Urine excretion herbicides

Sulfonylurea herbicides are generally applied to crops as an early post-emergent herbicide. Crops that are tolerant to these herbicides quickly metabolize them to innocuous compounds. At maturity, residues of the parent compound in food and feed commodities are nondetectable. Metabolites are not considered to be of concern, and their levels are usually nondetectable also. For this reason, the residue definition only includes the parent compound. Tolerances [or maximum residue limits (MRLs)] are based on the LOQ of the method submitted for enforcement purposes and usually range from 0.01 to 0.05 mg kg (ppm) for food items and up to O.lmgkg" for feed items. There is no practical need for residue methods for animal tissues or animal-derived products such as milk, meat, and eggs. Sulfonylurea herbicides are not found in animal feed items, as mentioned above. Furthermore, sulfonylurea herbicides intentionally dosed to rats and goats are mostly excreted in the urine and feces, and the traces that are absorbed are rapidly metabolized to nontoxic compounds. For this reason, no descriptions of methods for animal-derived matrices are given here. 

Diquat and paraquat are quaternary ammonium compounds largely used as contact herbicides and crop desiccants. When systemic absorption occurs, paraquat and diquat are rapidly distributed into the body. Paraquat primarily accumulates in the lungs and kidneys, while the highest diquat concentrations have been found in the gastrointestinal tract, liver, and kidneys (WHO, 1984). Urine is the principal route of excretion for both diquat and paraquat, which are primarily eliminated as unmodified compounds. Occupationally exposed workers can be monitored by measuring paraquat and diquat concentrations in urine samples (Table 6). Blood concentrations are useful to monitor acute poisoning cases. 

Atrazine, used as a selective pre- and post-emergence herbicide to control annual weeds in several crops, is the most representative compound of this group. It is also used as a non-selective herbicide in non-crop areas. After absorption, the compound is metabolized to dealkylated and deisopropy-lated derivatives. The unchanged compound and its metabolites are excreted in urine, where they can be detected by chromatography or enzyme-linked immunosorbent assay (Lucas et al., 1993). A mercapturic acid conjugate of atrazine has also been found in urine samples of workers spraying this herbicide (Lucas et al., 1993) (Table 6). 

The closely related herbicides have some differences in distribution and pharmacokinetics which are largely resolved by returning to the observation above that the water solubility of 2,4-D is about 3-fold greater than that of 2,4,5-T. Thus, 2,4-D has initial and final t., values as well as clearance value, about 3 times those founa for 2,4,5-T. These data all fit with the major distribution difference of these 2 compounds, i.e., that considerably more of the dose of 2,4-D is excreted in the urine in 24 hrs. 

D absorbed is excreted in the urine and because dermal exposure is considered the most likely exposure route ( 1, 2,3). Excretion studies on phenoxy herbicides in man (J3-6) show that 90% of the 2,4,5-T and 75% to 95% of the 2,4-D was excreted unchanged... 

Studies in animals and humans have shown that oral doses of phenoxy herbicides are rapidly absorbed and are excreted virtually completely as phenoxy acids in urine with a half-life of less than 1 day. 

Numerous studies on the metabolism of 2,1t-dichlorophenoxy-acetic acid (2,1+-D) and related herbicides in animals have shown that these chemicals are absorbed and distributed rapidly in the body, and are excreted, undegraded, relatively quantitatively in the urine within a week after administration (M Pharmacokinetic studies with 2,1+,5-T in rats and dogs (5.) and in humans (6J supported these findings, and demonstrated that rates of clearance from plasma and elimination in urine depend on dosage level, animal species, and chemical structure of the phenoxy acid being studied ( + ). Corresponding chlorinated phenol metabolites were detected only in ruminants (M or in trace amounts in urine of rats fed very high doses of phenoxy herbicides (7.) ... 

Our evaluations using 2,4,5-T and 2,4-D have been conducted over the past 5 years in forests in Arkansas, Oregon and Washington. Objectives were to measure external exposure and internal doseage as determined by the total amount of the herbicide excreted in the urine and also to develop the best possible techniques for assessing exposure and dose absorbed. Exposure levels were related to job responsibilities and to protective techniques designed to limit exposure. 

