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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Absorption, Distribution, Metabolism

Human exposure to alachlor occurs through ingestion (swallowing), inhalation (breathing), and dermal contact (contact with the skin). The amount of alachlor that the body absorbs is dependent upon the exposure pathway. After alachlor is absorbed into the body, it then travels to different locations in the body. This is known as distribution. Metabolism describes how the body changes the alachlor that is in the system when it is transported to different places in the body. When a chemical is metabolized by the body the products that are formed may be as toxic, less toxic, or more toxic than the original chemical.

Dermal Absorption

The amount of alachlor that can be absorbed by the skin once it comes into contact with it can depend on several factors. The first consideration is what form the alachlor is in upon contact, solid or liquid. Second, one should consider the area of skin that is exposed to the pesticide as the skins ability to absorb changes depending upon its’ thickness and other properties. Third, it has been shown that the formulation of different pesticides can alter how well the skin absorbs it (Brand and Mueller, 2002). Pesticides are put into mixtures to aid their absorption into plants. Sometimes these mixtures also make it easier for the skin to absorb the pesticide. Alachlor in pure form does not absorb into the skin as readily as when it is in a mixture. The United States Environmental Protection Agency (EPA, 1997) has averaged the amount of alachlor in a pesticide that can be absorbed by the skin during contact at 24% of the total concentration. Dermal absorption is one of the main routes of exposure for mixers and applicators of alachlor containing pesticides.

Inhalation Absorption

Little is known about the absorption rate of inhaled alachlor. Alachlor and other chemicals have the potential to enter the blood through the same pathways as oxygen. When alachlor is inhaled, it will enter the lung. It stands to reason that some will be exhaled, and some will be passed through the alveoli in the lungs to capillaries that carry blood away from the lungs and into the body. However, there is no evidence for toxicity or carcinogenic effects of inhaled alachlor, and there are no studies that explore how much alachlor can be absorbed into the blood through inhalation (WHO, 1996).

Ingestion Absorption

Ingestion has been the primary focus of most studies done on alachlor absorption. Alachlor is readily absorbed by the gastrointestinal (GI) system. Though very few human studies have been done, studies have been performed on rats, mice, dogs, and monkeys to determine how much alachlor is absorbed into the system and how it is distributed once it has entered the system. All of the alachlor that enters a system through ingestion is absorbed and either excreted or metabolized.

Distribution

Once alachlor is absorbed it is distributed to different areas of the body. If alachlor is absorbed through the skin, it is transported in the blood to the kidney. Once in the kidney, it is either filtered out or transported in urine to the bladder, or it remains in the blood. If alachlor is inhaled, it is likely that it absorbs into the blood that travels from the heart through lung tissue and back to the heart before being transported to the kidneys. Alachlor that is ingested may absorb into the stomach tissue or move into the intestines. Once in the intestinal tract, alachlor can then be absorbed into blood which flows through the liver. In the liver, alachlor can either be removed from the blood and transported to the kidneys for excretion or routed back into the general circulatory system. Alachlor can also be passed on from the small intestine to the large intestine and excreted in feces through the rectum.

Metabolism

Metabolism of alachlor occurs when the body chemically changes it to produce what are called metabolic products. The metabolic compounds or daughter products of alachlor can then be transported through the body in blood or excreted. There are many products of alachlor that can be formed through metabolism in animal systems. The metabolites of concern are those that can target certain tissues, cause cell damage, are detectable in urine/feces, and that catalyze the reactions of different metabolites that may cause toxicity. The major metabolites for alachlor that are of concern are:

  • DEA: diethylaniline
  • CDEPA: 2-chloro-N-(2,6-diethylphenyl) acetimide
  • HEEA: : 2-ethyl-6-(1-hydroxyethyl) aniline
  • ADEPS: 4-Amino-3,5-diethylphenyl sulfate

DEA is commonly used as a metabolite to determine human exposure because it can be found in urine (Driskell, et al, 1996). DEA can also metabolize into several other products that can be toxic in animal tissue (Logusch, et al, 1999). CDEPA has been found to bind to mouse liver DNA and calf thymus DNA making it a possible carcinogen (Nelson and Ross, 1997). HEEA has not been found in human urine/feces, but could be a potential toxic metabolite and has been detected in monkey urine (EPA,1997). ADEPS is not considered a toxic metabolite but is of interest because it is a metabolite that is formed from the same pathway as the metabolites of DEA that may be toxic (Logusch, et al, 1999). ADEPS could be used to predict possible toxic exposures as it can be found in the urine.

Metabolism of alachlor in rodents occurs in the cells of the liver, kidney, nasal turbinate, and stomach. Though metabolites can be found in human urine/feces the actual metabolic pathways in humans are little known (Driskell et al, 1996). Excretion routes vary in amounts found in the urine and feces depending upon the animal. However, tests done on the recovery of alachlor and its’ metabolites in excrement have shown that high percentages (approximately 70-95 %) of the administered dose are excreted from the system via these pathways.

References

Brand, Rhonda M. and Cynthia Mueller. 2002. Transdermal Penetration of Atrazine, Alachlor, and Trifluralin: Effect of Formulation. Toxicological Sciences. 68: 18-23.

Driskell, W.J., R.H. Hill Jr., D.B. Shealy, R.D. Hull, and C.J. Hines. 1996. Identification of a Major Human Urinary Metabolite of Alachlor by LC-MS/MS. Bulletin of Environmental Contamination and Toxicology. 56: 853-859.

Logusch, Sherry J., Paul C.C. Feng, Hideji Fujiwara, William C. Hutton, and Stephen J. Wratten. 1999. Enzymatic Synthesis of 4-Amino-3,5-diethylphenyl Sulfate, a Rodent Metabolite of Alachlor. Journal of Agriculture and Food Chemistry. 47:5:2125-2129.

EPA. Alachlor Reregistration Eligibility Decision, 1997

WHO. 1996. WHO/FAO Data Sheets on Pesticides, No. 86, Alachlor