Toxicology: Nlom: Exposure Standards/guidelines

Front 1

What are exposure standards and guidelines?

Back 1

Exposure standards and guidelines are developed by governments to protect the public from harmful substances and activities that can cause serious health problems. Exposure standards and guidelines are the products of risk management decisions.

Front 2

Risk assessments provide regulatory agencies with what?

Back 2

Risk assessments provide regulatory agencies with estimates of numbers of persons potentially harmed under specific exposure conditions. Regulatory agencies then propose exposure standards and guidelines which will protect the public from unacceptable risk.

Front 3

Exposure standards and guidelines usually provide what for various media that cannot be exceeded. Alternatively, these standards may also be what?

Back 3

Exposure standards and guidelines usually provide numerical exposure levels for various media (such as food, consumer products, water and air) that cannot be exceeded. Alternatively, these standards may be preventive measures to reduce exposure (such as labeling, special ventilation, protective clothing and equipment, and medical monitoring).

Front 4

What are the two types of exposure standards and guidelines?

Back 4

1. Standards

2. Guidelines

Front 5

Describe 'standards'?

Back 5

These are legal acceptable exposure levels or controls issued as the result of congressional or executive mandate. They result from formal rule making and are legally enforceable. Violators are subject to punishment, including fines and imprisonment.

Front 6

Describe 'guidelines'?

Back 6

These are recommended maximum exposure levels which are voluntary and not legally enforceable. Guidelines may be developed by regulatory and non-regulatory agencies, or by some professional societies.

Front 7

Federal and state regulatory agencies have the authority to issue what?

Back 7

Federal and state regulatory agencies have the authority to issue permissible exposure standards and guidelines.

Front 8

Federal and state regulatory agencies have the authority to issue permissible exposure standards and guidelines. List 3 categories they include.

Back 8

1. Consumer Product Exposure Standards and Guidelines

2. Environmental Exposure Standards and Guidelines

3. Occupational Exposure Standards and Guidelines

Front 9

Exposure standards or guidelines are:





Unacceptable levels of exposure that must be avoided




Acceptable levels of exposure that should not be exceeded

Back 9

Exposure standards or guidelines are acceptable levels of exposure that should not be exceeded. These levels should protect the public from harmful exposures.

Front 10

Legal exposure standards are:





Acceptable exposure levels that are enforceable if exceeded.




Acceptable exposure levels which are not legally enforceable and adherence is voluntary.




Developed by the Department of Health and Human Services (DHHS) and professional societies.

Back 10

Legal exposure standards are acceptable exposure levels that are enforceable if exceeded. Violators are subject to punishment, including fines and imprisonment.

Front 11

Manufacturers of new pharmaceuticals are required to obtain what before their products can be marketed?

Back 11

Manufacturers of new pharmaceuticals are required to obtain formal FDA approval before their products can be marketed.

Front 12

Drugs intended for use in humans must be tested in ? to determine toxic dose levels as a part of the ?.

Back 12

Drugs intended for use in humans must be tested in humans (in addition to animals) to determine toxic dose levels as a part of the new drug application (NDA).

Front 13

What does the NDA cover?

Back 13

The NDA covers all aspects of a drug's effectiveness and safety, including:

1. Pharmacokinetics and pharmacological effects

2. Metabolism and mechanism of action

3. Associated risks of the drug

4. Intended uses and their effectiveness

5. Benefit-risk relationship

6. Basis for package inserts supplied to physicians

Front 14

The FDA does not what for drugs? Instead, what does the FDA approve?

Back 14

The FDA does not issue exposure standards for drugs. Instead, FDA approves an NDA which contains guidance for usage and warnings concerning effects of excessive exposure to the drug.

Front 15

The manufacturer is required to provide NDA information to whom?

Back 15

The manufacturer is required to provide this information to physicians prescribing the drug as well as to the others that may purchase or use the drug.

Front 16

Information on a drug's harmful side effects is provided in three main ways: List them.

Back 16

1. Labeling and package inserts that accompany a drug and explain approved uses, recommended dosages, and effects of overexposure

2. Publication of information in the Physicians' Desk Reference (PDR)

3. Information dissemination to physicians via direct mailing or by publications in medical journals

Front 17

The package insert labels and the PDR contain what 11 pieces of information pertaining to the drugs?

Back 17

1. Description

2. Clinical pharmacology

3. Indications and usage

4. Contraindications

5. Warnings

6. Precautions

7. Adverse reactions

8. Interactions

9. Overdosage

10. Available forms

11. Dosage and administration

Front 18

The FDA is responsible for the approval of what?