Although the toxic effects of 2,4,5-T may even be somewhat less than those of 2,4-D, observations of 2,4,5-T toxicity have been complicated by the presence of manufacturing by-product TCDD. Experimental animals dosed with 2,4,5-T have exhibited mild spasticity. Some fatal poisonings of sheep have been caused by 2,4,5-T herbicide. Autopsied carcasses revealed nephritis, hepatitis, and enteritis. Humans absorb 2,4,5-T rapidly and excrete it largely unchanged through the urine. 

Chlorophenoxy herbicides are readily absorbed through the gastrointestinal tract and distributed throughout the body. They are excreted unchanged mainly in the urine and are generally not stored in the body. Studies in laboratory rats given 1, 5, or 10 mg kg of " C 2,4-D have shown that 94-99%... 

The fates of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) 2, 4, 5-trichlorophenoxyacetic acid (2,4,5-T) and the DDT metabolite, bis-(4-chlorophenyl) acetic acid (DDA) were studied in the spiny lobster, Panulirus argus 24). All acids were injected intrapericardially at 10 mg/kg. Both 2,4-D or 2,4,5-T were extensively excreted, unchanged, in urine in the first 24 hours after the dose. About 10% of the dose of 2,4,D and 2,4,5T was taken up by hepatopancreas where the taurine conjugate was formed and subsequently excreted either in urine or feces. Part of the DDA dose was excreted in urine, as unchanged DDA and as DDA-taurine, but DDA was more extensively taken up by shell and hepatopancreas and more slowly excreted than 2,4D or 2,4,5-T. For all three carboxylic acids, muscle concentrations were lower than hemolymph concentrations at 24 hours after the dose, and were less than 5p.g/g. 

Mammals do not accumulate urea herbicides introduced orally. The dose administered is excreted within a few days in the urine and the feces, partly in unchanged form, partly in the form of metabolites. As in plants the main pathways of metabolism are demethylation, demethoxylation, ring hydroxylation and conjugation, although animals metabolise the compounds more rapidly. 

In order to facilitate data handling, several mini-computers were interconnected and the system directly connected to balances and apparatus for counting radioactivity. By use of Che occlusive method, an organic base and a ChiocarbamaCe insecticide were shown Co be absorbed and excreted readily. Very little material was retained in Che tissues of Che rats. By use of Che non-occlusive method, the insecticide, mechidathion, was shown Co be absorbed about 3 times faster Chan Che herbicide, aCrazine. Also, Che mouse absorbed the insecticide faster than Che rat. In the case of atrazine, use of four different treatment amounts showed a direct relationship between the amount placed on the skin and the amount found in the urine. This shows that urine analyses for atrazine residues would measure the amount of skin exposure. 

Hair is simple to collect and analyze, but arsenic levels in hair do not respond rapidly to exposure. Blood both is difficult to collect and does not give a consistent or rapid enough response to As exposure of an organism. Thus, even with the attendant collection problems, urine is the most practical index to the exposure of forest workers to the organic arsenical herbicides. Unfortunately, the pharmacokinetics of these herbicides have not been fully developed for dermal exposure, and there are indications that urine is not the sole excretory route. Thus, estimates of exposure based only on As excretion in urine may be only 30% of actual exposure levels (2 8). 

It Is realized that the pharmacokinetics governing absorption and excretion rates for many pesticides have not been fully evaluated. This fact should not automatically release the researcher conducting applicator exposure measurements from any obligations to attempt to gather Information regarding the absorbed dose. Since analysis of urine sometimes reveals the presence of a degradation product or the parent pesticide itself, as In the case of the phenoxy herbicides, a researcher is remiss If he does not at least attempt to locate a definable urinary component. 

If urine or blood samples are to be used to determine the absorbed dose, it is helpful to have pre-study information which will give the researcher an opportunity to design his sample collection scheme in a manner which will be simplest to achieve and which will provide the most quantitative information. Much has been written with regard to the excretion rates, quantitative nature of the excretion, and other data on the phenoxy herbicides. For other compounds where less is known, if the manufacturer can not provide detailed information on the excretion data, the researcher may be required to conduct a small controlled study, evaluating excretion rate, and other important characteristics of the compound prior to conducting full-scale field study. It is necessary to know if one should analyze for the parent compound or a metabolite. If a metabolite is to be analyzed, it is necessary to know if its amount can be related to the dose of the parent compound. 

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