in the US during Prohibition often substituted cheaper methanol for food quality alcohols.
  2. In the mid-19th Century people would drink mercury believing it would cure constipation.
  3. Mercuric chloride was sold as a pesticide (to control bedbugs) as well as being an ingredient in laxatives, antiseptics and diuretics.  Doctors prescribed mercuric chloride for chronic bacterial infections.  The substance is corrosive to eyes, skin and the digestive tract and today, the IPCS Inchem datasheet for mercuric chloride states “Avoid all contact!”
  4. Tetraethyl lead was found to cure knocking in car engines.  Workers in the Standard Oil plant making the substance were observed to have become “a little odd”.  They would become lost in plant grounds.  They had troubling remembering friends and eventually, they started collapsing, convulsing and “babbling deliriously”.  Standard Oil’s response was “these men probably went insane because they worked too hard”.  Apparently, the company “didn’t see a problem” other than for the workers working themselves to death.
  5. Radium was used in consumer products including radium water (to make the “drinker sparkle with energy”), radium soda, radium candy, radium based facial creams (to rejuvenate the skin), radium facial powders as well as soaps and pain-relieving preparations.  Marie Curie used to carry a phial of radium in her pocket – she liked to watch the “pretty blue-green light” in the dark.  Marie Curie died from effects attributable to radium.

Some questions that arise from the above:

  1. Prohibition was a failure.  It did more harm than good.  Is the current regulation of pesticides doing more harm than good?
  2. In the 19th Century people did not know the dangers associated with mercury.  That did not stop them from dying from the effects of consuming mercury.  What is it that we do not know about the products we use today?
  3. People, even qualified medical practitioners, were recommending the use of a highly corrosive substance, mercuric chloride.  It was used in cosmetics yet it was known to be corrosive.  Can we blame these people for using what was available at the time, e.g. to cure syphilis?  Today we have safer and more effective products but what were the options then?
  4. People working themselves to death?!?  We can claim Management at Standard Oil was irresponsible but do we not still see similar excuses being made by companies?  Look at tobacco, asbestos.  What do we not know about some of the other products on the market?
  5. Marie Curie believed in her invention.  People did not understand the dangers.  Yet they died as a result of the inherent “qualities” of radium.  What do we need to know to prevent the next big invention killing us?

Regulation is important, but it should not build such high barriers to entry that people find ways around the barriers.  As with prohibition, the alternatives found may pose unacceptable risks.

We also need to be aware that new technologies, such as radium, might come with new risks.  However, we cannot refuse to adopt these new technologies while waiting for safety to be demonstrated – nothing is safe; even water poses unacceptable risks in certain situations.  If alternatives to mercuric chloride were not allowed onto the market, would we still be relying on mercuric chloride to treat chronic bacterial infections?  In the same way, failing to allow new crop protection technologies can force us to continue relying on old technologies.

While we do require regulatory systems that facilitate entry of new technologies, we cannot forget that people may, maliciously or through ignorance, ignore risks posed by these technologies.  It is essential to have an effective regulatory system that minimises the potential for commercial interests to adversely impact the health of people and the environment in general.  But, the system must not build such barriers that those commercial interests find other ways to expose us to their products.  Prohibition failed.  We can learn from that experiment.

North American Governments Facilitate Access to Better Crop Protection Tools

I was fortunate to be able to attend the Biopesticide Registration Improvement Course (BRIC) held 13-15 April 2011 at the US EPA headquarters in Arlington Virginia, USA.

Representatives from US EPA, Canada’s Pest Management Regulatory Agency as well as industry representatives from all NAFTA countries were present.

Full marks to the organisers who pulled together an excellent meeting.

An important point from the meeting was the way the US and Canadian Governments are promoting reduced risk products.  The regulators work with industries to facilitate availability of reduced risk products.

  1. The IR-4 program (http://ir4.rutgers.edu/) provides funds for development of selected prducts.  Furthermore, registration applications submitted by IR-4 are exempt from payment of registration fees to US EPA.
  2. The Canadian Government Pesticide Risk Reduction Program, a joint initiative of Agriculture and Agri-Food Canada and Health Canada’s Pest Management Regulatory Agency (PMRA), works to reduce the risks from pesticides used in the agriculture and the agri-food industry in Canada (http://www4.agr.gc.ca/AAFC-AAC/display-afficher.do?id=1288277891464&lang=eng).
  3. The Canadian Pest Management Centre works to improve access to low-risk, environmentally sustainable and economically competitive pest control tools and practices, including biopesticides  (http://www4.agr.gc.ca/AAFC-AAC/display-afficher.do?id=1288727518132&lang=eng).  Besides providing advice, The Pest Management Centre funds development projects.  It works closely with registrants, PMRA and growers to develop high quality submissions.
  4. Both IR-4 and the Canadian Pest Management Centre work closely with the regulatory authorities in their respective countries.

We can compare this with Australia:

  1. There is no support for registration of niche, reduced risk or other products.
  2. HAL, which attempts to cater to the minor use needs of the horticulture industry runs a program to obtain minor use permits – not registrations.  Only already registered products can be given permits and HAL needs to pay for the permits.

A way to reduce cost of commercialising niche products needs to found.  Options might be:

  1. Reduced data requirements where products have a track record of safe use elsewhere or have been evaluated by another acceptable regulator.
  2. Allow confirmatory efficacy data to be obtained during early commercialising rather than prior to submission for registration.
  3. Greater acceptance of overseas data to support registration in Australia.
  4. Reduced fees for such niche products.

The Australian Government must recognise that Australian agriculture needs access to modern tools.  The world is demanding foods be treated with lowest risk pesticides.  Unless the Government introduces measures that facilitate the registration of low risk, niche products, Australian growers will be excluded from international markets.