Introduction

This guideline provides an explanation of the data requirements for safety evaluations of fertilizers, soil supplements and livestock feed. It is to be used in conjunction with Trade Memorandum T-4-113 for fertilizer and soil supplements and with Trade Memorandum T-3-141 (Supplement) for livestock feeds.

We have attempted to make these notes useful to those who are not necessarily trained in science or toxicology, but who wish to obtain a general understanding of the data requirements. A listing of standard protocols used to develop the technical information is also provided for your convenience.

If you have any questions, please contact:

Canadian Food Inspection Agency
Fertilizer Section
Plant Production Division
2 Constellation Crescent
Ottawa, Ontario
Canada
K1A 0Y9
Tel:  613 221-7519
Fax: 613 228-4552;

or by email at fertilizer@inspection.gc.ca. 

Table of Contents

Introduction

1. Identification and Use of the Product
a) Name and Synonyms
b) Use Patterns
c) Feed Additive Use Patterns
d) Species of Intended Use
e) Unit Amount
f) Product Label
g) Material Safety Data Sheet (MSDS) for Product or Ingredients
h) Outline of Manufacture

2. Chemical Components Including Impurities
a) Name and Synonyms
b) Chemical Abstract Service Number
c) Chemical Formula (Molecular and Structural)
d) Concentrations in the Finished Product
e) Criteria for Chemical Identity and Purity
f) Estimated Shelf Life

3. Method(s) of Analysis, Recovery and Detection Limit Data for the Analyses

4. Physicochemical Data
a) Molecular Weight
b) Physical State
c) Appearance
d) Particle Size
e) Colour and Odour
f) Olfactory Detection Limit
g) Density/Specific Gravity
h) Refractive Index
i) Melting Point
j) Boiling Point
k) Flash Point
l) Auto-Ignition Point
m) Vapour Pressure
n) Vapour Density
o) Henry's Law Constant
p) pH
q) Solubility
r) Octanol-Water Partition Coefficient
s) Dissociation Constant
t) Incompatibility
u) Polymerization

5. Mammalian Toxicological Data
a) Rate and Degree of Absorption
b) Distribution, Metabolism and Excretion Data
c) Acute Toxicity
i) Acute Median Lethality
ii) Skin/Eye Irritation
iii) Skin Sensitization
d) Mutagenicity
e) Short-Term Toxicity
f) Teratogenicity
g) Developmental Toxicity
h) Reproductive Toxicity
i) Carcinogenicity
j) Epidemiological Studies
k) Chemical Interaction

6. Suggested Maximum Residue Limit (MRL) or Tolerance

7. Human Exposure Data and Exposure Estimation
a) Major Routes of Exposure
b) Amount of Product Handled by Workers and Consumers
c) Frequency and Duration of Exposure
d) Exposure Concentrations
e) Exposure Studies

8. Specifics for Food Plant Usage
a) Crop Identification
b) Rates, Timing Intervals to Harvest
c) Plant Metabolism Data
d) Product, Metabolite and/or Contaminant Residue Studies
e) Phytotoxicity
f) Analytical Methods for Metabolism and Residue Studies

9. Livestock Metabolic Fate and Residue Studies
a) Metabolic Fate Studies
b) Residue Studies for the Parent Compound and its Possible Metabolites
c) Excretion Data

10. Environmental Fate and Effects
a) Vapour Pressure and Volatilization
b) Dissociation Constant
c) Hydrolysis
d) Photodegradation
e) Solubility in Water
f) Henry's Law Constant
g) Octanol-Water Partition Coefficient
h) Adsorption-Desorption
i) Leaching
j) Biotransformation in Soil
k) Biotransformation in Aquatic Systems
l) Biochemical Oxygen Demand
m) Toxicity to Aquatic Organisms
n) Toxicity to Soil Organisms
o) Toxicity to Birds and Mammals
p) Toxicity to Wildlife

11. Bibliography of Protocols, Test Guidelines, Reference Materials and Services

1. IDENTIFICATION AND USE OF THE PRODUCT

a) Name and Synonyms:

The name of the product as it appears on the product label or shipping bill.

