A large part of the problem in understanding risk of any pesticide is many studies submitted for registration are not public.  Industry pays for such studies and regulatory agencies are not free to publish the data in any detail.  And a company does not want to give the information to a competitor so it remains private.  None the less a significant amount of summary information is often available if you dig far enough.  Here is a fairly detailed description of mammalian absorption and metabolism of Imidacloprid for instance:

http://www.cdpr.ca.gov/docs/risk/rcd/imidacloprid.pdf

The interesting stuff starts on page 14.

A brief summary of how agencies establish pesticide uses from a human consumer safety standpoint is probably in order as if you have not worked in the area this whole topic seems like black magic.

First a no effect level must be established, usually in mice, rats and dogs.  This is done in long term feeding studies where the test substance is incorporated in the diet.  These studies involve whole life studies in mice, three generation reproductive studies in mice and two year feeding studies in rats and dogs as I recall.  So, for the sake of illustration lets say I have run such studies and shown that 1ppm in feed produces no effect.  But some higher dose, say 5 ppm does cause some kind of measurable effect.  That sets the no effect level at 1ppm and humans are assumed to be equally sensitive.

The US EPA then says that is not safe enough to expose large numbers of people.  So they divide that no effect level typically by a factor of at least 1000. That 1000 is a fairly old number and I have not worked in the field for quite a few years.  It may be more than that today. I am sure it is not less.   And the no effect levels are actually calculated based on exposure per body weight, not as ppm in the diet.  But to keep the explanation simple l am just going to stick with ppm in the diet.

Next the company wants to register the pesticide on some specific crop.  Lets say it is cabbage.  So, the company treats a test plot of cabbage with an effective dose they intend to put on the product label, grows the cabbage to maturity, harvests the cabbage and takes it to the lab and analyzes for the pesticide as well as pesticide metabolites that have previously been shown to be important from a tox standpoint.  There are ways to estimate how much cabbage people eat per year and the assumption is that 100% of the cabbage they eat will be treated with this substance so based on how much cabbage they eat and what residues are found an intake is calculated.  If this says that cabbage will supply 1ppm divided by 1000 to a persons diet that uses up 100% of the allowable daily intake and agencies will not consider use of this material on any other crop.  In fact they are likely not even going to register it for cabbage.  The fear is some sub-population may
 eat way more cabbage than average and thus be over exposed.  But, if the residue studies show that only 1% of 1ppm divided by 1000 is going to come from cabbage it is registerable.  Next the company goes thru the same thing for sweet corn, tomatoes, green beans, etc as they view other possible markets.  In all cases each crop must be tested for residue.  Typically such residue studies are done at multiple growing locations so a variety of growing conditions are covered.  Once the sum of the crops on the label gets up to anyplace close to 100% of allowable daily intake no further crops will be registered.

Now, note the safety factors.
1.  A no effect level is established in several species.  No effect means exactly that.  Normal growth rate, normal life expectancy, no induced allergies, no tumors or damage to the various organs based on histology and normal reproduction.  Typically a compound that causes cancer at any exposure level in any test animal is not registerable unless that animal can be shown to have a unique metabolic pathway that does not exist in humans that is the cause of the cancer.
2.  A safety factor of at least 1000 is applied to that determined no effect level.  Sometimes even more than 1000.
3.  The assumption is 100% of any labeled crop will be treated with this chemical even if 100% market penetration never happens in practice.  Still, for some consumer 100% of what he buys could be treated.
4.  Those residue studies are performed on the raw food.  Cooking and processing often reduce residue levels.  But the assumption is some people eat them without any processing so testing is done on the worst case.
5. There are also tests required for birds and non target insects.  You simply are not allowed to kill birds.  But insecticides are going to kill most bugs.  That includes honey bees and native pollinators.  Things like label restrictions (do not spray during bloom periods for instance) are hoped to solve most important non target problems.  But these do not get the attention that consumer safety gets.

Is this system perfect?  Probably not.  It has evolved and changed greatly over the last 40+ years due to new knowledge and I would expect it to continue to evolve.  A fair number of the changes came from suggestions industry made.  I was personally involved in one such change that the US EPA said was impossible but we felt was possible and demonstrated we could do it.  I personally feel it is considerably more likely that some pill my doctor tells me to take will hurt me than I am likely to be hurt by some pesticide residue I get from food I buy at the grocery store.  As I have been harmed by such pills I have grounds to feel that way.  It is a fact we have more people die from tylenol in the US every year than from pesticide poisoning from food.  The only food related pesticide induced deaths I can recall off hand in the last forty years were due to off label and thus illegal pesticide use.

Please remember that my explanation above is simplified greatly to fit an email.  A detailed description would take a book.  It took me six months as a project manager on a developmental compound I knew I was going to kill to work out the critical development path.  Shortly after I finished the critical path on paper I killed the project.  I told my boss when he asked me to take the job of project manager I would kill it so he should pick someone else.  He said "You have to do what you have to do."

Dick

" Any discovery made by the human mind can be explained in its essentials to the curious learner."  Professor Benjamin Schumacher talking about teaching quantum mechanics to non scientists.   "For every complex problem there is a solution which is simple, neat and wrong."  H. L. Mencken

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