GENTECH archive


Re: New Novartis Patent

> In the discussion of the Novartis patent, Rick wrote:
> "By the way, the data on imidacloprid (a product of Bayer) and (a product of
> Novartis) indicates that both are much safer to humans and the environment
> than many of the carbamate and organophosphate insectides they replace."
> Estimations of relative safety of chemicals are usually problematic when
> comparing chemicals with different mechanisms of action.  If the mechanism of
> action is the same, then accurate ED50s ("effective doses") can be used to
> compare
> the 2 chemicals' abilities to produce any particular effect, using identical
> test protocols.
> The result is a valid comparison of potencies, that is, a determination of which
>  chemical
> is more toxic (or "safer") for any given dose.
> When mechanisms of action are different, then comparisons of true toxic potency
> are
> not possible.  Imidacloprid appears to be an inhibitor  of nicotinic receptors,
> while
> carbamates and organophosphases inhibit  acetylcholinesterase.
> So, which is "better"?  Quite rightly, people want to identify pesticides which
> will produce
> the least safety problems for farm workers, or the fewest environmental problems
>  like
> soil buildup or effects on non-target wildlife. LD50s are a very crude  measure
> of toxicity,
> and are sometimes used as a  general idex of safety  for chemicals with
> different
> mechanisms of action.  But this use can be misleading.
> Chemicals with different mechanisms of action often have different target organs
>  and usually
> have different side effects.  Thus a useful comparison as to toxicity or
> "safety" requires
> specifying what areas of safety (worker protection, non-target toxicity) are
> most important and
> requires a review of  all the properties of each chemical. Such a review
> ususally indicates
> that comparing 2 chemicals with different mechanisms is the classic
> apples-and-oranges
> problem.
> This is a good example.  If you just look at LD50s , imidacloprid looks "safer"
> than most
> OPs and carbamates.  But imidacloprid appears to have some endocrine effects
> which are
> not found in carbamates and OPs. For example, in short-term feeding  studies in
> rats, high
> doses produced thyroid lesions,  and when rats were fed the chemical for 2
> years, there
> were thyroid  lesions in males at  much lower doses - 300 ppm  (47 mg/kg) and
> females
> at 900 ppm (68 mg/kg).
> So, while imidacloprid might at first look better for worker safety than OPs,
> (i.e., possibly less
> acutely toxic to the central nervous system than OPs or carbamates based on
> LD50s),  the
> potential for chronic endocrine effects at moderate doses suggests once again,
> that safety is
> relative.