QSAR Effects
Estimating Chemical ActivityWhy Not Use an Equation for Everything?ECOSARCATABOLRelevant Publications
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Estimating Chemical Activity
Environmental and human health scientists have studied the toxicity and biodegradation 
of molecules and have observed that these activities can be predicted from structure. For example, the more carbon atoms on a molecule, the more toxic it becomes. The more oxygen and nitrogen atoms on a molecule, the less toxic it is.Toxicity tests with many chemicals have generated enough data to make equations that can be used to calculate toxicity and biodegradation based on chemical structure. We refer to toxicity and biodegradation as activities. We are not just predicting a chemical property, like the boiling point, but we are actually predicting what the molecule will do in the environment.
The equations used are referred to as Quantitative Structure Activity Relationships (QSARs). This is a complicated area of science, and the toxicity of all compounds cannot be predicted from equations. But when we can use an equation, we do.
back to topWhy Not Use an Equation for Everything
There are two basic problems with using equations.
There are two basic problems with using equations.
We cannot predict the toxicity and biodegradation of all compounds from equations.
Chemicals can be divided into different families based on their structure. To develop a good QSAR, 15 to 50 (or more) effect values on chemicals from the same family are needed. That is a lot of data to generate one equation for one chemical family. With thousands of chemical families, we just do not have enough data to predict the toxicity and biodegradation of them all. Additional research is ongoing and more QSARs are being developed, but it will still be a long time before a QSAR is available for all compounds.
Chemicals can be divided into different families based on their structure. To develop a good QSAR, 15 to 50 (or more) effect values on chemicals from the same family are needed. That is a lot of data to generate one equation for one chemical family. With thousands of chemical families, we just do not have enough data to predict the toxicity and biodegradation of them all. Additional research is ongoing and more QSARs are being developed, but it will still be a long time before a QSAR is available for all compounds.
Predictions are never as good as real data.
Tomorrow's weather, the results of the next election, and who is going to win the big game are all examples of predictions. When the weather, the results of the election, or the outcome of the big game is important, we don't want to rely on predictions, we want to know the facts. We consider the prediction to be uncertain, even if predictions have been fairly accurate in the past.
It is the same with QSARs: The results may be pretty close to reality but we never really know until we run the test. As a result, scientists only use QSARs when they need an approximate value. For example, if a chemical is going to exist in the environment at 0.001 g/L and QSARs predict the safe concentration in the environment is 1000 g/L, the toxicologist might decide that it is not worth the time, resources and effort to conduct a toxicity test. Even if the QSAR is close, the environment will not suffer and testing resources can be spent on compounds that pose a greater threat to the environment. For more on risk assessment and how decisions are made, see the environmental risk assessment page.
Tomorrow's weather, the results of the next election, and who is going to win the big game are all examples of predictions. When the weather, the results of the election, or the outcome of the big game is important, we don't want to rely on predictions, we want to know the facts. We consider the prediction to be uncertain, even if predictions have been fairly accurate in the past.
It is the same with QSARs: The results may be pretty close to reality but we never really know until we run the test. As a result, scientists only use QSARs when they need an approximate value. For example, if a chemical is going to exist in the environment at 0.001 g/L and QSARs predict the safe concentration in the environment is 1000 g/L, the toxicologist might decide that it is not worth the time, resources and effort to conduct a toxicity test. Even if the QSAR is close, the environment will not suffer and testing resources can be spent on compounds that pose a greater threat to the environment. For more on risk assessment and how decisions are made, see the environmental risk assessment page.
In summary, when a good QSAR relationship exists for a family of compounds and when an estimate of the toxicity value or biodegradation rate is good enough for the risk assessment, QSAR approaches are used.
P&G has developed a series of its own QSARs and continues to develop new relationships. One of our most recent QSARs is a biodegradation prediction tool called CATABOL. When we need data for a compound that we do not have a QSAR equation for, we review the literature to find a good equation or we use the U.S. EPA's ECOSAR program.
