Toxicology

Issues with Toxicology
Extrapolation from acute exposure (scientific experiments) leads to “making educated guesses” about the effects of chronic exposure. Tradeoffs have to be made– which species are we going to protect, and what percentage of that species bears protecting? Rats and mice are sucky analogs for people, so there are a lot of inherent flaws with experimentation. Also, little is known about interactions between toxins.
EPA’s stance on appropriate level of protection
In 1980, the EPA said that aquatic communities can tolerate some stress and occasional adverse effects on a few species. Therefore it is not necessary to protect all of the species all of the time.
Acute Toxicity
Toxic effects resulting from short term (48-96 hours) of exposure to toxin.
Chronic Toxicity
Toxic effects resulting from long term (10% of organism’s life span) exposure to toxin.
Sublethal Toxicity

1. Reproduction

2. Development or growth

3. Behavior

 

Mean Tolerance Limit
Concentration of toxicant at which 50% of organisms have died, also called TL50 or LC50- lethal concentration corresponding to 50% mortality. A measure of acute toxicity.
EC50
Specified effect (not just mortality) on 50% of the organisms after a certain period. A measure of acute toxicity.
Median Survival Times
Time at which 1/2 of the organisms are able to survive given the level of stress. A measure of chronic toxicity.
Incipient Lethal Level
Infinite survival time, calculated by extrapolating median survival time as a function of stress level. A measure of chronic toxicity.
Sublethal chronic toxicity determination
Compare reproduction, behavior, development and growth in exposed group vs. control group.
Chronic Value
Smallest concentration with statistically significant impact vs. control on reproduction
Mean chronic value
Geometric mean of chronic values (root of the product)
EPA Guidelines for Final Acute Value (Aquatic Ecosystem)
Acute tests on 8 different families, determine mean acute value for each species (geo. mean of reported values– could be TLm or EC50). Group species by genera, calculate mean acute value for each genus. Rank then and calculate cumulative probability by dividing rank by rank+1. The 4 genera with cumulative probabilities closest to 0.05 are used to calculate slope and determine final acute value.
EPA Guidelines for Final Chronic Value (Aquatic Ecosystems)
Final Acute Value / Acute:Chronic Ratio
Calculations of Acute:Chronic Ratio

1. Geometric mean if no major trends in acute:chronic

2. if variable, acute:chronic of species with acute value closest to final value

3. Embryos of larva and barnacles, bivalve mollusks, sea urchins, lobsters, crabs, shrimp, abalone -> acute:chronic= 2

4. If acute:chronic < 2, assume 2

Final Plant Toxicity Value
The minimun concentration of the toxicant that statistically significantly reduces plant growth
Criterion maximum concentration
1-hour average concentration not to be exceeded more than once every 3 years. Is equal to half the final acute value because the final acute value is based on lethal effect, and you want to protect organisms from sublethal stresses.
Criterion Continuous Concentration
4-day average concentration not to be exceeded more than once every three years and is equal to the smaller of the final chronic and final plant values.
Complication Factors

1. Toxicity is dependent on environmental conditions (temperature, water hardness)

2. Conditioning and acclimation

3. Interactions between toxicants

No Interaction Between Toxicants
After TLm, 1.2 organisms are dead
Antagonistic Interaction Between Toxicants
After TLm fewer than 1/2 are dead
Strictly Additive Interaction Between Toxicants
Percent dead is exactly what one would expect from doubling the concentration of either toxicant
Supra-additive/ Syngergistic
The percent of organisms dead is more than one would expect if the concentration of either toxicant was doubled
Infra-additive Interaction Between Toxicants
The percent of organisms dead is greater than 50 but less than one would expect from doubling the concentration of either toxicant
NOAEL
Lower bound to threshold dose that causes some adverse effect, this term is associated with public health/noncarcinogenic effects
LOAEL
Upper bound to threshold dose that causes some adverse effect, term is associated with public health/noncarcinogenic effects
Reference Dose
Maximum acceptable rate of consumption of toxic substance per unit body weight (related to levels above by dividing by the uncertainty factor)
Human Health Criterion
Numeric values limiting the amounts of chemicals present in waters: (Reference dose * body weight)/(water consumption rate + fish/shellfish consumption rate * practical bioconcentration factor)
Acceptable Daily Intake
Refence Dose * body weight
Maximum Tolerated Dose
Refers to the highest dose of a radiological or pharmacological treatment that will produce the desired effect without unacceptable toxicity; this term is used in association with public health/carcinogenic effects
Problems with Rodent Experimentation

1. Inbreeding = prone to cancers

2. Response of different rat populations variable

3. Overfeeding

4. Assumption that MTD extrapolates to low doses (no threshold)

5. Hormesis?