Excretion herbicides

TCDD is the most potent inducer of chloracne. This has been well known since the accident in Seveso, Italy, in 1976 in which large amounts of TCDD were distributed in the environment subsequent to an explosion in a factory that produced a chlorophenoxy herbicide, 2,4,5-T. TCDD is an impurity produced during the production of 2,4,5-T. The most common long-term effect of TCDD exposure was chloracne. Exposed individuals also suffered increased excretion of porphyrins, hyper-pigmentation, central nervous system effects, and liver damage and increased risk of cancer was a long-term consequence of the exposure. In addition to TCDD, polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans, and polychloronaphthalens cause chloracne as well as other effects typical of TCDD. 7i... 

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). 

In crop protection as well, understanding plant metabolism is of paramount importance to increase selectivity and to address resistance of chemical compounds. Moreover, dissipation of a compound in the aquatic ecosystem is very similar to the excretion phenomena of the bodies. An extensive amount of evidence has been accumulated to support the involvement of CYPs in the metabolism and detoxification of herbicides, fungicides and insecticides. The understanding of their biotransformations at the molecular level may be extremely helpful for herbicide- or insecticide-synergistic development. 

The rapid degradation of molinate and conversion to more polar metabolites which are excreted into water serves to explain the extremely low bioaccumulation potential of this herbicide in fish. 

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. 

The following review summarizes the findings in all reported studies on excretion of 2,1+,5-T by humans given oral doses, or exposed to the herbicide under normal field conditions, including careless work habits. 

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.) ... 

Figure 1. Excretion of 2,4,5-T in two couples applying the herbicide with backpack sprayers (arrows indicate application dates). Key Couple 1 ---------, male (2) , female (3) Couple 2 ...

Figure 3. Excretion of 2,4,5-T in four men applying the herbicide with a tractor drawn mistblower...

T excreted by the 21 forest workers in two exposures under typical field conditions. The highest dose was received by mixers who handled the herbicide concentrate, followed by applicators using backpack sprayers, spray tractor drivers, helicopter... 

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. 

Broad spectrum Animals. Rapidly excreted by rat, goat, and herbicide controlling hen. Metabolism via cleavage of the molecule grasses followed by conjugation of flurophenyl... 

In general, most of the herbicides are only moderately to slightly toxic to fish, having median tolerance limits (Tim) generally above 1 p.p.m. A few, however, exhibit Tims well below 1 p.p.m. When fed to dairy and meat animals at dietary concentrations of several parts per million, the herbicides, in general, are not excreted in milk and do not accumulate in tissues. While this seems to be the case for the herbicide per se, the metabolites of many of the herbicides have not been fully investigated. 

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%... 

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