Back 18

The FDA is responsible for the approval of food additives.

Front 19

FDA standards are different depending on what?

Back 19

Standards are different depending on whether they are direct food additives or indirect food additives.

Front 20

Direct food additives are what? Give examples. Approval usually designates the maximum allowable concentrations (e.g., 0.05%) in a food product.

Back 20

Direct food additives are intentionally added to foods for functional purposes. Examples of direct food additives are processing aids, texturing agents, preservatives, flavoring and appearance agents, and nutritional supplements. Approval usually designates the maximum allowable concentrations (e.g., 0.05%) in a food product.

Front 21

What are indirect food additives?

Back 21

Indirect food additives are not intentionally added to foods and they are not natural constituents of foods. They become a constituent of the food product from environmental contamination during production, processing, packaging and storage. Examples of indirect food additives are antibiotics administered to cattle, pesticide residues remaining after production or processing of foods, and chemicals that migrate from packaging materials into foods. Exposure standards indicate the maximum allowable concentration of these substances in food.

Front 22

New direct food additives must undergo what?

Back 22

New direct food additives must undergo stringent review by FDA scientists before they can be approved for use in foods.

Front 23

The manufacturer of a direct food additive must provide what?

Back 23

The manufacturer of a direct food additive must provide evidence of the safety of the food additive in accordance with specified uses.

Front 24

The safety evaluation of a direct food additive is conducted by what?

Back 24

The safety evaluation is conducted by the toxicity testing and risk assessment procedures previously discussed with derivation of the ADI.

Front 25

In contrast to pharmaceutical testing, virtually all toxicity evaluations are conducted with what?

Back 25

In contrast to pharmaceutical testing, virtually all toxicity evaluations are conducted with experimental laboratory animals.

Front 26

In 1958, with an amendment to what, the FDA was required to approve all new food additives?

Back 26

In 1958, with an amendment to the Food, Drug and Cosmetic Act (FDCA), FDA was required to approve all new food additives.

Front 27

In 1958; the law at that time decided that all existing food additives were generally what?

Back 27

The law at that time decided that all existing food additives were generally recognized as safe (known as GRAS) and no exposure standard was developed. Many of these GRAS substances have more recently been re-evaluated and maximum acceptable levels have been established.

Front 28

The FDA re-evaluation of GRAS substances requires what?

Back 28

The FDA re-evaluation of GRAS substances requires that specific toxicity tests be conducted based on the level of the GRAS substance in a food product. For example, the lowest level of concern is for an additive used at 0.05 ppm in the food product. Only short-term tests (a few weeks) are required for those compounds. In contrast, a food additive used at levels higher than 1.0 ppm must be tested for carcinogenicity, chronic toxicity, reproductive toxicity, developmental toxicity, and mutagenicity.

Front 29

The 1958 amendment to the FDCA law for FDA is known as what?

Back 29

The 1958 amendment to the FDCA law for FDA is known as the Delaney Clause.

Front 30

What does the Delaney Clause prohibit?

Back 30

This clause prohibits the addition of any substance to food that has been shown to induce cancer in man or animals. The implication is that any positive result in an animal test, regardless of dose level or mechanism, is sufficient to prohibit use of the substance. In this case, the allowable exposure level is zero.

Front 31

Consumer exposure standards are developed for hazardous substances and articles by who?

Back 31

Consumer exposure standards are developed for hazardous substances and articles by the Consumer Product and Safety Commission (CPSC).

Front 32

Consumer Product and Safety Commission's authority under the Federal Hazardous Substance Act pertains to what?

Back 32

Consumer Product and Safety Commission (CPSC). Their authority under the Federal Hazardous Substance Act pertains to substances other than pesticides, drugs, foods, cosmetics, fuels, and radioactive materials.

Front 33

The CPSC requires a warning label on a what? Highly toxic substances are labeled with what? Less toxic substances are labeled with what?

Back 33

The CPSC requires a warning label on a consumer product which is toxic, corrosive, irritant, or sensitizer. Highly toxic substances are labeled with DANGER; less toxic substances are labeled with WARNING or CAUTION.

Front 34

The basis for highly toxic is death in laboratory ? at an oral dose of ?, an inhaled dose in ? of ? , and a ? in ? of ?.

Back 34

The basis for highly toxic is death in laboratory rats at an oral dose of 50 mgs, an inhaled dose in rats of 200 ppm for one hour, and a 24-hour dermal dose in rabbits of 200 mg/kg.

Front 35

A substance is corrosive if it causes what?