Commonly used alternates or acronyms, including names used in other countries, most common chemical name, a botanical or species identification, etc.

b) Use Patterns:

This describes the intended use of the product. The type of information required includes:
- mixing information if used in conjunction with other products;
- suggested rates of application;
- times, frequency and methods of application;
- recommended safety measures;
- distribution, storage, and handling information;
- recommended emergency measures;
- strategies for re-use, resale or disposal of unused product.

The Use Pattern should clearly specify whether the product will be used in food or feed production and whether it will be used indoors or outdoors, contained or uncontained, etc.

c) Feed Additive Use Patterns:

For feed additives, describe how the product is intended to be used in detail, including suggested rates and timing of feeding, intervals of feeding, and any "withdrawal times," (when product use should be reduced or discontinued).

d) Species of Intended Use:

Identify all animal or plant species and soil types for which the product is intended (if not described under Use patterns).

e) Unit Amount:

How and in what quantities is the product to be sold, transported and stored? (i.e., 50 L metal drum, 20 kg plastic-lined canvas sack, etc.)

f) Product Label:

A copy of the product label (if applicable) or bill of lading conforming to the appropriate Regulations must be provided.

g) Material Safety Data Sheet (MSDS) for Product and Ingredients:

An MSDS is a comprehensive technical bulletin containing detailed information on a substance or product. It is a basic source of information for preliminary safety evaluations identifying points (such as possible contaminants) which may need to be examined in greater detail. An MSDS should also provide a detailed explanation of precautions and protective measures. The Workplace Hazardous Materials Information System (WHMIS) provides criteria for developing an MSDS.

h) Outline of Manufacture:

A general description of the production and formulation processes, identifying raw materials, chemical reactions, techniques and any other parameters which may influence the specifications, hence quality or safety of a product. This will serve as background information relating to product purity and any recycled materials (eg., by-products and wastes) used in manufacturing or formulating the end-product.

A flow-chart diagram accompanying the description is preferred.

2. CHEMICAL COMPONENTS INCLUDING IMPURITIES

a) Name and Synonyms:

The exact chemical name and synonyms of all ingredients, including significant contaminants or impurities should be listed. For substances which need to be described by the reaction producing them (UVCBs), see CEPA Guidelines, sec 4, and Appendix III.

Blalock et al
CAS or IUPAC nomenclature rules
USCFR 40: 799

b) Chemical Abstract Service Number (CAS No.):

An identification number is assigned by the Chemical Abstracts Service (CAS) to differentiate between known chemicals. This is a useful reference when searching for technical information and should be provided for each ingredient.

CEPA Guidelines, sec 4, Appendix IV
C.A.S. (see bibliography)

c) Chemical Formula (Molecular and Structural):

The molecular formula identifies the basic elements (atoms) of molecules. A structural formula is a diagram of the bonds between atoms. Comparing these with the formulae of substances whose properties are known is useful in anticipating hazards of substances which have not themselves been tested. Where isomeric mixtures exist, (closely related chemical variants), the ratio of isomers should be included, since this may affect toxicity. For polymers, (long chains of molecules), the structural formulae should show the repeating unit(s), along with an identification of links and cross-links.

CEPA Guidelines, sec 4, Appendix VI.
FDA Principles, Appendix 1
CEPA Guidelines, 4.1.4

d) Concentrations in the Finished Product:

The amount of all ingredients in the commercial product should be expressed as a percent by weight or by parts per million (ppm).

e) Criteria for Chemical Identity and Purity:

The exact formulation of a particular product may vary, depending upon the manufacturer. A precise description of ingredients including contaminants is needed to properly assess product safety (for example, a nuclear magnetic resonance (NMR) spectrum, or a gas chromatography (GC) profile).

EPA PAG (Product chemistry)

f) Estimated Shelf Life:

This is the length of time the product can be stored without alterations to its chemical/biological integrity. This includes not only times under ideal conditions, but a description of the factors affecting shelf life, what happens when the product degrades or decays, how one can tell, whether this creates a particular hazard, and how the manufacturer has substantiated its estimation of shelf life.

