Pesticides in the Environment

Characteristics

Pesticide Transport and Fate

Monitoring in the Environment

Methods for Measuring Human Exposure to the Agent

Exposure Pathways

Strategies for Preventing and Controlling Pesticides


Harmful Effects of Alachlor

Dose Response of Alachlor

Absorption, Distribution and Metabolism

Sites of Toxicity

Biomarkers of Disease and Molecular Mechanisms of Action

Risk Assessment

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Risk Assessment and Risk Management

In order for a pesticide to be registered, scientific studies must be shown that it does not post excessive risks to humans or the environment. In 1969, alachlor was first registered as a selective herbicide for controlling broadleaf grasses and weeds. Today it is required that pesticides registered before November 1, 1984, be reregistered to guarantee compliance of higher safety standards. Therefore, alachlor’s status was affected, and the re-registration was signed into effect in September 1998. The pesticide re-registration process involves toxicity studies to be conducted by pesticide companies and evaluated by EPA scientists. It must be shown that unreasonable risks will not occur with the intended use and that the test results are valid.

The EPA employs a four-step process to assess human health risks:

Step 1: Hazard Identification
Step 2: Dose-Response Assessment
Step 3: Exposure Assessment
Step 4: Risk Characterization

Step 1: Hazard Identification (Toxicology)

This toxicology assessment detects the possible health risks of alachlor which can occur from a variety of different types of exposure. Most of the tests were conducted by animal studies. There were also a limited number of additional in vitro and human epidemiologic studies. The tests investigate a variety of acute, sub-chronic, chronic, developmental, and reproductive effects. There are also tests on mutagenicity and metabolism. They identify a broad assortment of effects ranging from eye and skin irritation to carcinogenicity to birth defects. LD50, NOEL, and LOEL values are determined by the acute, subchronic, and chronic tests. The reproductive tests concluded that alachlor is not likely to cause reproductive or birth defects. Alachor also does not appear to be mutagenic.

Step 2: Dose-Response Assessment

The dose-response assessment examines the relationship between the level of exposure and the resultant toxicity of the hazards. One important aspect of the dose-response assessment is the establishment of a reference dose (RfD). The RfD states the amount of the chemical, if received over a lifetime, should not cause harmful effects. The RfD of Alachlor was based on NOEL and LOEL levels from wide ranging toxicity studies. alachlor’s RfD was set at 0.01 mg/kg/day.

The rate of dermal absorption is measured to identify how these rates change at different dosages. This was done for alachlor by three different pharmacokinetics studies on Rhesus monkeys. The studies displayed the distribution and elimination of alachlor. Doses were given intravenously and applied dermally.

Further studies were conducted to identify the carcinogenicity of alachlor. Alachlor produced an increase in malignant tumors in rats as the dosage levels were increased. The Cancer Peer Review Committee thought this was enough evidence to classify it as a probable human carcinogen. The evidence of a carcinogen was apparent in the rats; but it was not proven in human studies. The tumors may be relevant to humans; however they were given to rats at very extreme levels.

The duration of exposure is important to consider. Varying durations of acute, short-term, intermediate-term, and chronic are taken into account when formulating risk assessments.

The Food Quality Protection Act has set guidelines to make certain children are not adversely affected by these allowances. Previously there had been a 10X safety factor for enhanced sensitivity in children. This factor was removed since no indication of increased susceptibility was shown.

Step 3: Exposure Assessment

Exposure to alachlor is through one of three routes: inhalation, absorption, or ingestion. Different exposure circumstances may follow one or multiple routes.

The dietary exposures from food are determined by the residues found in plants and animals. Examples of such commodities are corn, soybeans, peanuts, milk, eggs, and meat. Tolerances are set from combined residues of alachlor and its metabolites. Tolerances range from 0.02 to 3.0 ppm.

Dietary exposures from drinking water are regulated under the Safe Drinking Water Act (SDWA). The maximum contaminant level (MCL) for alachlor is 0.02 ppb. This is the highest level of alachlor permissible to be present in a public water supply. Cost analyses and treatment possibilities play a part in setting the MCL. Estimates of exposure from drinking water are determined by the following equation (for adult males):


Occupation exposures can occur in workers such as handlers, mixers, and applicators. Exposure routes are mainly by inhalation or dermal absorption. These workers face unique risks that the rest of the general population does not often face.

Before the re-registration process was completed, it was decided that alachlor would be reclassified as a restricted use pesticide due to oncogenicity and groundwater concerns. Because of this, it was unnecessary to assess alachlor on the basis of home or personal use.

Step 4: Risk Characterization

The final step in assessing risk is the process of risk characterization. It combines the toxicology studies, dose-response, and exposure assessments to generate an overall risk. This is dependent upon the likelihood of exposure and the toxicity level of alachlor. Assumptions and uncertainties are discussed, such as how the animal tests are extrapolated to man. The inconsistencies are accounted for by uncertainty factors added to the assessment.

Risk Management

After the EPA completed and reviewed the risk assessment, they felt there was sufficient data to support the reregistration of alachlor. Under the reregistration there were a number of new regulations imposed. For example, alachlor is now classified as a restricted use pesticide. Numerous measures have been taken to protect workers such as requiring long-sleeved shirts and pants, chemical resistant gloves and footwear, and goggles during certain applications. Other restrictions involve limitations on the amounts that can be sprayed in areas within certain timeframes.

References

Extoxnet Pesticide Information Profiles http://ace.ace.orst.edu/infi/extoxnet/pips/alachlor.htm

EPA, Alachlor Reregistration Eligibility Decision, 1997
www.epa.gov/oppsrrd1/REDs/0063.pdf

Alachlor Scorecard
http://www.scorecard.org/chemical-profiles/chems-profile-descriptions.tcl

Integrated Risk Information System http://www.epa.gov/iris/subst/0129.htm

Assessing Health Risks from Pesticide http://www.epa.gov/pesticides/factsheets/riskssess.htm

Consumer Factsheet on Alachlor http://www.epa.gov/safewater/dwh/c-soc/alachlor.html