Presentation on theme: "Toxicology Presented to ES-317y at UWO in 1999 Dick Hawrelak."— Presentation transcript:
Toxicology Presented to ES-317y at UWO in 1999 Dick Hawrelak
Consequences to Humans Consequences of toxic chemical exposure are usually derived from animal experiments (rats, mice, dogs, etc.). Search the internet for “Holocaust” for the exception to this statement.
Uncertainties in Animal Data The uncertainties in translating small animal data to data relevant for humans are large and therefore safety factors are included in the modeling.
Acute Versus Chronic Injury Emergency planners generally deal with acute or short term lethal injury (2000 people died in a few days in Bhopal toxic release). Environmentalists deal with longer term chronic injury (eg cancer after 20 years of exposure).
Two Acute Categories Local Irritantia (LI) deals with direct damage to the lungs. Sytematically Acting Agents (SAA) deals with damage to the body via the blood and distribution in the body.
Local Irritantia LC50(h,30) = [3.3/10][LC50(r,30) (for rats). Animals have a higher adsorption rate, safety factor set at 5 Humans have a higher respiratory rate in accident situations, safety factor set at 2 Hence, a safety factor of 10 is used in LI.
Systematically Acting Agents LC50(h,30) = [5.1/20][LC50(r,30) A large uncertainty factor of 10 is introduced for blood effects. Humans have a higher respiratory rate in accident situations, safety factor set at 2. Hence a safety factor of 20 is used in SAA.
Convert Animal Data to Humans Once experimental data is available, a standard regression line is drawn through all the converted data (Animals to Humans). The data is plotted as LN(time) as the x-axis and LN(Conc) as the y-axis.
Standard Deviations About the Regression Line. One standard deviation covers 67% of the data points. Two standard deviations covers 95% of the data points. The regression line is assigned LC50. The mean + 2SD is assigned LC99. The mean - 2SD is assigned LC01.
Probits The data between LC99 and LC01 can be converted to regular standard intervals by the use of a probit equation. Pr = a + b Ln[(C^n)(t)] n = 1 / m where m is the slope of the regression curve. Ln is the Natural Log. a and b are constants to suit the intermediate LC values.
Two Databases for Toxic Chemicals The UK database as in CPQRA of the CCPS / AIChE. The Dutch database as in Prince Maritus lab (Green Book by TNO). The two databases give different answers for acute injury rates. The differences remain unresolved and are being debated in academia.
The Holocaust Data for HCN CPQRA gives a fatal dose at 5 minutes for 2,000 ppmv exposure. TNO gives a fatal dose at 0.5 minutes for 2,000 ppmv exposure.
Other Conflicting Data Industrial hygienists have used STEL, TLV, ERPG1, ERPG2 and IDLH for years. These concentration / time values should mesh smoothly with the acute time / concentration data. Often adjustment have to be made to have a set of data that is satisfactory to both industrial hygienists and emergency planners.
Probit Program Toxic consequences can be determined using the Probit Data V1.1 program in Chemical Plant Hazards \ Toxics \ Toxicology \ Probit Data V1.1 files. The user selects a chemical from the dB, a probit method, a concentration and an exposure time. The program determines the consequence as shown on the following example.
H2S Animal Data As an example of the above procedure, the Concord Scientific Data for H2S is presented in Chemical Plant Hazard \ Toxics \ Toxicology \ H2S Data file. This technology is quite complex and is generally offered at the graduate level. Work is in progress to make this more understandable at the undergraduate level.
Possible Exam Question Describe acute versus chronic injury. What two databases are available that describe the toxicity of certain chemicals? ***