Pesticides in the Environment

Characteristics

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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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Dose Response Assessment (Alachlor)

The table 1 shows the results of alachlor dose response assessments evaluated by EPA.

Table 1. The alachlor assessment review (EPA, 1997)

Assessment Exposure Route NOEL for Use in Estimating Risk
Acute Dietary Not required

No evidence of significant toxicity from a one day or single event exposure by the oral route

Chronic
(non-carcinogenic)
Dietary (food and water) RFD+0.01mg/kg/day
Short-term
Occupational
Dermal + Inhalation NOEL+150 mg/kg/day
MOE Approach
Carcinogenic
Dietary (food and water) NOEL=0.5mg/kg/day (nasal)
NOEL=14mg/kg/day (stomach)
Q1* Approach
Carcinogenic
Dietary (food and water) Q1*=0.08 (mg/kg/day)-1

Non-carcinogenic Endpoints

Reference Dose (RfD) (EPA, 1997)

An RfD represents the quantity of a substance which if absorbed on a daily basis over a lifetime, is not to pose significant risk of adverse health effects.


At that time, the RfD was based on a NOAEL of 1 mg/kg/day in a one year chronic dog study. The NOAEL for increased hemosiderosis in liver and spleen represents the highest NOAEL for non-carcinogenic effects in laboratory animals. An uncertainty factor (UF) of 100 was used to account for interspecies and intraspecies variability and was applied in accordance with EPA guidelines for use of a NOAEL from animal study for risk assessment.

DWEL (Drinking Water Equivalent Level) (OEHHA, 1997)

A DWEL is a medium-specific lifetime exposure level, assuming 100% exposure from that medium, at which adverse, non-carcinogenic health effects would not be expected to occur.


In order to calculate of the DWEL, the body weight of an adult male (70kg) and the volume of water consumption for an adult of 2L/day were assumed in the calculation of the DWEL.

Carcinogenic Endpoints

Alachlor has been evaluated for carcinogenic activity in rats and mice. In 1986, the EPA’s Cancer Peer Review Committee concluded that the available data was sufficient for a B2 classification, probable human carcinogen. After several reviews and, in accordance with the 1996 EPA proposed Guidelines for Carcinogen Risk Assessment, alachlor was classified as “likely” to be a human carcinogen at high doses, but “not likely” at low doses.

This conclusion was based on increased incidences of malignant and combined benign/malignant multiple tumor types in both sexes of the Long Evans rat. These tumors occurred mainly at higher doses and a similar mechanism for nasal tumor production is present in humans.

Based on many studies reviewed by agency scientists, as well as an external peer review panel, it was agreed that a margin of exposure (MOE) approach should be used for the risk assessment.

The MOE approach is indicative of a non-linear approach and reflects the assumption that there is an exposure dose below which tumor formation is not likely to occur (threshold model).The Q1* approach is indicative of a linear approach and reflects the assumption that any exposure to alachlor could cause cancer (non-threshold model).

The scientific validity of the MOE approach has been documented but the policy and appropriateness of using this approach in regulatory decision making have not yet been fully developed by the EPA. For now, the regulatory decision for alachlor will be based on both the Q1* approach and the MOE approach for the evaluation of carcinogenic potential (EPA, 1997).

A low dose extrapolation model was applied to the animal data to the animal data to calculate the Carcinogenic Slope Factor (CSF). The Q1* was calculated to be 0.08(mg/kg/day)-1 as a CSF of alachlor. The MOE for the nasal tumors should be determined with 0.5 mg/kg/day as the “point of departure (POD)” as no tumor response was seen at this dose level. The MOE for the stomach tumors should be determined with 14 mg/kg/day as the “POD”. Thyroid tumors were observed only at an excessive dose. Therefore, no “POD” was determined (EPA 1997).

References

EPA, Alachlor: Reregistration Eligibility Decision (1997)

California Office of Environmental Health Hazard Assessment (OEHHA): ALACHLOR in Drinking Water (1997)