To better understand how humans respond to our ingredients, P&G uses an expert system called DEREK
to assess skin sensitisation, irritation, carcinogenicity or reproductive affects. To predict mutagenicity , P&G developed TIMES . TIMES makes predictions on the parent molecule and then looks for the potential for metabolic activation or deactivation back to top ECOSAR
ECOSAR (Ecological Structure Activity Relationships) is a computer program used to estimate the toxicity of chemicals to aquatic organisms. To use this program, some chemistry background is useful since for many compounds you will need to enter the compound's structure using SMILES notation. Fortunately, the HELP section of the program contains all the information needed to learn about SMILES. Although the program predicts both acute and chronic toxicity for many compounds, we prefer to use the acute toxicity relationships because they are usually based on more compounds and more data and thus we have greater confidence in the results. In using any QSAR prediction, it is important to understand how many compounds the QSAR is based on and whether they are similar to the compound you are interested in. back to topCATABOL
Biodegradation is an important environmental process because it results in the destruction of the ingredient. If the ingredient no longer exists, we don't have to worry about it anymore. However, some compounds do not biodegrade all the way to CO2. Metabolism (the breakdown of the molecule by bacteria) stops before the compound is fully degraded, leaving a partially degraded compound called a metabolite. Due to the importance of biodegradation for P&G products and the need to understand the formation of metabolites , we developed a QSAR program called CATABOL. CATABOL predicts the biodegradation pathway and predicts the possibility that degradation may stop at one or more metabolites. back to topSome Relevant Publications Authored by P&G Scientists
- Cronin, M., Jaworska, J., Walker, J., Comber, M., and Watts. C. Use Of QSARs in International Decision-Making Frameworks to Predict Ecological Effects and Environmental Fate of Chemical Substances. Environmental Health Perspectives, in Press.
- Dyer, S.D., Lauth, J.R., Morrall, S.W., Herzog, R.R., and Cherry, D.S., 1997. Development of a Chronic Toxicity Structure-Activity Relationship for Alkyl Sulfates. Environmental Toxicology and Water Quality, 12, pp. 295-303.
- Dyer, S.D., Stanton, D.T., Lauth, J.R., and Cherry, D.S., 2000. Acute and Chronic Structure Activity Relationships for Alcohol Ethersulfates. Environmental Toxicology and Chemistry, 19, pp. 608-616.
- Jaworska, J., Dimitrov, S., Nikolova, N., and Mekenyan, O., 2002. Chemical Biodegradability. Probabilistic Prediction Based on a Metabolic Pathway. SAR and QSAR in Environmental. Research, 13, pp. 307-323.
- Jaworska, J., Dimitrov, S., Nikolova, N., and Mekenyan, O., 2002. Chemical Biodegradability. Probabilistic Prediction Based on a Metabolic Pathway. SAR and QSAR in Environmental. Research, 13, pp. 307-323.
- Jaworska, J., Howard, P., and Boethling, R.S., 2003. Quantitative Structure Biodegradadation Relationships - A Review. Environmental Toxicology and Chemistry, in Press.
- Morrall, D.D., Belanger, S.E., and Dunphy, J.C. Acute and Chronic Aquatic Toxicity Structure-Activity Relationships for Alcohol Ethoxylates. Ecotoxicology and Environmental Safety, in Press.
- Morrall, S.M., Rosen, M.J., Zhu, Y., Versteeg, D.J., and Dyer, S.D., 1997. Physicochemical Descriptors for Development of Aquatic Toxicity QSARs for Surfactants. In Chen, F. and Schuurmann, G. (Eds.), QSAR '96, 7th International Workshop on QSARs in Environmental Sciences. SETAC Press, Pensacola, FL, pp. 299-313.
- Rosen, M.J., Li, F., Morrall, S.M., and Versteeg, D.J., 2001. The Relationship between the Interfacial Properties of Surfactants and Their Toxicity to Aquatic Organisms. Environmental Science and Technology, 35, pp. 954-959.
- Versteeg, D.J., Stanton, D.T., Pence, M.A., and Cowan, C.E., 1997. Effects of Surfactants on the Rotifer, Brachionus Calyciflorus, in a Chronic Toxicity Test and the Development of QSARs. Environmental Toxicology and Chemistry, 16, pp. 1051-1058.
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