@bananafish81
I was involved in toxicity testing of various things, so not analgesic specific, but to answer your question about how safety in pregnancy is assessed... sorry for the length everyone!
TRIGGER WARNING - some of this may be disturbing.
The compound will be administered daily to pregnant rats (usually around 90 of them) who have been provided by a regulated supplier who has mated them on set days (they monitor their cycles so they can mate them on the most likely day and then send the ones who have mated). From day 4 of their pregnancy to day 18 or 19 (they have a 21 day pregnancy)
The compound is administered via the intended route, so if it is to be taken orally it's administered orally, if IV it's administered IV, if it's an agrochemical which humans may be accidentally exposed to its mixed in with their food.
There will be a control group who are given the same treatment without the compound, and then three or four 'does levels' with varying amounts given,
They have blood taken to check exposure levels usually on day 6 and 16 or 18, at various time points, they each have as few samples as possible, so some will have a sample taken 30 minutes after admin, some 2 hours, etc. some are sometimes kept sample free, as a control to make sure sampling doesn't confuse the results of the trial, though as blood analysis gets better less blood is needed so this is not often required and means fewer animals can be used.
They are euthanised on day 20 of pregnancy with a rising concentration of carbon dioxide (so they don't notice and sort of just pass out and don't come round), or with an anaesthetic overdose (via injection into their abdomen) - the method depends on the establishment, both are considered humane. Some people don't like using carbon dioxide, but IME if done properly it causes less distress than the anaesthetic in rats.
SECOND TRIGGER WARNING - really, stop now if you're squeamish. SKIP TO NEXT CAPS BIT if you want more info about less triggering stuff.
The deceased female rat is then opened up and the unborn pups removed, they are euthanised individually via anaesthetic overdose and/or rapid cooling.
The female rat is necropsied (like and autopsy but on an animal) in great detail to check for any abnormalities. Tissues are taken to be examined by a pathologist.
The pups are examined externally, then half are necropsied, and half are treated so that their tissues become clear and their bones and cartilage are dyed, so the formation of their skeletal system can be assessed.
OK WORST OVER
All abnormalities are recorded and then the totals compared to background data (obviously sometimes abnormalities occur anyway) and the control animals, to see if there has been any increase.
If the rat trials show the compound to be safe it is then repeated in rabbits. Which is the same protocol but they are always euthanised with an IV administered anaesthetic overdose.
Other trials will also be done where rats are mated while being dosed daily to assess effects in male and female fertility, and studies done where the pups are born after the mothers have been dosed in pregnancy and while lactating to assess the pups development afterwards.
For accidental exposure (so pesticides, etc) multi-generation studies are done where the rats live 3 generations eating treated food to ensure it won't have an effect on future generations of humans.