Charlambous, G The Shelf Life of Food and Beverages
ASTM F 1104, F 1105

3. METHOD(S) OF ANALYSIS, RECOVERY, AND DETECTION LIMIT DATA FOR THE ANALYSES

An acceptable test method for the analysis of the proposed product must be provided. This method must establish statistically relevant recovery and detection limits and must allow third-party technicians to identify and quantify the active ingredients. For specific requirements of analytical methods, please see "Good Laboratory Practices Protocol for Fertilizer and Supplement Registration" or Trade Memorandum T-3-151 for feed ingredients.

ASTM (For statistical standards)
AOAC Methods of Analysis
EPA PAG: (Requirements for Analytical Methods)
Stahr, HM Analytical Toxicology Methods Manual
OJEC Council Directives
Wernimont, GT Use of Statistics to Develop and Evaluate Analytical Methods

4. PHYSICOCHEMICAL DATA

Physicochemical data is used to identify and differentiate between substances or products and to assist in predicting or determining the behaviour of substances in the human body, other organisms or the environment. Please note the reference protocols associated with each data point. Unless otherwise specified, these data points apply to the technical grade formulation of the substance and not to an analytically purified sample.

a) Molecular weight:

Every chemical has a characteristic molecular "weight" determined by the elements or atoms that make it up. In the case of polymers, (molecules composed of atomic "chains" of varying length), an average is given to describe molecular weight and testing is performed on the lowest number-average composition.

CEPA Guidelines, 4.2.2.1, (Sec 4, Appendix VI, for polymers)

b) Physical state:

This indicates whether a substance or product is solid, liquid or gaseous at room temperature.

c) Appearance:

This describes the form of the product, such as a granular solid, gelatinous liquid, or a fine powder.

d) Particle Size:

If the substance is solid, what is its average particle size? What is the range of particle sizes, and their proportion of distribution? This property may be a significant factor determining the distribution and uptake of a substance, for example, whether it is taken up by organisms or inhaled into human lungs.

OECD Test Guidelines, 110.
US CFR 40: 796.1520

e) Colour and Odour:

Include this description for the chemical ingredients as well as for the formulated product, including any noted variations.

f) Olfactory Detection Limit:

This is the minimum concentration (e.g.., parts per million by volume in air), at which one can identify the substance by smell. This is important in determining whether or not smell can serve as an appropriate warning of the presence of the substance.

g) Density/Specific Gravity:

For solids, this is measured as mass per volume (i.e., g/mL). For liquids, specific gravity compares density to that of water, which is assigned a value of 1,(i.e., 2.0 is twice as dense as water, 0.50 is half as dense). These measurements are used in several ways, such as when predicting the behaviour of a substance in the environment.

OECD Test Guidelines, 109.
ASTM E 12

h) Refractive Index:

The speed of light changes as light passes from one medium to another, causing it to "bend," (as objects partially inserted into water look bent.) This property varies from one substance to another and is sometimes useful in identifying substances using a simple, accurate technique.

ASTM D 1218, D 1747

i) Melting Point:

The temperature, at a specified pressure, at which a solid becomes liquid. Some chemicals break down or undergo chemical reaction before reaching their melting point; details of this should be identified.

OECD Test Guidelines, 102.

j) Boiling Point:

The temperature, at a specified pressure, at which a liquid becomes a gas. Some chemicals break down or undergo chemical reaction before reaching their boiling point; details of this should be identified.

OECD Test Guidelines, 103.
US CFR 40: 796.1220

k) Flash Point:

The minimum temperature at which a liquid gives off enough flammable vapours that these will ignite on contact with a flame or spark. This has obvious implications for worker safety during handling and storage.

ASTM E 502-84

l) Auto-Ignition Point:

The minimum temperature at which a flammable liquid will ignite spontaneously without an ignition source. Again, an important safety parameter.

ASTM G 72-82, E 659-78

m) Vapour Pressure:

This is a measure of a liquid's ability to evaporate, or give off vapours at specific temperatures. Usually expressed in millimetres of mercury (mmHg), it is a crucial indicator of the behaviour of a liquid product, indicating, for example, whether it will tend to escape to the atmosphere or remain in soil.

