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Hazard Rankings

Acute Toxicity


World Health Organization (WHO) Acute Hazard Rankings

The WHO bases its ratings on the lowest published rat oral LD50, the lethal dose (in milligrams of substance per kilogram of body weight) that kills 50% of the test animals in a standard assay. WHO gives a hazard ranking of Ia (Extremely Hazardous) to the most hazardous pesticide active ingredients. While the WHO ratings generally reflect acute toxicity, they also take into account other toxic effects such as reproductive and developmental toxicity. WHO does not evaluate the fumigants, a class of gaseous pesticides that are generally extremely hazardous, nor does it evaluate pesticides believed obsolete or discontinued, even though some of these "obsolete" pesticides are currently registered for use in the U.S.

WHO Toxicity Classification

Rat LD50 (mg of chemical per kg of body weight)

Class

Description

Solids (oral)

Liquids (oral]

Solids (dermal)

Liquids (dermal)

Ia

Extremely hazardous

5 or less

20 or less

10 or less

40 or less

Ib

Highly hazardous

5-50

20-200

10-100

40-400

II

Moderately hazardous

50-500

200-2,000

100-1,000

400-4,000

III

Slightly hazardous

over 500

over 2,000

over 1000

over 4,000

U.S. EPA Acute Toxicity Rankings

Formulated pesticide products (which often include inert ingredients) are given an acute toxicity rating by the U.S. EPA which is reflected in the warning label on the pesticide container. The U.S. EPA gives a warning label of Category 1 to the most acutely toxic pesticide products and Category 4 to the least acutely toxic pesticide products. The different toxicity categories are based on the LC50, the lethal dose (in milligrams of substance per kilogram of body weight) that kills 50% of the test animals in a standard assay. For inhalation exposures, the LC50 is used---the concentration in air in mg per liter that kills 50% of the test animals.
Active ingredients can be similarly ranked for toxicity on the basis of LD50 values. Thus, warning labels for single-active-ingredient pesticide products containing technical grade active ingredients over 90% pure can serve as a reasonable proxy for the toxicity of the active ingredient. However, many of these warning labels are not internally consistent, and different pesticide products containing essentially the same concentration of active ingredient are labeled with two or more different toxicity ratings. In this situation, the U.S. EPA acute toxicity rating for the chemical was noted as "No Consensus Value."

U.S. EPA Categories and Warning Labels

Acute Toxicity to Rats

Category

PAN Narrative Rating

Warning Label

Oral LD50(mg/kg)

Dermal LD50(mg/kg)

Inhalation LC50(mg/L)

Eye Effects

SkinEffects

1

Highly Toxic

Danger-Poison*

< 50

< 200

< 0.05

1

Highly Toxic

Danger

< 50

< 200

< 0.05

Corrosive (irreversible destruction of ocular tissue) or corneal involvement or irritation persisting for more than 21 days.

Corrosive (tissue destruction into the dermis and/or scarring)

2

Moderately Toxic

Warning

50-500

200-2,000

0.05-0.5

Corneal involvement or irritation clearing in 8-21 days

Severe irritation at 72 hours (severe erythema or edema)

3

Slightly Toxic

Caution

500-5,000

2,000-5,000

0.5-2

Corneal involvement or irritation clearing in 7 days or less

Moderate irritation at 72 hours (moderate erythema)

4

Not Acutely Toxic

None

> 5,000

> 5,000

> 2

Minimal effects clearing in less than 24 hours

Mild or slight irritation (no irritation or slight erythema)

*This signal word is used for acute systemic poisons.

Cancer Information


International Agency for Research on Cancer (IARC) Carcinogen List

A list of chemicals is maintained by IARC, an international organization that evaluates chemicals for carcinogenicity and assigns a ranking to them. The IARC system gives the following designations:

  • Group 1: Known carcinogens
  • Group 2a: Probable carcinogens
  • Group 2b: Possible carcinogens
  • Group 3: Unclassifiable because the data are incomplete or ambiguous.
  • Group 4: Probably not carcinogens

U.S. National Toxicology Program (NTP) Carcinogen List

A list of carcinogenic substances is constructed by the National Toxicology Program, the U.S. Dept. of Health and Human Services, and the Public Health Service. This list is published by the U.S. National Institutes of Health (NIH). Section 301 (b)(4) of the Public Health Service Act mandates that the Secretary of the Department of Health and Human Services (DHHS) shall publish a biennial report that contains a list of all substances:

  • which either are known to be human carcinogens or may reasonably be anticipated to be human carcinogens, and
  • to which a significant number of persons residing in the United States are exposed.

