Closure questions on Module 1, 2017

Q. I am aware that testing on animals does not always accurately describe the toxicity towards humans. What are ways to more accurately determine the toxicity?
A. In our tox class, ENVE 652, we mention PBPK modeling.  That is one method of trying to reconcile admiral testing to humans. 
http://www.raperkins.net/ENVE_652/Module14/PBPK/PBPK.htm
But it’s still an estimate.

Q. Does OSHA actually conduct toxicity tests themselves or do they contract with universities or private companies to perform the tests, such as NOEL, EC, etc.  Also, if they do outsource work, do they rely on one institution for dose-response data or do they have a more rigorous acceptance process.  And if they do testing in-house, do they have third party verification?
A. OSHA does have its own labs that can do tox testing, but it is much more common that they are presented some evidence of toxicity to workers at relevant concentrations.  Both labor unions and industry do testing and present evidence to OSHA.  There is testing done in Europe and elsewhere that is published.  Therefore, it is much more common that labor or management will bring an issue to OSHA based on these publications and OSHA will write a rule based on the testing of others, rather than try to do their own testing.  NIOSH does more testing in its laboratories and using contract labs.
Q. Module 1 Question - Do lethal dosages change? I.e. as new research is developed, or accidents happen for that matter, does regulators decrease the dosage recent ages? 
A. Hmmm.  Deep philosophical question.  There can be only one lethal dose per animal, of course.  If you give 100 animals the LD 50 dose, 50 will die.  But what do we mean by “animal?”  Or even “rat?” or even “white rat?”  There several common types of laboratory white rat and each type (usually “strain”) will have slightly different LD 50s.  Even with inbred animals of the same strain, weight, age and so on, it is very common for different labs to report different LD 50s.  There may be different conditions at the lab, or just random variation.  BTW, testing 100 animals would mean testing about 1000.  100 of each sex at 5 different concentrations or doses.  That much testing is almost never done.  So when you read “ The LD 50 of ethanol is…..xx” you’re really looking at an accepted standard, at least accepted by the entity that said it.  If no one challenges it, the standard becomes widely accepted.  Sound awful?  If you are looking for numbers that are  plus or minus 1%, the process is indeed awful. On the other hand, if you are looking or numbers that are plus or minus 25%, the numbers are pretty good.  In general, the LD 50 are a good guide to relative toxicity of compounds. 

Q. A question on submodule 1E. Does the time of exposure to be considered acute or chronic have a specific defined time? For example if exposed to a toxin, regardless what that toxin is or the dose, for more than 96 hours is considered a chronic exposure but for less than 96 hours is considered an acute exposure. I would think that what is considered a chronic vs. acute exposure depends on the specific toxin and the dose (what is the LD50 for that toxin and is the subject going to be dead before 96 hours has passed).
A. In conversation regarding humans we might say that “acute” is exposure for an hour or so, while “chronic” extends of weeks and months.  But for humans under a regulatory matrix we would use much more precise terms, which we will get to soon.  For animal testing, we need to specify exactly how long the animals are exposed.  Here we often talk about “96 hour” tests.  The animals are exposed for 96 hours and effects noted then or at some time following, which also needs definition.  For chronic animal testing, they might be given something in their food for their lifetimes – about two years for rats and mice. 

Q.With regard to dose-response curves, what are key limitations of studying impacts of mixtures of chemicals such as a standardized schedule of the most common pesticide "tank" mixes or combinations of herbicides, fungicides, insecticides mixed together and applied in a singular application?
A.The D-R curve would be for either a single chemical or the mix.  Here is a site about mixtures.  http://www.raperkins.net/ENVE_652/Module09/Submodule9C_Mixtures/9C_Mixtures.htm In many cases the D-R of one chemical is not known, and the effects of the mixture are completely obscure. 

Q.I like your response in the 2013 Closure document for the question regarding defining a hazardous substance, "see if it is on a "list"".  Unfortunately, regulatory authority is sometimes exercised on a definition level out of fear of litigation and negative public perception. 
A. Here is another site you might like:
http://www.raperkins.net/ENVE_652/Module12/12A_RegulatoryTox/12A_RegulatoryTox.htm