Back 35

A substance is corrosive if it causes visible destruction or irreversible damage to the skin or eye.

Front 36

When is a substance considered an irritant?

Back 36

If it causes damage which is reversible within 24 hours, it is designated an irritant.

Front 37

What is sufficient for the designation of a substance as a sensitizer?

Back 37

An immune response from a standard sensitization test in animals is sufficient for designation as a sensitizer.

Front 38

Exposure standards for pharmaceuticals are:





Issued by the Food and Drug Administration as legal standards




Developed by the Environmental Protection Agency




Recommended guidance developed by the FDA

Back 38

Exposure standards for pharmaceuticals are recommended guidance developed by the FDA. Exposure guidance is a part of the package insert labels and is published in the Physicians' Desk Reference. Physicians are not obligated to conform to the recommended guidance and can exceed usage guidelines and use their medical judgment.

Front 39

The FDA develops exposure standards for both direct food additives and indirect food additives. An example of an indirect food additive is:





A substance added to foods as a preservative




A pesticide residue encountered during production or processing of foods




A nutritional supplement, e.g., Vitamin A

Back 39

The FDA develops exposure standards for both direct food additives and indirect food additives. An example of an indirect food additive is a pesticide residue encountered during production or processing of foods.

Front 40

Under the Delaney clause, the FDA is:





Prohibited from allowing the addition of any substance to foods that has been shown to cause cancer in humans or animals




Authorized to establish exposure standards for substances that have been shown to cause cancer in humans or animals




Authorized to determine acceptable exposure levels for indirect food additives that are known to cause cancer in humans and animals

Back 40

Under the Delaney clause, the FDA is prohibited from allowing the addition of any substance to foods that has been shown to cause cancer in humans or animals. The Delaney Clause is a highly controversial law. Other regulatory statutes allow risk assessments to determine allowable exposure levels for carcinogenic substances.

Front 41

Who is responsible for several laws that require determination and enforcement of exposure standards?

Back 41

The Environmental Protection Agency is responsible for several laws that require determination and enforcement of exposure standards. In addition, they have the authority to prepare recommended exposure guidelines for selected environmental pollutants.

Front 42

The EPA is responsible for developing exposure standards for what?

Back 42

1. Pesticides

2. Water pollutants

3. Air pollutants

4. Hazardous wastes

Front 43

Pesticides can not be marketed until they have been what?

Back 43

Pesticides can not be marketed until they have been registered by the EPA in accordance with the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

Front 44

In order to obtain registration, a pesticide must undergo what?

Back 44

In order to obtain registration, a pesticide must undergo an extensive battery of toxicity tests, chemistry analyses, and environmental fate tests.

Front 45

In cases where the toxicity warrants, a pesticide may be approved for what?

Back 45

In cases where the toxicity warrants, a pesticide may be approved for restricted uses.

Front 46

A primary exposure standard for pesticides is what? This standard specifies what?

Back 46

A primary exposure standard for pesticides is the pesticide tolerance for food use. This standard specifies the amount of pesticide that is permitted on raw food products (e.g., tolerance for chlorpyrifos on corn).

Front 47

Water pollutants are regulated by what two laws

Back 47

1. The Safe Drinking Water Act (SDWA)

2. The Clean Water Act (CWA).

Front 48

Under the SDWA, the EPA conducts what?

Back 48

Under the SDWA, the EPA conducts risk assessments and issues maximum contaminant levels (MCLs) for chemicals in drinking water.

Front 49

What is a maximum contaminant level (MCLs)?

Back 49

The MCL is the acceptable exposure level which, if exceeded, requires immediate water treatment to reduce the contaminant level. For example, the MCL for trichloroethylene is 0.005 mg per liter of water.
.

Front 50

In addition to establishing MCLs, the EPA can propose recommended what?

Back 50

In addition to establishing MCLs, the EPA can propose recommended exposure guidance for drinking water contamination

Front 51

As an interim procedure, what may be recommended for long term exposures to contaminants in drinking water

Back 51

As an interim procedure, maximum contaminant level goals (MCLGs) may be recommended for long term exposures to contaminants in drinking water.

Front 52

Generally, no allowable exposure can be recommended for a what?

Back 52

Generally, no allowable exposure can be recommended for a carcinogenic chemical.

Front 53

What is an HA?

Back 53

EPA prepares health advisories (HAs) as voluntary exposure guidelines for drinking water contamination.

Front 54

The HAs provide exposure limits for what exposure periods?

Back 54

The HAs provide exposure limits for 1-day, 10-day, longer-term, or lifetime exposure periods.

Front 55

HAs pertain only to what risks?