AOAC Methods of Analysis OECD Test Guidelines, 104 USCFR 40: 796.1950 ASTM E 1194-87

n) Vapour Density:

A comparison between the mass of a gas and that of dry air which is assigned a value of 1, (i.e., 2.0 is twice as dense as air, 0.50 is half as dense). This is another important indicator of how a substance will behave. Less dense gases tend to rise and are quickly transported throughout the environment; heavier gases remain closer to the ground and dissipate less rapidly.

ASTM E 12

o) Henry's Law Constant:

This is a measure of the solubility of a gas in liquid. It is indicative of a substance's tendency to move from water to air or vice-versa.

p) pH:

Indicates if a substance is acidic, alkaline or neutral and how strong an acid or base it is. Besides measuring potential corrosivity, pH can have a major effect on the interactions of a substance with living organisms, such as the degree to which it is absorbed or taken up.

ASTM E 70 (general) ASTM D 5015, D 4980, E 301, D 2976, D 651, D 4972, D 1067, D 3875, D 1293 (specific chemicals/matrices)

q) Solubility:

i) in Water: This measures the amount of a substance that will dissolve in water at a given temperature. Since water supports life and since many chemicals dissolve in water to a significant degree, it is often the route by which chemicals are taken up by organisms. It is also used in predictions of environmental fate of substances.

OECD Test Guidelines, 105
US CFR 40: 796.1840, 796.1860
ASTM E 1148-87

ii) in Other Solvents: This measures the amount of a substance that will dissolve in solvents other than water. This provides a guide for choosing a solvent to extract a chemical from organic tissue or soil for further analysis, for instance.

OECD Test Guidelines, 116 ASTM D 1696

r) Octanol-Water Partition Coefficient:

This measures the tendency of a substance to separate, either into organic solvents or into water. A fundamental toxicological data point, it is used in predicting whether a substance may build up in the fatty tissues of an organism and in predicting its tendency to adhere to soil particles.

OECD Test Guidelines, 107, 117
US CFR 40: 796.1550; 796.1570; 796.1720
AOAC
ASTM E 1147-87, and E 1022 (bioconcentration)

s) Dissociation Constant:

Dissociation is a specific type of chemical decomposition in which a molecule breaks up into charged particles called ions. Ions, in turn, are often involved in further chemical reactions and may be absorbed or distributed at a different rate. For given conditions, the rate of dissociation expressed as a value (the dissociation constant) is constant.

OECD Test Guidelines, 112

t) Incompatibility:

Some substances react violently or explosively with other substances. If the formulated product or any of its ingredients should not come in contact with certain substances, this must be reported.

u) Polymerization:

Some substances may spontaneously polymerize (form long molecular chains) under certain conditions. Many of these reactions give off dangerous or explosive amounts of heat. Any such substances contained in the formulated product must be identified along with a description of conditions under which spontaneous polymerization is known to occur.

5. MAMMALIAN TOXICOLOGICAL DATA

In order to assess the potentially harmful effects of substances on mammals, information from laboratory-scale tests is necessary. The type of toxicity data generally considered is outlined below.

FDA Toxicological Principles [Core and current standards]
EPA Health Effects Test Guidelines
EPA Short-term Tests for Health & Environmental Effects
NTP Specifications

a) Rate and Degree of Absorption:

For each route by which a substance can be taken into the body (oral, dermal, respiratory, etc.), absorption tests determine how extensively and how rapidly it can be absorbed.

b) Distribution, Metabolism and Elimination Data:

These tests describe the fate of a chemical once it is absorbed into the body.

Where does it go? Does it accumulate? How is it broken down or transformed? By what route and how quickly is it eliminated? This information provides an indication of an organism's ability to tolerate short- or long-term exposure, either at high or low concentrations. It is useful information in designing toxicity tests, eg., in dose selection. It also aids in extrapolating animal data to human conditions.