The U.S. NTP system ranks chemicals as "Known Carcinogens" or "Reasonably Anticipated to Be a Carcinogen."

U.S. EPA Office of Pesticide Programs (OPP) Carcinogen List

The U.S. EPA-OPP maintains a List of Chemicals Evaluated for Carcinogenic Potential, which classifies pesticides by their role in causing cancer in humans and laboratory animals. The process by which chemicals are ranked involves first selecting the chemicals to evaluate, than bringing together a panel of scientists who evaluate the available data and make a decision about a cancer ranking based on the weight of the evidence. The data evaluated includes both epidemiological studies on humans exposed to the chemical in the course of their daily lives, as well as studies on laboratory animals. Chemicals that have been studied extensively are more likely to have an accurate rating; however, this means that newer chemicals that have been on the market for less time may not have been studied sufficiently for scientists to conduct a complete evaluation.

U.S. EPA's classification of carcinogenicity has changed three times over the last 15 years. The categories used by U.S. EPA between 1986 and 1996 are:

Category A: Known to cause cancer in humans
Generally based on epidemiological data showing sufficient evidence to support a causal association between exposure to the substance and cancer.
Category B: Probable human carcinogen
Known to cause cancer in animals but not yet definitively shown to cause cancer in humans. Category B is further split into:

  • B1: Sufficient evidence of carcinogenicity from animal studies with limited evidence of carcinogenicity from epidemiologic studies in humans.
  • B2: Sufficient evidence of carcinogenicity from animal studies with inadequate or no data from epidemiologic studies in humans.
  • Category C: Possible human carcinogen
    The data show limited evidence of carcinogenicity in the absence of human data.
  • Category D: Not classifiable as to human carcinogenicity
    This category is for chemicals for which the data are either incomplete, inadequate or ambiguous and is labeled "not classifiable" or "cannot be determined." This category is appropriate when tumor effects or other key data are suggestive or conflicting or limited in quantity and are thus not adequate to convincingly demonstrate carcinogenic potential for humans. In general, further chemical-specific and generic research and testing are needed to be able to describe human carcinogenic potential.
  • Category E: Probably not carcinogenic, with no evidence of carcinogenicity in at least two adequate animal tests in different species in adequate epidemiologic and animal studies. This classification is based on available evidence and does not mean that the agent will not be a carcinogen under any circumstances.

The categories used by U.S. EPA between 1996 and 1999 are:

  • Known/Likely: This category of descriptors is appropriate when the available tumor effects and other key data are adequate to convincingly demonstrate carcinogenic potential for humans; it includes:
  • Agents known to be carcinogenic in humans based on either epidemiologic evidence of a combination of epidemiologic and experimental evidence, demonstrating causality between human exposure and cancer.
  • Agents that should be treated as if they were known human carcinogens, based on a combination of epidemiologic data showing a plausible causal association (not demonstrating it definitively) and strong experimental evidence.
  • Agents that are likely to produce cancer in humans due to the production or anticipated production of tumors by modes of action that are relevant or assumed to be relevant to human carcinogenicity.
  • Cannot be determined: This category of descriptors is appropriate when available tumor effects or other key data are suggestive or conflicting or limited in quantity and thus, are not adequate to convincingly demonstrate carcinogenic potential for humans. In general, further agent-specific and generic research and testing are needed to be able to describe human carcinogenic potential. The descriptor 'cannot be determined' is used with a subdescriptor that further specifies the rationale:
  • Agents whose carcinogenic potential cannot be determined, but for which there is suggestive evidence that raises concern for carcinogenic effects.
  • Agents whose carcinogenic potential cannot be determined because the existing evidence is composed of conflicting data (e.g., some evidence is suggestive of carcinogenic effects, but other equally pertinent evidence does not confirm any concern), agents whose carcinogenic potential cannot be determined because there are inadequate data to perform an assessment.
  • Agents whose carcinogenic potential cannot be determined because no data are available to perform an assessment.
  • Not likely: This is the appropriate descriptor when experimental evidence is satisfactory for deciding that there is no basis for human hazard concern, as follows (in the absence of human data suggesting a potential for cancer effects):
  • Agents not likely to be carcinogenic to humans because they have been evaluated in at least two well conducted studies in two appropriate animal species without demonstrating carcinogenic effects.
  • Agents not likely to be carcinogenic to humans because they have been appropriately evaluated in animals and show only carcinogenic effects that have been shown not to be relevant to humans (e.g., showing only effects in the male rat kidney due to accumulation of alpha(2u)-globulin).
  • Agents not likely to be carcinogenic to humans when carcinogenicity is dose or route dependent. For instance, not likely below a certain dose range (categorized as likely by another route of exposure). To qualify, agents will have been appropriately evaluated in animal studies and the only effects show a dose range or route limitation, or a route limitation is otherwise shown by empirical data.
  • Agents not likely to be carcinogenic to humans based on extensive human experience that demonstrates lack of effect (e.g., phenobarbital).