Back 55

They pertain only to non-carcinogenic risks.

Front 56

How does the formula for HAs differ from that for the ADI or RfD?

Back 56

The formula used to derive a health advisory differs from that for the ADI or RfD in that the HAs pertain to short-term as well as long-term exposures. In addition, human body weight and drinking water consumption are included in the formula.

Front 57

The basic formula for an HA is in what units?

Back 57

The basic formula for an HA is in mg/L.

Front 58

Give the basic formula for HA.

Back 58

HA = ((NOAEL or LOAEL) * Body wt.)/ (water consumption * UF)

(body wt = 10kg for a child; 70kg for an adult)

(Water consumption = 1 L/day for child; 2 L/day for an adult)

(UF = uncertainty factor)

Front 59

What must conform with the human exposures covered by the HAs? Give an example.

Back 59

The durations and exposure route (oral) of the toxicology studies to be employed for HA assessments must conform with the human exposures covered by the HAs. For example, the NOAEL or LOAEL for derivation of a 10-day HA would be obtained from an animal toxicology study of approximately 10 days duration (routinely 7-14 day toxicity studies).

Front 60

A longer-term HA applies to who?

Back 60

A longer-term HA applies to humans drinking contaminated water for up to 7 years (10% of a human's 70-year lifespan). Since 90 days is about 10% of a rats expected lifespan, the 90-day subchronic study with rats is appropriate for derivation of the longer-term HA assessment

Front 61

A life-time HA (representing lifetime exposure to a toxicant in drinking water) is also determined for what?

Back 61

A life-time HA (representing lifetime exposure to a toxicant in drinking water) is also determined for non-carcinogens. The procedure uses the RfD risk assessment with adjustments for body weight of an adult human (70 kg) and drinking water consumption of 2 L/day.

Front 62

In addition to drinking water standards, the EPA is authorized under the Clean Water Act (CWA) to issue what?

Back 62

In addition to drinking water standards, the EPA is authorized under the Clean Water Act (CWA) to issue exposure guidance for control of pollution in ground water. The intent is to provide clean water for fishing and swimming rather than for drinking purposes. It provides a scheme for controlling the introduction of pollutants into navigable surface water. The recommendations for ground water protection are known as ambient water quality criteria.

Front 63

The ambient water quality criteria are intended to control what?

Back 63

The ambient water quality criteria are intended to control pollution sources at the point of release into the environment. While these criteria may be less restrictive than the drinking water standards, they usually are the same numeric value. For example, the MCL (for drinking water) and the ambient water quality criteria (for ground water) for lead are the same (0.05 mg per liter of water).

Front 64

What are issued by EPA under the Clean Air Act (CAA)?

Back 64

Air emission standards are issued by EPA under the Clean Air Act (CAA).

Front 65

The CAA authorizes the issuance of what for air pollution?

Back 65

The CAA authorizes the issuance of national ambient air quality standards (NAAQS) for air pollution.

Front 66

What are the different types of NAAQS?

Back 66

There are two types of NAAQS. Primary NAAQS pertain to human health, whereas secondary NAAQS pertain to public welfare (such as crops, animals, and structures).

Front 67

NAAQS have been established for the what major atmospheric pollutants?

Back 67

NAAQS have been established for the following major atmospheric pollutants: carbon monoxide, sulfur oxide, oxides of nitrogen, ozone, hydrocarbons, particulates, and lead.

Front 68

When air emissions exceed the NAAQS levels, the polluting industry must do what?

Back 68

When air emissions exceed the NAAQS levels, the polluting industry must take control measures to reduce emissions to the acceptable level.

Front 69

Hazardous wastes are regulated under what?

Back 69

Hazardous wastes are regulated under the Resource Conservation and Recovery Act (RCRA) and the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), commonly known as Superfund.

Front 70

RCRA regulates hazardous chemical waste produced by what?

Back 70

RCRA regulates hazardous chemical waste produced by industrial processes, medical waste and underground storage tanks.

Front 71

The main purpose of CERCLA is to clean up what?

Back 71

The main purpose of CERCLA is to clean up hazardous waste disposal sites.

Front 72

EPA has established standards known as Reportable Quantities (RQs). What are these?

Back 72

Related to hazardous waste disposal. EPA has established standards known as Reportable Quantities (RQs). Companies must report to EPA any chemical release that exceeds the RQ. The RQ for most hazardous substances is one pound.

Front 73

ATSDR derives Minimal Risk Levels (MRLs) for what?

Back 73

ATSDR derives Minimal Risk Levels (MRLs) for noncancer toxic effects.