EPA Test Guidelines, and EPA PAG: Metabolism
OECD Test Guidelines, 417
US CFR 40: 798.7100

c) Acute Toxicity:

Acute exposure tests examine the effects of short-term, single exposures to high concentrations of a substance. Exposures in these tests are typically 24 hours or less, with effects being monitored for two weeks. This is the first step in establishing the toxic potential of substances. This is especially useful for establishing the crucial relationship between the dose and the response, for ranking substances according to their relative acute toxicity and for classification and precautionary label statements. Acute toxicity data is used to obtain preliminary information on specific toxic effects of substances and how these may be produced (mode of action). Some specialized acute tests are described below.

OECD Test Guidelines, 401, 402, 403, 418, 420
EPA Guidelines, (acute exposure)
US CFR 40: 798.1150; 798.1175; 798.2450; 798.2650; 798.2675

i) Acute Median Lethality: The concentration of a substance which, when administered once to a group of animals for a short time, will cause death in half of the animals. This is expressed as an LD50, (lethal dose, in mg/kg of body weight), or LC50, (lethal concentration, in parts per million).

FDA Principles, acute oral LD₅₀

ii) Skin/Eye Irritation: This determines if a substance has the potential to cause irritation or cell death (necrosis) when in contact with the skin or eyes.

OECD Test Guidelines, 404, 405
EPA Guidelines, and EPA PAG: Dermal & eye irritation
US CFR 40: 798.1100; 798.2250; 798.4470; 798.4500
ASTM F 719

iii) Skin Sensitization: Property of being able to "sensitize" organisms: Organisms may become more sensitive to a substance after an initial exposure and develop allergic reactions in subsequent exposures.

OECD Test Guidelines, 406
EPA Guidelines, and EPA PAG: Dermal sensitization
US CFR 40: 798.4100
ASTM F 720

d) Mutagenicity:

A screening test in determining a substance's potential for causing genetic mutations which may lead to cancer or malformations in offspring. At least two types of tests are performed, conventionally one with bacteria and one with mammalian cell cultures. It is also necessary to perform tests with and without "activation," that is, to determine if interaction with metabolic processes in the body makes a substance "mutagenic".

OECD Test Guidelines, 471 - 485
EPA Guidelines, section III;
EPA PAG: Mutagenicity US CFR 40: Subpart F (genetic toxicity), 798.5100 - 798.5955

e) Short-Term Toxicity:

Short-term toxicity studies involve repeated exposure to substances over a longer (more typical) time frame. They are useful for detecting most longer-term adverse health effects, for establishing a threshold level at which no effects are observed (NOEL), for establishing possible cumulative effects of exposure, species and other types of variation and for suggesting appropriate conditions for chronic tests, if deemed necessary. A 90-day oral study is typical, but inhalation and dermal studies may be more appropriate, depending on typical human exposure conditions.

OECD Test Guidelines, 407 - 413, 419
EPA Guidelines, (sub-chronic exposure)
FDA Principles, (short-term continuous; sub-chronic oral)

f) Teratogenicity:

These types of tests explore the possibility of birth defects resulting from parental or placental exposure to chemicals.

OECD Test Guidelines, 414
EPA Guidelines, (teratogenicity)
FDA Principles, (teratogenicity in rodents)

g) Developmental Toxicity:

These tests examine adverse effects during the lifetime of an organism prior to conception, during pre-natal development or until puberty, resulting from exposure of either parent to a substance.

US CFR 40: 798.4350, 798.4420, 798.4900

h) Reproductive Toxicity:

Adverse effects of substances on male or female reproductive systems and capacity (from mating through lactation).

OECD Test Guidelines, 415, 416
EPA Guidelines, (reproductive/fertility effects)
FDA Principles, (three generation reproduction toxicity)
US CFR 40: 798.4700

i) Carcinogenicity:

Where indicated by earlier tests or other data, a substance will be examined for its ability to induce cancer (tumours) in animals. Tests are typically conducted over a major portion of the animal's life span, often combined with chronic toxicity tests.

