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

Friday, 5/2

Turn in “pre-lab” Take out your LD50 worksheet

Operating Engineers National Hazmat Program

1

Vincent J. Giblin, General President

1293 Airport RoadBeaver, WV 25813

Phone: (304) 253-8674Fax: (304) 253-7758

E-mail: [email protected]

Toxicology in 50 Minutes

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.


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What is toxicology?

The study of the negative effects of

chemicals on living things

A chemical is considered toxic

depending on

– How much of it is necessary to cause harm

– How easily it can enter the body


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Routes of exposure

In order for a chemical to cause injury, it must enter the body– Inhalation

– Ingestion

– Absorption through the skin

– Injection


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Chemicals in the body

Distribution - spread throughout the body Metabolism - broken into smaller

chemical compounds Storage - kept in the body for a long time Excretion - passed out through urine,

feces, exhaled air, or sweat


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Toxic effects

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


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Dose and response

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

Dose-response curve - alcohol

No effect

Relaxed

Slurred speech

Sleep

Coma

Labored breathing

Death


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Acute and chronic exposures

Acute - sudden, brief– A bee sting

Chronic - repeated small doses over time– Smoking cigarettes for years


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Acute and chronic effects

Acute - lasting hours

Chronic - lasting a long

time - possibly years


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LD50 and LC50 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


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Exposure Limits

PEL - permissible exposure limit - airborne concentration enforced by OSHA

STEL - short-term exposure limit -15 minutes four times a day, with l hour free of exposure between each 15 minute exposure

IDLH - immediately dangerous to life and health - maximum airborne concentration which would not interfere with ability to escape


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Good work practices

Read the MSDSs Use PPE when required 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

Information of the potential health hazards of chemicals is derived from...

1) Toxicological studies (in vivo, in vitro)

2) Case reports

3) Epidemiological studies

Toxicity testing

Systematic toxicity testing started in 1960’s

testing guidelines: OECD guidelines, EU guidelines for industrial chemicals

GLP guidelines

Acute toxicity testing acute oral, dermal or inhalation toxicity 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

usually these tests are made with rodents, dermal test quite often with rabbits

LD50/LC50 values (dose level which is caused death to 50% of animals)

Acute toxicity testing, con’t 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

Irritation and corrosion

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<2 or >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

Irritation and corrosion con’t 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<2 or >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

Skin sensitization Traditional Guinea Pig models for skin

sensitization– guinea pig maximization test (GPMT)– Buehler test

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

Assignment Calculate the LD50 for 50% of your

clones for the given substances Circle the most toxic and the least toxic

substances on the list. 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.


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Documents

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