Hello,

I did not find your CAS number but if your structure is essentially the same as 10-epi-gamma-Eudesmol (CAS 15051-81-7) the structure does not have any alerts for mutagenicity or carcinogenicity; however, the Cramer class rules address toxicity potential other than mutagenicity/carcinogenicity.  The actual reference that the toxtree model is based on is given below.  The Class that the compound falls into is based on the responses to a series of questions presented as a decision tree.

Cramer GM, Ford RA, Hall RL (1978). Estimation of toxic hazard—a decision tree approach. Food Cosmet Toxicol 16(3):255-276.

Regards

Thanks a lot Lois. You mentioned isomers:

CAS 117066-77-0: 7-epi-γ-Eudesmol or epi-γ-Eudesmol;

CAS 15051-81-7: 10-epi-γ-Eudesmol or epi-Eudesmol;

However, if the Cramer class rules address toxicity potential other than mutagenicity/carcinogenicity, what is the other toxicity potential?

Hi Roberto,

It could include general organ toxicity or other systemic effects.  Thresholds for the three Cramer Classes were established based on toxicology data for a database of chemicals where no-observed-effect levels were identified for threshold dependent effects.  This work helped form the basis of the threshold of toxicological concern (TTC) procedure for the evaluation of flavours. .

Munro IC, Ford RA, Kennepohl E, Sprenger JG (1996). Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food Chem Toxicol 34(9):829-867.

The following references also may be helpful to address your specific compound.

http://www.efsa.europa.eu/en/141202/docs/141202-p09.pdf

Bhatia S, Schultz T, Roberts D, Shen JKL, Marie Api A (2015). Comparison of Cramer classification between Toxtree, the OECD QSAR Toolbox and expert judgment. Regul Toxicol Pharmacol 71(1):52-62. http://www.ncbi.nlm.nih.gov/pubmed/25460032

Regards

Hi Roberto,

Lois brought up some great points. I suggest that you use multiple methods to determine the Cramer class. You mentioned that you used Toxtree. You should try the Toolbox also and then conduct expert judgment (if possible). There are key questions that may result in discrepancies in the in-silico programs.

Kind Regards

Thanks a lot for your answers.

I wonder, what are the best or your favourite in silico tools for testing natural compounds (i.e. plant flavouring compounds)?