OECD Test Guidelines, 451, 452, 453
EPA Guidelines, and EPA PAG: Oncogenicity
FDA Principles, (carcinogenicity, combined chronic/cancer)
US CFR 40: 798.3300, 798.3320

j) Epidemiological Studies:

This type of study contains a compilation and analysis of information on humans who have been occupationally or accidentally exposed to a substance.

k) Chemical Interaction:

The toxic effect of a substance can sometimes be altered — either increased, decreased, or changed entirely — by interactions with other substances. A toxin may be rendered harmless by another, or its effect may be magnified many times. Data to identify and measure the significance of such interactions improves the hazard assessment for the substance.

6. SUGGESTED MAXIMUM RESIDUE LIMIT (MRL) OR TOLERANCE

An MRL is to be suggested, based on an evaluation of information, such as mammalian toxicity data, dietary intake estimates and livestock metabolism data.

This criteria governs the concentration of a chemical that may build up in the tissues of plants or livestock without causing harm to the plant or animal, or to the humans that consume their products.

7. HUMAN EXPOSURE DATA AND EXPOSURE ESTIMATION

The following information is important in assessing the degree of exposure of workers and users to particular substances.

a) Major Routes of Exposure:

Human exposure to a substance depends, in part, on how it can be taken up by the body, whether via the respiratory route, skin absorption, oral ingestion, etc. Based on the properties of a product's ingredients, its formulation and methods of use, how might users be exposed?

b) Amount of Product Handled by Workers and Consumers:

What is the total quantity of product that would typically be used in a given application cycle (eg., 50 litres/day)?

c) Frequency and Duration of Exposure:

How often and how many times will the product normally be used? How long is the product used each time?

d) Exposure Concentrations:

How concentrated is the product when transported, stored and actually used? Is it diluted before use? Include references to intermediate preparation steps, such as mixing.

e) Exposure Studies:

Include all data on human exposure, uptake into the body, and medical studies of workers who have been exposed to the product over long periods of time. In some cases exposure studies may have to be conducted to establish how much absorption into and distribution through the body takes place with intended conditions of use.

EPA PAG, Subdivision U; "Application Exposure Monitoring"

8. SPECIFICS FOR FOOD PLANT USAGE

The following information is required to assess the safety of substances to be used in conjunction with food or feed crops.

EPA Test Guidelines: Chemical Fate
AOAC Methods of Analysis
AACC Approved Methods of the American Association of Cereal Chemists

a) Crop Identification:

This indicates the specific agricultural crop(s) on which the product is intended to be used.

b) Rates, Timing, Intervals to Harvest:

This section is to specify exactly how a product will be used and applied, including the rates of application, times at which the product is to be used and the intervals between application and harvest. These are important in determining whether it or its break-down products will remain in a crop at the time of harvest or when consumed by animals or humans. This information is required for each crop.

c) Plant Metabolism Data:

This information describes the fate of a substance in the plant; how it is broken down; what is the break-down product; to what extent does it break down; and at what rate. This study should include the levels and identities of the resulting breakdown products.

WHO/FAO Guidelines to CODEX
EPA PAG, Subdivision O

d) Product, Metabolite and/or Contaminant Residue Studies:

These tests determine the amount of parent substances, contaminants or their break-down products which remain as residues in a particular crop at harvest or when consumed. This is a most important step in establishing the potential exposure of livestock or humans through the food chain. Residue studies are performed using recommended crops and rates, timing, and intervals of harvest.

WHO/FAO Guidelines to CODEX
EPA PAG, Subdivision O

e) Phytotoxicity:

It is possible that one characteristic, such as germination, be improved at the expense of another, such as yield. Plant toxicity or phytotoxicity tests investigate these possibilities.

EPA PAG, (Non-target plants)
OECD Test Guidelines, 208

f) Analytical Methods for Metabolism and Residue Studies:

The submitted data must be accompanied by a description of the analytical methods upon which it is based. This will enable us to evaluate the accuracy and usefulness of the data. Recovery and detection limits should be included.