The categories used by U.S. EPA from 1999 to the present are:

  • Carcinogenic to humans: This descriptor is appropriate when there is convincing epidemiologic evidence demonstrating causality between human exposure and cancer. This descriptor is also appropriate when there is an absence of conclusive epidemiologic evidence to clearly establish a cause and effect relationship between human exposure and cancer, but there is compelling evidence of carcinogenicity in animals and mechanistic information in animals and humans demonstrating similar mode(s) of carcinogenic action. It is used when all of the following conditions are met:
  • There is evidence in a human population(s) of association of exposure to the agent with cancer, but not enough to show a causal association, and
  • There is extensive evidence of carcinogenicity, and
  • The mode(s) of carcinogenic action and associated key events have been identified in animals, and
  • The key events that precede the cancer response in animals have been observed in the human population(s) that also shows evidence of an association of exposure to the agent with cancer.
  • Likely to be carcinogenic to humans: This descriptor is appropriate when the available tumor effects and other key data are adequate to demonstrate carcinogenic potential to humans. Adequate data are within a spectrum. At one end is evidence for an association between human exposure to the agent and cancer and strong experimental evidence of carcinogenicity in animals; at the other, with no human data, the weight of experimental evidence shows animal carcinogenicity by a mode or modes of action that are relevant or assumed to be relevant to humans.
  • Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential: This descriptor is appropriate when the evidence from human or animal data is suggestive of carcinogenicity, which raises a concern for carcinogenic effects, but is judged not sufficient for a conclusion as to human carcinogenic potential. Examples of such evidence may include; a marginal increase in tumors that may be exposure-related, or evidence is observed only in a single study, or the only evidence is limited to certain high background tumors in one sex of one species. Dose-response assessment is not indicated for these agents. Further studies would be needed to determine human carcinogenic potential.
  • Data are inadequate for an assessment of human carcinogenic potential: This descriptor is used when available data are judged inadequate to perform an assessment. This includes a case when there is a lack of pertinent or useful data or when existing evidence is conflicting, e.g., some evidence is suggestive of carcinogenic effects, but other equally pertinent evidence does not confirm a concern.
  • Not likely to be carcinogenic to humans: This descriptor is used when the available data are considered robust for deciding that there is no basis for human hazard concern. The judgement may be based on:
  • Extensive human experience that demonstrates lack of carcinogenic effect (e.g., phenobarbital).
  • Animal evidence that demonstrates lack of carcinogenic effect in at least two well designed and well conducted studies in two appropriate animal species (in the absence of human data suggesting a potential for cancer effects).
  • Extensive experimental evidence showing that the only carcinogenic effects observed in animals are not considered relevant to humans (e.g., showing only effects in the male rat kidney due to accumulation of alpha-2u-globulin).
  • Evidence that carcinogenic effects are not likely by a particular route of exposure.
  • Evidence that carcinogenic effects are not anticipated below a defined dose range.

