Toxicology What is toxicology? The study of the effects of poisons. Poisonous substances are produced by plants, animals, or bacteria. Phytotoxins Zootoxins Bacteriotoxins Toxicant - the specific poisonous chemical. Xenobiotic - man-made substance and/or produced by but not normally found in the body.

Introduction Toxicology is arguably the oldest scientific discipline, as the earliest humans had to recognize which plants were safe to eat. Most exposure of humans to chemicals is via naturally occurring compounds consumed from food plants. Humans are exposed to chemicals both inadvertently and deliberately.

Did You Know ? 92% of all poisonings happen at home. The household products implicated in most poisonings are: cleaning solutions, fuels, medicines, and other materials such as glue and cosmetics. Certain animals secrete a xenobiotic poison called venom, usually injected with a bite or a sting, and others animals harbor infectious bacteria. Some household plants are poisonous to humans and animals.

Swiss physician Paracelsus (1493-1541) credited with being “the father of modern toxicology.” “All substances are poisons: there is none which is not a poison. The right dose differentiates a poison from a remedy.”

Dose/Response Relationships “Everything is poisonous, yet nothing is poisonous” Most substances in too great amounts can be dangerous, but in small amounts are harmless. Ex: table salt, vitamins

Dose response curves illustrate the relationship between concentration and toxicity. Trace concentrations may be very useful, then a certain concentration is reached where the substance becomes toxic.

LD-50,ED-50,and TD-50 Individuals differ in their response to an environmental toxin, so a way to measure the overall toxicity is needed. LD-50 represents the concentration that is lethal to 50% of the population exposed to the toxin.

The lower the LD-50, the more toxic the substance. Some LD-50’s: Sodium Chloride- 4000 mg/kg 2,4-D (weed killer) 368 mg/kg DDT 135 mg/kg Caffeine 127 mg/kg Nicotine 24 mg/kg Strychnine sulfate (rat poison) 3 mg/kg Botulinum toxin 0.00001 mg/kg

In toxicology testing, the most common route of exposure is tested, and is the basis for setting rules for exposure to the toxins Ex: inhalation, skin and eye exposure, ingestion.

Acute vs. Chronic Toxicity Tests Can broadly classify toxicity tests based on length of exposure Acute Toxicity test Drop dead testing Time = 2 days (invertebrates) to 4 d. (fish and mice) LD50 LC50 TLm (median tolerance dose) EC50 (effective concentration) Lose equilibrium, sit on bottom  “ecologically” dead Not very ecologically relevant but quick, relatively cheap (but still ~$700-1,200 per test)

Acute vs chronic toxicity testing (con’t) Growth, reproduction More ecologically relevant data but takes longer, more expensive Shows effect at much lower dose Test requires much more “baby-sitting”

Acute Testing - theory Population of organisms has normally distributed resistance to toxicants  acute toxicity test designed to identify mean response Regulations allow 5% of species to be impacted Most tests only use 2-3 species (up to 6)  not really enough to protect 95% of all species!

Acute Toxicity Test Organisms Use of test species based on Lab hardiness Common Known life cycle Cheap Short-lived

Normal distribution of resistance/sensitivity Mean response Frequency 5% allowable impact Resistance

Chronic toxicity testing Sublethal Time = 7d. to 18 months Endpoints are growth Reproduction brood size (Ceriodaphnia dubia can have 2-3 broods in seven days) Reproductive success Teratogenicity studies (birth defects)

The ED-50 represents the amount that is effective in 50% of the population. Ex: concentration of aspirin needed to be effective in 50% of the population

Toxic responses can be things such as reduced enzyme activity, lowered The TD-50 is defined as the dose that is toxic to 50% of the population. Toxic responses can be things such as reduced enzyme activity, lowered reproduction, or onset of specific symptoms (known to be associated with the toxin. )

All toxicity tests try to determine level of toxicant which will or will not cause an effect NOEC – No Observable Effect Concentration Highest conc not signficantly different from control LOEC – Lowest Observable Effect Concentration Lowest test concentration that is significantly different from control MATC – Maximum Allowable Toxicant Concentration Geometric mean of NOEC and LOEC Often called the “chronic value”

MATC MATC = √NOEC + LOEC

Sources of Pollution Point Source vs. Non-Point Sources: -Point source polluters are single sources of pollution, such as pipes, smokestacks, or spills Non-Point sources (also Area Sources) are spread over the land, and do not have a single outflow of pollution. Ex: runoff from polluted land areas, automobile exhaust

Categories of Pollutants Infectious agents: diseases, spread through interactions of environment and man. EX: Salmonella, a food poisoning bacteria spread via water or food. Giardiasis, a protozoan infection spread via water, or person-to-person contact.

2) Toxic Heavy Metals: -metals with high atomic weight -Pose health hazards to humans and ecosystems -mercury,lead,cadmium,arsenic,gold chromium, vanadium, thallium -most of these metals are by-products of a modern industrialized society

Body Burden of Heavy Metals -Body Burden is defined as the amount of heavy metals contained within an organisms tissue. -heavy metals are accumulated over an organisms lifetime, and biomagnify in the food chain. Human averages: 13 mg mercury, 150mg lead 30mg cadmium.

Biomagnification is the accumulation of a substance up the food chain by transfer of residues of the substance in smaller organisms that are food for larger organisms in the chain. Biomagnification can result in higher concentrations of the substance than would be expected if water were the only exposure mechanism.

Let's look at our food chain to see how biomagnification works Let's look at our food chain to see how biomagnification works. Let's say for example that each piece of plant material has one microscopic drop of methylmercury. One insect eats 25 pieces of plant material, that would mean that each insect would have __________ microscopic drops of methylmercury in its body. One small fish needs 10 insects to live, if each insect has 25 microscopic drops of methylmercury in its body, then one fish would have __________ microscopic drops of methylmercury. One big fish eats 5 small fish to live. Each small fish has __________ microscopic drops of methylmercury in its body, therefore, one big fish would collect a total of __________ microscopic drops of methylmercury in its body. What about you and me? Lets say we eat 1 big fish a day for 3 days. If each big fish has __________ drops of methylmercury in its body then we would collect a total of __________ drops of methylmercury in our body over the 3 days.

3) Organic Compounds: -produced naturally, or synthetically by humans. -compounds containing carbon as an element. -many synthetic organic compounds are used in industrial processes, food additives, pesticides, and drugs.

-Some synthetic organics are called “persistent organic pollutants” or POP’s POP’s have several characteristics that make them particularly bad for the environment. They are carbon-based, and often contain chlorine,which is highly reactive (and toxic) in the environment.

2) They are synthetic 3) They are long-lived in the environment 4) They are very toxic to a variety of organisms 5) They are soluble in fat, so they accumulate within the fatty tissue of organisms 6) They occur in forms which allow them to be transported in a large variety of ways (wind, water, sediment)

Some Organic Pollutants -Aldrin (1949) :Insecticide -Dieldrin (1948) :Insecticide -DDT (1942): Insecticide -PCB’s (1929) : Electrical Insulators -Dioxins (1920’s) :by-product of herbicide production

4)Particulate pollution -small particles of dust, released into the atmosphere by many human activities. Ex: construction, exhaust -Particulates are also released Into the atmosphere by natural processes as well. Ex: volcanoes, wind erosion

Particulates can cause many respiratory problems, from asthma to cancer. Particulate pollution has been declining in the U.S., mostly due to pollution limits on coal fired power plants.