Front 74

MRLs are estimates of what?

Back 74

MRLs are estimates of daily human exposures that are likely to be without an appreciable risk of adverse effects over a specified duration of exposure. MRLs are derived for acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more) exposures for inhalation or oral routes.

Front 75

The exposure standard established by the EPA for pesticides that may contaminate foods is known as the:





Pesticide Direct Food Additive Level




Reportable Quantity




Pesticide Tolerance for Food Use

Back 75

The exposure standard established by the EPA for pesticides that may contaminate foods is known as the Pesticide Tolerance for Food Use. The EPA is responsible for establishing the pesticide tolerances whereas the FDA is responsible for enforcement actions in the event tolerance levels are exceeded.

Front 76

The EPA establishes exposure standards for chemical contaminants in drinking water which are known as:





Maximum Contaminant Levels




Ambient Water Quality Criteria




Maximum Contaminant Level Goals

Back 76

The EPA establishes exposure standards for chemical contaminants in drinking water which are known as Maximum Contaminant Levels. The MCL is the acceptable exposure level of a chemical in drinking water which, if exceeded, requires immediate treatment of the water to reduce the contaminant level.

Front 77

The ATSDR derives estimated levels for daily human exposure to chemicals that are likely to be without an appreciable risk of adverse effects for specified periods of exposure. These are know as:





Health Advisories




National Ambient Air Quality Standards




Minimum Risk Levels

Back 77

The ATSDR derives estimated levels for daily human exposure to chemicals that are likely to be without an appreciable risk of adverse effects for specified periods of exposure. These are know as Minimum Risk Levels. The ATSDR establishes Minimum Risk Levels for three durations of inhalation or oral exposure. Durations are acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more).

Front 78

Legal standards for workplace exposures are established by what?

Back 78

Legal standards for workplace exposures are established by the Occupational Safety and Health Administration (OSHA).

Front 79

Legal standards for workplace exposures are established by the Occupational Safety and Health Administration (OSHA). What are these standards known as?

Back 79

These standards are known as Permissible Exposure Limits (PELs).

Front 80

Most OSHA PELs are for what? This is known as what?

Back 80

Most OSHA PELs are for airborne substances with allowable exposure limits averaged over an 8-hour day, 40-hour week. This is known as the Time-Weighted-Average (TWA) PEL. Adverse effects should not be encountered with repeated exposures at the TWA PEL.

Front 81

OSHA also issues ?, ?, and ?.

Back 81

OSHA also issues Short Term Exposure Limit (STELs) PELs, Ceiling Limit PELs, and PELs that carry a skin designation.

Front 82

What are PEL STELs?

Back 82

PEL STELs are concentration limits of substances in the air that a worker may be exposed to for 15 minutes without suffering adverse effects. The 15 minute STEL is usually considerably higher than the 8-hour TWA exposure level. For example, for trichloroethylene the PEL-STEL is 200 ppm whereas the PEL-TWA is 50 ppm.

Front 83

What are Ceiling Limit PELs?

Back 83

Ceiling Limit PELs are concentration limits for airborne substances that should never be exceeded.

Front 84

What is a skin designation?

Back 84

A skin designation indicates that the substance can be readily absorbed through the skin, eye or mucous membranes, and substantially contribute to the dose that a worker receives from inhalation of the substance.

Front 85

Could an occupational substance have PELs as TWA, STEL, Ceiling Limit, and a skin designation?

Back 85

Theoretically, an occupational substance could have PELs as TWA, STEL, and Ceiling Limit, and with a skin designation. This is rare however. Usually, a OSHA regulated substance will have only a PEL as a time-weighted average. About 20% of the OSHA regulated substances have PEL-STELs and only about 10% have skin notations. In a few cases, a substance may have a PEL-Ceiling but not a PEL-TWA.

Front 86

What is the 'Dangerous to Life and Health'(IDLH)?

Back 86

An occupational exposure guideline developed by the OSHA Standards Completion Program is the Immediately Dangerous to Life and Health (IDLH). This represents a maximum level that a human could be exposed to for up to 30 minutes and escape from without any serious health effects.

Front 87

The Occupational Safety and Health Administration develops workplace exposure standards known as:





Threshold Limit Values (TLVs)




Permissible Exposure Limits (PELs)




NIOSH Recommended Exposure Limits (RELs)

Back 87

The Occupational Safety and Health Administration develops workplace exposure standards known as Permissible Exposure Limits (PELs). They are OSHA-derived legal occupational exposure standards usually averaged over a normal 8-hour workday.