Toxicology Presented to ES317 y at UWO in

Toxicology • Presented to ES-317 y 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 • LC 50(h, 30) = [3. 3/10][LC 50(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 • LC 50(h, 30) = [5. 1/20][LC 50(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.

H 2 S Data

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 LC 50. • The mean + 2 SD is assigned LC 99. • The mean - 2 SD is assigned LC 01.

Probits • The data between LC 99 and LC 01 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.

Probit Chart For H 2 S

Two Databases for Toxic Chemicals • The UK database as in CPQRA of the CCPS / AICh. E. • 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, ERPG 1, ERPG 2 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 V 1. 1 program in Chemical Plant Hazards Toxicology Probit Data V 1. 1 files. • The user selects a chemical from the d. B, a probit method, a concentration and an exposure time. • The program determines the consequence as shown on the following example.

Probit Data V 1. 1

Probit Data V 1. 1 Chart

H 2 S Animal Data • As an example of the above procedure, the Concord Scientific Data for H 2 S is presented in Chemical Plant Hazard Toxics Toxicology H 2 S 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? • ***