Acute Dermal Toxicity Procedure

The acute dermal LD50 provides an estimate of the toxicity of a substance by the dermal route of exposure. As for any toxicity study dealing with animals all weight- of-the- evidence analysis dealing with the potential dermal toxicity of the test chemical should have been already evaluated before proceeding to the in vivo test.

Sample or test chemical  should not be applied at a doses that are known to cause marked distress or pain. Usually, rat are the subject animal of these procedure. Females are more preferred but see to it that the animals are non pregnant.

The rats dorsal part are shaved around 10 percent of its total body surface area a day prior to testing. On the day of the procedure the sample or test chemical is applied on the shaved dorsal part of the rats thinly and uniformy. The sample should be hold in place  / with contact on skin for 24 hours by putting porous gauze dressing and non irritating tape on the sample.

If there are limited information about the sample a range finding study should be done first to determine the starting dose for the main study. On range finding study you will subject one animal to a dose of 200 mg/kg for 24 hours and after 24 hours all remaining sample should be wipe-off of the dorsal part of the animal. If the animal survived until 48 hours you can continue to the next dose which is 1000 mg/kg. A new animal will be dose with 1000 mg/kg if the animal die your main study starting dose is 200 mg/kg . if the animal survived a new set of animal will be tested for a dose of 2000 mg/kg , if after 48 hours the animal survived the main study starting dose would be 2000 mg/kg but if it died your starting dose is 1000 mg/kg.

Main Study

There are 4 doses that can be a starting point for dosing : 50 mg/kg, 200 mg/ kg, 1000 mg/kg, and 2000 mg/kg.  Lets’ assume that base on your range finding study the starting dose is 200 mg/kg. So, you need  to apply 200 mg/kg of the sample to two animals (200mg/kg per animal).If the animal survived after 48 hours then proceed to the next higher dose which is 1000 mg/kg. Dose 2 new animals (1000 mg/kg) after 48 hours if one animal die  the sample is classified as GHS (Globally Harmonized System) category 4 , if both animal die then the sample is classified as GHS (Globally Harmonized System) category 3. If both animal survive then proceed to the next higher dose which is 2000 mg/kg. Dose 2 new animals (2000 mg/kg) after 48 hours if one animal die  the sample is classified as GHS (Globally Harmonized System) category 5 , if both animal die then the sample is classified as GHS (Globally Harmonized System) category 4.  If both animal survive then the sample is classified as GHS (Globally Harmonized System) category 5/unclassified.

For a more detailed explanation read OECD 402.

If you are reading until these part I would like to congratulate you for having the patience to read this. As a sign of gratitude I will tell you a simple rule about this procedure that will save you a lot of time. If you are testing a mixture products like pesticide, biocide and other chemicals  and if the  Acute Oral toxicity of this product is above 2000 mg /kg bw you don’t need to test these product for Acute Dermal Toxicity, you can waive it  because most of the time the resulting Acute Dermal Toxicity is also 2000 mg / kg bw.