AOAC Methods of Analysis
USFDA Macroanalytical Procedures Manual

9. LIVESTOCK METABOLIC FATE AND RESIDUE STUDIES

Mammalian toxicity data derived from tests on mice and rats offer limited information on the risk of a particular substance to several livestock species. The following data requirements involve direct testing with livestock and apply to products the livestock are likely to be exposed to via their feed.

FDA Animal Drug Analytical Manual
OJEC Council Directive
Stahr HM Analytical Toxicology Methods Manual
USFDA Drug Analytical Manual
USFDA General Principles for Evaluating the Safety of Compounds Used in Food-Producing Animals
WHO Guidelines for the Study of Dietary Intakes of Chemical Contaminants

a) Metabolic Fate Studies:

These tests describe exactly what happens to a substance once it is ingested by livestock. How is it absorbed, and how quickly? How is it distributed throughout the body and how quickly? How is it broken down, and what are the resultant metabolites (by-products)? By what route is the substance and its metabolites eliminated from the body, and at what rate? What is their "half-life?". Appropriate methods for the recovery and analysis of the substance and its metabolites in animal tissues should be included. Detection limits of such methods must be stated.

AOAC Methods of Analysis
EPA PAG: Metabolism: Food animals

Livestock feeding studies

b) Residue Studies for the Parent Compound and its Possible Metabolites:

Residues in livestock tissue have the potential to enter the human food chain. Thus, it is important to determine how much of a substance actually remains in exposed animals and in which tissues it occurs. This data requirement should also include statistically significant analytical techniques for recovery and detection limits in animal tissues.

AOAC Methods of Analysis.

c) Elimination Data:

The ability of an organism to break down and eliminate a substance is a major consideration in evaluating the hazards of a substance. Elimination data provides a quantitative determination of this ability and indicates how effectively livestock can deplete a chemical.

AOAC Methods of Analysis

10. ENVIRONMENTAL FATE AND EFFECTS

The following data requirements, in combination with the physicochemical data, form the basis for predicting or determining which parts of the environment will be "exposed" to a substance following its release (or the release of its break-down products) and how the organisms therein may be affected.

EPA Test Guidelines: Environmental Effects

a) Vapour Pressure and Volatilization:

This is a measure of a liquid's ability to evaporate or give off vapours at specific temperatures. Usually expressed in millimetres of mercury (mmHg), it is a crucial indicator of the behaviour of a liquid product, for example, whether it will escape to the atmosphere or remain in soil.

AOAC Methods of Analysis
OECD Test Guidelines, 104
US CFR 40: 796.1950
ASTM E 1194-87

b) Dissociation Constant:

Dissociation is a specific type of chemical decomposition in which a molecule breaks up into charged particles called ions. Ions, in turn are often involved in further chemical reactions and may be absorbed or distributed at a different rate. For given conditions, the rate of dissociation expressed as a value (the dissociation constant) is constant. This can indicate how reactive the chemical may be.

OECD Test Guidelines, 112

c) Hydrolysis:

One of the main ways in which substances break down in the environment is by splitting through combination with water molecules. The extent to which this reaction may take place under normal conditions and the by-products of this type of reaction should be described.

OECD Test Guidelines, 111
US CFR 40: 796.3500, 796.3510
AOAC Methods of Analysis ASTM E 895-82
EPA PAG, (hydrolysis)

d) Photodegradation:

Another important way in which substances are broken down is by interaction with light. Tests are used to determine the potential for such degradation as well as the substance's break-down products following this type of reaction.

US CFR 40: 796.3700, 796.3780, 796.3800, 796.1050
AOAC Methods of Analysis
ASTM E 896-87
EPA PAG, (photolysis)
OECD Test Guidelines, 101 (UV-VIS Absorption Spectra)

e) Solubility in Water:

This measures the amount of a substance that will dissolve in water at a given temperature. Since water supports life and since many chemicals dissolve in water to a significant degree, it is often the route by which chemicals are taken up by organisms. It is also used in predictions of environmental fate of substances.

