Since this is a toxicity study the goal is to use high concentrations to define doses that are actually toxic. So the answer is that it depends on your herbal agent. It might not be toxic or it could be very toxic. You should have data from an acute test before going on to longer term tests. Acute tests will inform your chronic studies. I'm not sure what you mean by mg/kg vs. mg/kg body weight. Aren't these the same? You should also consider how humans would take the herbal compound--will they drink a boiled extract/tea, will they ingest it directly, etc. ? It would be best if the rats were given the herbal material in the same manner that you intend for people to take it, if possible. There are several good books and papers that you can look to for ways to construct your study.

Thanks Prof/Dr Charles Miller, the formulation is actually a poly-herbal drink and there is toxicity study on it yet. So i thought i could give the rats a low dose and high dose like 15ml/kg body weight of rat and 30ml/kg body weight of rat. This method was used by a similar study. However, several other studies used milligram per kilogram body weight (mg/kg) e.g. 100mg/kg BW and 200mg/kg BW for subchronic toxicity studies. The poly-herbal drink is taken in liquid form by human and this is why i thought that using something like 15ml/kg and 30ml/kg BW will mimic the human consumption of the drink. Human dose is 45ml/70kg. if i have to do the acute toxicity study then i will have to concentrate the herbal drink and that is what am trying to avoid. Can you please recommend a good book or papers that can help design the study properly. Thanks

I would think the critical issue here is the nature of the polyherbal formulation, and the intended method of concentration. If you intend using heat in concentrating the formulation, do you imagine it could in any way affect the stability, or other features of the formulation in question? What toxicity study studies are intending to carry out? And what have you done yet? I would think it is prudent to start with the firmulation as you have it, and run a trial test, and do a gross observation, including behavioural changes. I would assume the end point is not necessarily lethality in your toxicity test.

You can get some good guidance for testing at www.fda.gov. Also see....

http://www.sciencedirect.com/science/article/pii/0272059087901047

http://www.sciencedirect.com/science/article/pii/027869159190023Z

If the polyherbal preparation is sold as liquid, you may administer it to animals as. Such. But in calculating your dose, you still end up with mg/kg if the quantity (mg or g) of the herbs in the preparation are stated. However nothing is wrong with concentrating it at low temp or fixed-drying, it makes calculations easier. In chronic studies, it is allowed to even dissolve the preparation in drinking water throughout the study duration.

I guess you wonder if the differnt volume, not different concentration, could be used for different group in toxicity study design. I think it's OK. As you mentioned, the concentration of test article will be confirmed for human use and not be changed. It's not required to concentrate it for high dose group design. In my opinion, we just need investigate the toxicity on different exposure, don't care calculate with volume or concentration. The dosage could also be described as mg/kg body weight.

But if iv. route for administration, the dosing volume should be thought over.

I think I agree with Hongping wan. At this stage you have to use different volumes and not to bother about concentration. The poly herbal water extract will have different active ingredients so the concentration of which active ingredient you will rely on?

I think you should first carry out your study using the preparation the way humans use it; as such you will have to administer it to the animals in ml/kg. What this means is that you will have to check the product label for the weight or amount in g, mg or kg as the case may be of the polyherbal material that was dissolved into the liquid product you have. By so doing, you will be able to determine the amount in each ml of the preparation you are actually giving to the animals. You have to consider that humans do not concentrate it before using and if your concentration method is not appropriate you may actually be administering something different from what humans consume when they take the preparation. So in order to make your findings really relevant to the people who use this formulation, you may want to consider NOT concentrating it just yet. Guided by the human dose 45ml/70kg, which you stated earlier on, choose appropriate doses for your subchronic toxicity test. Some researchers usually use 3 doses namely; 1/5th of the dose considered as the therapeutic dose, the dose considered as the therapeutic dose and x5 of the dose considered as the therapeutic dose.

@Chigozie Amadi. The end point is not necessarily toxicity, I gut want to find out is the poly-herbal formulation have any effect on biochemical and hematological parameters in rats and by extension in human using low/high dose. So my concern is that the dose for human is 45ml/kg what would a low/high dose in rat be like if I want to use the formulation like that?

@Omoniyi Yemitan. The poly-herbal formulations states the quantity of each of the herbs used in grams(g) and that these are contained in 200ml of the final preparation. On calculating the total weight of herbs it comes to 121g, can I infer that this is 121g/200ml? which is the same as 0.605g/ml or 605mg/ml. Meanwhile a 70kg man will take 45ml of this product as a single dose resulting in 27,225mg/45ml or 27,225mg/70kg. this will give 389mg/kg as the dose taken by human. From this (389mg/kg) what dose would you recommend that i use as low dose and high dose for the rats in subchronic toxicity test?

@warda Abdelgadir. what if the composition on the lackage reads w/v (weight in volume). Can't the human dose be extrapolated to rats

@Flora Aigbe. Many Thanks

You are most welcome

Segun, use 1/5th, human dose and 5x this calculated human dose (i.e. 1/5, 1, 5x) for your study if you choose 3 dose levels. But if 5 doses, you may use 1/5, 1/3, 1, 3x, 5x of the calculated human dose.

@Omoniyi, Thanks

Son dos conceptos, el uno es la composición de la formulación, ej si es líquido mg/kg de material y el otro tiene que ver con la dósis que se pretende administrar, eJ ,mg/kg de peso de animal, si son varias de sustancias, hay que analizar por lo efectos y su equivalencia