State of California Proposition 65 Carcinogen List

A list of chemicals "known to the State to cause cancer" is maintained by the State of California under the Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65). Unlike other rating systems, California does not rank chemicals for their carcinogenicity, but simply designates a chemical as a "Known" carcinogen.
The absence of a chemical on this list does not necessarily mean it is not a carcinogen. It may mean that it has not yet been evaluated by the agencies responsible.

Endocrine Disruption


Illinois EPA List

In 1997, the Illinois state EPA published a list of endocrine disrupting compounds. The list contains three categories of endocrine disrupting chemicals corresponding to the overall evidence available that the chemical is capable of disrupting the endocrine system:

  • Known: Chemicals for which strong evidence exists that endocrine-disrupting effects occur in intact animals.
  • Probable: Chemicals for which the preponderance of the evidence (in both intact animals and in bioassays) suggests that the chemical can cause disruption of the endocrine system.
  • Suspected: Chemicals lacking good evidence in intact animals or for which only assay evidence of endocrine disruption exists.

European Union (EU) Prioritization List

In December 1999, the European Commission adopted a strategy for addressing the problem of endocrine-disrupting chemicals. Part of this strategy was to establish a priority list of substances for further evaluation of their role in endocrine disruption. The list is to be used to identify substances for priority testing, once test methods become available, and to identify gaps in knowledge of the toxicity and exposure pathways.

Prioritization was based on evidence of endocrine disruption in humans or animals and on the exposure potential for the chemical based on persistence in the environment and the amount of the substance produced. The starting point of the study was a working list, compiled from the lists of suspected endocrine disrupting chemicals drawn up by various organizations as well as from an up-to-date literature search. The list contains three categories of endocrine disrupting chemicals:

  • Category 1 - evidence of endocrine disrupting activity in at least one species using intact animals;
  • Category 2 - at least some in vitro evidence of biological activity related to endocrine disruption;
  • Category 3 - no evidence of endocrine disrupting activity or no data available (#Europa.eu).

Reproductive and Developmental Toxicity


U.S. EPA Toxics Release Inventory List

In 1986, Congress passed the Emergency Planning and Community Right-To-Know Act (EPCRA) and the Pollution Prevention Act (PPA), with the intent of increasing the transparency of the use and disposal of chemicals in manufacturing, mining, and other activities. Section 313 of the EPCRA and section 6607 of the PPA required companies that release toxic materials to provide information to U.S. EPA on the identity and amounts of these toxic chemicals they are releasing to air, land and water. This information is made available to the public through U.S. EPA as the Toxics Release Inventory (TRI), providing valuable information on the release and transport of toxic chemicals in the U.S.

U.S. EPA publishes a list of chemicals that must be reported. A chemical is placed on the list if it is toxic to humans or damaging to the environment. The current TRI toxic chemical list containsThe current TRI toxic chemical list contains 581 individually listed chemicals and 30 chemical categories (including 3 delimited categories containing 58 chemicals). If the members of the three delimited categories are counted as separate chemicals then the total number of chemicals and chemical categories is 666 (i.e., 581 + 27 + 58) (#TRI Chemical List).
Toxicity categories evaluated for the TRI list of chemicals includes acute toxicity, carcinogenicity, reproductive and developmental toxicity, environmental toxicity and toxicity to organ systems including cardiovascular, liver, gastrointestinal, kidney, immune, hematological, and respiratory systems.

California Proposition 65 List

Pesticides determined by the state of California to cause reproductive and developmental harm, e.g., birth defects, infertility, sterility and impairment of normal growth and development. A list of chemicals "known to the State to cause reproductive and developmental toxicity" is maintained by the State of California under the Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65).

The absence of a chemical on this list does not necessarily mean it is not a reproductive or developmental toxicant. It may mean that it has not yet been evaluated by the agencies responsible. More detail is given in the "About the Data" section.

References


Main reference is : PANNA - Pesticide Action Network North America

Other:


U. S. EPA. Environmental Protection Agency. Toxics Release Inventory (TRI) Program. Accessed 12/3/2010.


European Commission. Environment. Chemicals. Endocrine Disrupters. Accessed 12/3/2010.

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