1. Friday, 5/2 4 Turn in “pre-lab” 4 Take out your LD50 worksheet Operating Engineers National Hazmat Program 1

2. Vincent J. Giblin, General President 1293 Airport Road Beaver, WV 25813 Phone: (304) 253-8674 Fax: (304) 253-7758 E-mail: hazmat@iuoeiettc.org Toxicology in 50 Minutes

3. This material was produced under grant number 46C5-HT16 from the Occupational Safety and Health Administration, U.S. Department of Labor. It does not necessarily reflect the views or policies of the U.S. Department of Labor, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

4. Operating Engineers National Hazmat Program 4 What is toxicology? 4 The study of the negative effects of chemicals on living things 4 A chemical is considered toxic depending on –How much of it is necessary to cause harm –How easily it can enter the body

5. Operating Engineers National Hazmat Program 5 Routes of exposure 4 In order for a chemical to cause injury, it must enter the body –Inhalation –Ingestion –Absorption through the skin –Injection

6. Operating Engineers National Hazmat Program 6 Chemicals in the body 4 Distribution - spread throughout the body 4 Metabolism - broken into smaller chemical compounds 4 Storage - kept in the body for a long time 4 Excretion - passed out through urine, feces, exhaled air, or sweat

7. Operating Engineers National Hazmat Program 7 Toxic effects 4 Toxic chemicals disrupt the normal functions of the body. Effects can be –Local - at the site of exposure –Systemic - affecting the entire body target organs - organs or systems where symptoms of exposure appear

8. Operating Engineers National Hazmat Program 8 Dose and response 4 The reaction is dependent on the amount of the chemical received, but... –Some doses are so small they produce no response –Once the maximum reaction has occurred, increasing the dose doesn’t change the reaction

9. Dose-response curve - alcohol No effect Relaxed Slurred speech Sleep Coma Labored breathing Death

10. Operating Engineers National Hazmat Program 10 Acute and chronic exposures 4 Acute - sudden, brief –A bee sting 4 Chronic - repeated small doses over time –Smoking cigarettes for years

11. Operating Engineers National Hazmat Program 11 Acute and chronic effects 4 Acute - lasting hours 4 Chronic - lasting a long time - possibly years

12. Operating Engineers National Hazmat Program 12 LD50 and LC50 4 These terms derive from laboratory tests on animals –LD50 is the dose which when swallowed, injected, or applied directly, kills half the test subjects –LC50 is the concentration of a chemical in a test atmosphere that kills half the test subjects within one hour when inhaled

13. Operating Engineers National Hazmat Program 13 Exposure Limits 4 PEL - permissible exposure limit - airborne concentration enforced by OSHA 4 STEL - short-term exposure limit -15 minutes four times a day, with l hour free of exposure between each 15 minute exposure 4 IDLH - immediately dangerous to life and health - maximum airborne concentration which would not interfere with ability to esc ape

14. Operating Engineers National Hazmat Program 14 Good work practices 4 Read the MSDSs 4 Use PPE when required 4 Practice good hygiene –Don’t eat, drink, smoke, or apply cosmetics around hazardous chemicals –Wash your hands –If showering and changing clothes after your shift is recommended, do so

15. 4 Information of the potential health hazards of chemicals is derived from... 1) Toxicological studies (in vivo, in vitro) 2) Case reports 3) Epidemiological studies

16. Toxicity testing 4 Systematic toxicity testing started in 1960’s 4 testing guidelines: OECD guidelines, EU guidelines for industrial chemicals 4 GLP guidelines

17. Acute toxicity testing 4 acute oral, dermal or inhalation toxicity 4 provides information on acute health hazards likely to arise from acute exposure to the substance by the given route, and on the magnitude of acute toxicity of the substance 4 usually these tests are made with rodents, dermal test quite often with rabbits 4 LD50/LC50 values (dose level which is caused death to 50% of animals)

18. Acute toxicity testing, con’t 4 principle of the acute LD50/LC50 tests: –At least 3 groups of animals are exposed to different concentrations of the chemical, observations of effects and deaths are made, LD50/LC50 value is statistically derived value determined from the dose-response curve by using certain accepted extrapolation methods

19. Irritation and corrosion 4 Acute skin irritation/corrosion test (Draize test) –usually albino rabbits are used, the test substance is applied to the skin of the rabbits and held under the semi-occlusive dressing usually for four hours. The degree of irritation is scored at specified intervals. –NOT if the substance is a strong acid or a strong base (pH 11.5), or it has not caused skin irritation at maximal dosage in acute dermal toxicity test. –Note: albino rabbits are usually more sensitive to the skin irritation/corrosion than humans

20. Irritation and corrosion con’t 4 Acute eye irritation/corrosion test (Draize test) –principle: the test substance is applied to the conjuctival sac of albino rabbit, the effects are observed and scored according to the severity of the effects. Repeated examinations at specified intervals –NOT if the substance is a strong acid or a strong base (pH 11.5), or it is corrosive to the skin –Note: albino rabbits are usually more sensitive to the eye irritation/corrosion than humans –In vitro –methods for eye irritation testing has been developed, but have not yet been good enough to replace in vivo eye irritation test

21. Skin sensitization 4 Traditional Guinea Pig models for skin sensitization –guinea pig maximization test (GPMT) –Buehler test 4 New alternative: Local lymph node assay (LLNA) –measures cellular proliferation in the lymph nodes draining the site of topical application of the substance –more specific, objective and reproducible, gives more quantitative information

22. Assignment 4 Calculate the LD50 for 50% of your clones for the given substances 4 Circle the most toxic and the least toxic substances on the list. 4 Homework: #2: Look over some ingredients in food that you like to eat and look up its LD50. Try to locate an MSDS sheet for the substance and print it out. Operating Engineers National Hazmat Program 22