The response must be at least 100 words and include one of the following:

1. Challenge your peer's way of thinking.

2. Add new information or

3. Ask a solid follow-up question that describes why you're interested in that question.

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"All models are wrong, but some are useful" George Box

The concept of No Observable Adverse Effect Level (NOAEL) has been useful in determining RELATIVE safety in the 20th and 21st centuries. It is the idea that the level at which a substance is given is low enough to be theoretically benign.

However, life is usually more complicated and research suggests that (Tsatsakis et al., 2019) found that exposing rats to a mixture of chemicals below what is considered NOAEL can lead to genotoxic and cytotoxic effects.

While this experiment does not disprove NOAEL as a concept, it forces us to re-evaluate what we mean by the term.

There is room for additive and/or synergistic effects when mixtures are involved. Does it still count as NOAEL if you mix chemicals? And if so, how could you ever hope to experiment with all the different combinations and categorize them?

Should this be the next paradigm of risk assessment research (based off commonly found combinations in human environments?).

Another question is about chronicity. These rats were exposed, frequently and regularly, for 18 months, a consequential portion of their short lives!

Should the definition of NOAEL be dynamic? Accounting for frequency and route of exposure? Can we even use this data and extrapolate in humans reliably? For all we know, some of these 13 chemicals are more (or less) effectively regulated by our more complex biochemistry.

As a good article should, this one raises more questions than it answers, but helps us err forward rather than backwards.