DCHAS-L Archives, Jan 29 2022 - Re: [DCHAS-L] Chemical exposure and toxicity

Good point, Peter. We often think cancer tests and other chronic tests have at least been done on medications. FDA only "recommends" this but there is no law requiring it. Most of the medications on the market are not tested for their ability to cause cancer or other chronic effect that are outside of the scope of the medicine's primary interactions.

I had taken hydrochlorothiazide for about 30 years when it was listed in 2013 as an IARC Group 2B carcinogen with both animal and human data. It's a good drug for the purpose, but I think the cancer risk should be part of the individual's personal risk assessment.

Monona

-----Original Message-----
From: Reinhardt, Peter <peter.reinhardt**At_Symbol_Here**YALE.EDU>
To: DCHAS-L**At_Symbol_Here**Princeton.EDU
Sent: Fri, Jan 28, 2022 6:24 pm
Subject: Re: [DCHAS-L] Chemical exposure and toxicity

LD50 data is most common, but that is only only a very limited aspect of toxicity. Very few chemicals in commerce have been adequately tested for hepatotoxicity, neurotoxicity, learning impairment, the many types of reproductive toxicity, etc. Recently, we've learned new things about the toxicity of aspirin. There's so much we don't know about the toxicity of chemicals. - Pete Reinhardt

On Jan 28, 2022, at 3:28 PM, Info <info**At_Symbol_Here**ilpi.com> wrote:

As of 2021, the European Chemicals Agency (ECHA) has registered 22,818 substances from 15,718 companies in 100,679 registrations under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. This document contains further details and also notes that ethanol is the top-registered product with 701 registrations: https://echa.europa.eu/documents/10162/2741157/registration_statistics_en.pdf

General info on REACH here: http://www.ilpi.com/msds/ref/reach.html and https://en.wikipedia.org/wiki/Registration,_Evaluation,_Authorisation_and_Restriction_of_Chemicals

I think that puts an absolute bottom limit on the active # used in the US. I would imagine that it's substantially more given the laxer regulation in the US in addition to trade secret claims, so I would take the ACC's claim as a baseline.

RTECS is now up to 194,821 substances from 3,874 sources: https://www.3ds.com/support/news/single/t86-2021-notification-regarding-biovia-rtecs-20213/

The number of substance used in commerce has recently been estimated as more than 350,000. The authors note "A noteworthy finding is that the identities of many chemicals remain publicly unknown because they are claimed as confidential (over 50=E2=80-000) or ambiguously described (up to 70=E2=80-000)" https://pubs.acs.org/doi/abs/10.1021/acs.est.9b06379

An earlier competing analysis estimated between 40,000 and 60,000 in commerce with more than 99% of the volume being just 6,000 chemicals: https://journals.sagepub.com/doi/10.1177/0748233719893198 However, the authors of that appear to be affiliated with ACC: https://icca-chem.org/news/how-do-we-calculate-the-number-of-chemicals-in-use-around-the-globe/

So, regardless. whether it''s 40,000 or 350,000, I would imagine that few of the toxicity analyses are comprehensive or complete (except for the IARC), and that far fewer have ever been double checked or replicated. So really, the question boils down to what a "small percentage" means in that first statement. Is it a half a percent or 4-5% or 20%? Given the wide margin of error of these competing estimates for the # of chemicals, then I think "small" is indeed an apt descriptor. "Few" might been even more appropriate, but I defer to the toxicologists (and Monona=E2=80™s encyclopedic wisdom) for that.

Rob Toreki

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On Jan 28, 2022, at 2:30 PM, David C. Finster <dfinster**At_Symbol_Here**WITTENBERG.EDU> wrote:

Listers,

I wish to assess the veracity of the statement: "There are many tens of thousands of chemicals in use, but only a small percentage have been tested for toxicity. "

Some numbers: The National Toxicology Program (NTP) states (in 2012) "More than 80,000 chemicals are registered for use in the United States.: (National Toxicology Program | HHS | Catalog of Environmental Programs 2012 (epa.gov)), and that about 2000 more are introduced each year.   The American Chemistry Council challenges this number and says it should be closer to 38,304 due to duplication and inclusion of chemicals no longer being used. (Debunking the Myths: Are there really 84,000 chemicals? (chemicalsafetyfacts.org)) Further they suggest that the EPA Chemical Data Reporting (CDR) is a better measure and that lists "only" 8707 chemicals.

With regard to "toxicity" the IARC has listed 121 chemicals as known carcinogens (although this, of course, is not the only form of "toxicity" that affect humans.)   RTECS (What is the Registry of Toxic Effects of Chemical Substances? - Definition from Safeopedia ) tallies 150,000 chemicals in the list formerly known as the "Toxic Substances List". Their methodology suggests that some "toxicity" testing has occurred the chemical on this list but there is no connection to the NTP list.

Using these numbers in various combinations, one could conclude that the phrase "small percentage" is the original quote above is "pretty fair" or "entirely unfair".   Complex situations often should not be reduced to a single statement and, at the very least, if the original quote is accurate it should be accompanied by some explanations.

I would welcome from the group some insights about a "fair" statement about "chemical exposure" and the degree to which we have determined the toxicity within that group.

I will end with Monona's title from her book:  Pick Your Poison: How Our Mad Dash to Chemical Utopia is Making Lab Rats of Us All.

Dave

David C. Finster
Professor Emeritus, Department of Chemistry
Wittenberg University

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I will end with Monona's title from her book: Pick Your Poison: How Our Mad Dash to Chemical Utopia is Making Lab Rats of Us All.