OECD Test Guidelines, 105.
US CFR 40: 796.1840, 796.1860
ASTM E 1148-87

f) Henry's Law Constant:

This is a measure of the solubility of a gas in liquid. It is indicative of a substance's tendency to move from water to air or vice-versa.

g) Octanol-Water Partition Coefficient:

This measures the tendency of a substance to separate, either into organic solvents or into water. A fundamental toxicological data point, it is used in predicting whether a substance may build up in the fatty tissues of an organism, and in predicting its tendency to adhere to soil particles.

OECD Test Guidelines, 107, 117 305 (bioaccumulation)
US CFR 40: 796.1550, 796.1570, 796.1720
AOAC Methods of Analysis
ASTM E 1147-87, and E 1022 (bioconcentration)

h) Adsorption-Desorption:

The ability of a substance to adsorb or become "attached" to and then desorb or detach from other particles or molecules — such as soil — affects how quickly it may move through, or how long it may remain in a particular environment.

OECD Test Guidelines, 106
US CFR 40: 796.2750
AOAC Methods of Analysis
ASTM E 1195-87
EPA PAG, (Adsorption/desorption)

i) Leaching:

This type of study establishes the potential for substances to move through different types of soil, usually under the influence of water movement. This helps to predict whether land-applied substances will reach ground water.

US CFR40: 796.2700
AOAC Methods of Analysis

j) Biotransformation in Soil:

Some substances undergo changes as a result of transformation by microorganisms, i.e., "biodegradation". These tests determine the potential for biodegradation and the break-down products which result from biodegradation. Data for both aerobic and anaerobic conditions (in the presence or absence of oxygen) are useful because different microorganisms are involved in each case and both conditions are found in the environment.

OECD Test Guidelines, 304.
AOAC Methods of Analysis

k) Biotransformation in Aquatic Systems:

As with soil biotransformation, substances may be transformed by the microbial reactions in an aquatic environment. Data for aerobic and anaerobic conditions should again be supplied.

OECD Test Guidelines, 301, 302, 306
US CFR 40: 796.3100 - 796.3480
AOAC Methods of Analysis
ASTM E 1279-89, E 1196-87

l) Biochemical Oxygen Demand:

The quantity of oxygen required by microorganisms to oxidize organic compounds in a water sample. Results are measured in mg of oxygen per litre or per gram of compound. Organic contaminants can impair water quality by reducing oxygen levels which in turn adversely affects aquatic organisms.

ASTM D 4478-85, D 888

m) Toxicity to Aquatic Organisms:

It is important to establish the adverse effects of substances on aquatic organisms. Often, the mechanisms of these effects are unique to aquatic environments and toxicity cannot be predicted using laboratory mammals. Also, the repercussions of disturbing organisms toward the bottom of the food chain can be very serious to the entire ecosystem.

OECD Test Guidelines, 201, 202, 203, 204, 210
ENV CAN Guidelines, SPE 1 RM/ 9,10,11,13,14,21 and 22.
US CFR 40: 797 subpart B, (Aquatic Guidelines), 797.1050 through 797.1970, 797.3050, and 797.3100
ENV CAN Analytical Methods Manual
ASTM E 1366-91
ASTM (Guides for aquatic toxicity)
EPA PAG, (Wildlife aquatic organisms)

n) Toxicity to Soil Organisms:

The adverse effects of substances on soil organisms is important because the long-term health of agricultural soils can be compromised by disturbing their populations.

OECD Test Guidelines, 207 (earthworm)
US CFR 40: 797.3700
ASTM E 1197-87

o) Toxicity to Birds:

The adverse effect of substances on birds can be important.

Birds may be more susceptible to the adverse effects of chemicals than laboratory animals. This difference in tolerance is partly due to differing environmental stresses and conditions as well as to metabolic and behavioral differences between organisms.

OECD Test Guidelines, 205, 206
US CFR 40: 797.2050, 797.2130, 797.2150, 797.2175

p) Toxicity to Wildlife:

These toxicity tests are valuable for indicating the adverse effects a chemical will have on animals under actual environmental conditions.

EPA PAG, (Wildlife aquatic organisms, Wild mammal toxicity)

11. BIBLIOGRAPHY OF PROTOCOLS, TEST GUIDELINES, REFERENCE MATERIALS AND SERVICES