system
Given the following post, respond as if you're commenting on Reddit:
human
How do we know a substance is toxic without poisoning someone with it?
gpt
Step 1: Don't use it on a human; first try it on an animal model (an animal that has a physiological response similar to a human, not an animal that gets paid to wear to have photos taken).  For instance, sheep eyeballs are similar enough in size, shape and composition to human eyeballs.  However, dog's will be poisoned by chocolate or grapes but humans are not, so are a bad animal model for toxicity studies.

Step 2: accidental exposure.  Factory worker accidentally spills a substance.  Someone on drugs thinks it's a good idea to shove a substance up their butt for some reason.  "Alternative medicine" and "natural therapy".  Usually you find long term evidence of toxicity from people who spend a lot of time or handle very concentrated substances, such as factory workers or applicators.

Step 3: Crazy hard computer modelling.  You make a fake substance in a software program and bump it against fake biological receptors.  You can see when something fails against some common biological receptors, but you can't test everything so you are really focused on failures and ignore success.  An all-clear *in silico* may still be toxic *in situ*.

Step 4: Drug/exposure trials.  Deliberate incremental dosing experiment on a human, preferably two humans, and step up concentration until bad signs appear.  1 dose today for me, wait and observe.  2 doses for you tomorrow, wait and observe.  This is how Phase 1 drug trials work and why your drug symptoms may include "itchy butt" or "an impending feeling of doom", just because one person experienced that on day 7 of a twelve day exposure test.