Phenoxy herbicides, toxicity

Conversion of a nontoxic molecule to one that is toxic, or a molecule with low potency to one that is more potent. Examples include the formation of the phenoxy herbicide 2,4-D from the corresponding butyrate, formation of nitrosamines, and methylation of arsenicals to trimethylarsine. 

In contrast to the broad-spectrum herbicides, others are more selective. The phenoxy herbicides, which include chemicals such as 2,4-D, 2,4,5-T, and MCPA, are toxic to broad-leaf plants but do not affect narrow-leaf plants such as grasses. 

The phenoxy herbicides inexpensiveness, selectivity, nonpersistency and low toxicity to animals are difficult to beat. Application is usually accomplished by spraying on the leaves. The herbicides cannot themselves be applied to the soil because they are washed away or decomposed by microorganisms in a few weeks. They can be applied by this method using a sulfonic acid derivative that, after hydrolysis in the soil and oxidation by bacteria, can form 2,4-D in the plant. 2,4-D is still the main herbicide used on wheat. 

The presence of TCDD in 2,4,5-T is believed to be largely responsible for other human toxicities associated with the herbicide. There is epidemiologic evidence indicating an association between occupational exposure to the phenoxy herbicides and an excess incidence of non-Flodgkin s lymphoma. The TCDD contaminant in these herbicides seems to play a role in a number of cancers such as soft tissue sarcomas, lung cancer, Flodgkin s lymphomas, and others. 

Polychlorinated Dibenzo-(p)-Dioxins and Dibenzo-Furans. Another group of compounds that we need to specifically address are the polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo-furans (PCDFs) (Fig. 2.15). The PCDDs and PCDFs are not intentionally produced but are released into the environment from various combustion processes and as a result of their occurrence as unwanted byproducts in various chlorinated chemical formulations (e.g., chlorinated phenols, chlorinated phenoxy herbicides see Alcock and Jones, 1996). Because some of the PCDD and PCDF congeners are very toxic (e.g., 2,3,7,8-tetrachloro dibenzo-p-dioxin, see margin), there have been and still are considerable efforts to assess their sources, distribution, and fate in the environment. Similarly to the PCBs or DDT (see above), the PCDDs and PCDFs are highly hydrophobic and very persistent in the environment. It is therefore not surprising that they have also been detected everywhere on earth (Brzuzy and Hites, 1996 Lohmann and Jones, 1998 Vallack et al., 1998). Finally, we should note that polybrominated diphenylethers (PBDEs, see margin) that, like the PBBs (see above), are used as flame retardants, are of increasing environmental concern (de Boer et al., 2000). 

The extent to which exposure to pesticides may be hazardous to applicators depends upon exposure levels and the toxicity of the compounds. The phenoxy herbicides have been used for nearly 40 years, and no injury to workers properly using these herbicides has been clearly established. 

In spite of their record of producing no detectable harm to humans, the phenoxy herbicides 2,4-dichlorophenoxy acetic acid (2,4-D) and 2,4,5-trichlorophenoxy acetic acid (2,4,5-T) have acquired a less than desirable reputation. This reputation has been the result of their association with low levels of impurities. They have commonly been used as a mixture, which contains trace amounts of highly toxic 2,3,7,8-tetrachlorodibenzo-jj-dioxin, a minor product in the manufacturing of 2,4,5-T. In early production of 2,4,5-T a low level of dioxin was retained. Today s manufacturing process produces 2,4,5-T with no more than 0.1 ppm of the 2,3,7,8 tetrachlorodibenzo-]D-dioxin. This association with toxic dioxin and confusion of the public and the media regarding these issues have led to public distrust in the safety of using phenoxys and to the need to establish clearly the extent of human exposure to these compounds as well as the resulting effects of this exposure. 

Including this extraneous exposure, the degree of safety that we calculated for forest workers using phenoxy herbicides was such that even the most highly exposed crewmembers received exposure which was several orders of magnitude below the noobservable-effect-level. Decreases in the level of exposure with the use of protective measures, however, may be of real consequence to workers applying more toxic materials. 

A brief summary of the toxicity of the forest herbicide 2,4-D can be presented as follows. Table IV shows the acute LD-50 values of most of the phenoxy herbicices. These range from 300 mg/kg for 2,4,5-T and 375 mg/kg for 2,4-D up to 6400 mg/kg for Bifenox. It is useful to set the acute oral toxicity for 2,4-D in the context of other phenoxy herbicides and in relation to other pesticides so the public can gain a perception of where 2,4-D fits on a scale of relative values with regard to... 

However, controlled or specific environmental degradation sometimes is necessary for herbicidal action. For example, the phenoxy herbicide sesone (sodium 2,4-dichlorophenoxyethyl sulfate) has no effect on plants until it can be oxidized to 2,4-D by a specific soil microorganism, Bacillus cereus (38). The growth regulator ethophon (Ethrel) relies upon slow environmental conversion into ethylene for its activity (39). And metham (Vapam) depends upon hydrolysis in soil to release toxic methyl isothiocyanate (40). 

Certain phenoxy herbicides adversely affect sensitive crops (7) such as cotton, grapes, and tomatoes at distances of as much as 15 miles from the site of application. With this type of herbicide, not only are the physical state, particle size, and extent of the area treated important, but also the vapor phase of the toxicant. Highly volatile herbicides have been known to adversely affect sensitive crops some distance away for a duration of several weeks. 

TCDD, the most toxic of the 75 dioxin isomers and possibly the most toxic manufactured chemical, contaminates phenoxy herbicides during the production process (Demers and Perrin 1995 Klaassen 1985). Conflicting literature addresses TCDD lethality in humans. Some reviews deny that human deaths result from systemic effects of TCDD (Demers and Perrin 1995). Others describe successful suicides with phenoxy herbicides (Nielsen et al. 1965). Despite extensive reports of numerous medical conditions from TCDD, the literature confirms only chloracne and transient mild hepatotoxicity in humans. Table 1-6 lists the various, but unconfirmed, signs and symptoms associated with human poisonings. Table 1-7 lists the unconfirmed psychiatric symptoms attributed to TCDD exposure. 

On the basis of long experiences and an immense amount of investigative material, phenoxy herbicides have been judged to be medium acute toxic and nonpersistent, and it has been determined that they do not accumulate in the organism. They are relatively toxic to fish and to organisms that serve as food for fish, while their normal use does not involve hazards for wildlife (Rowe and Hymas, 1954 Erne, 1975). They are generally hazardous to bees, so that their use is not permitted on flowering weeds. 

ACGIH. 1986. Documentation of Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH American Conference of Governmental Industrial Hygienists. Alexander, H. C., F. M. Gersich, and M. A. Mayes. 1985. Acute toxicity of four phenoxy herbicides to aquatic organisms. Bull. Environ. Contam. Toxicol. 35(3) 314-21. 

HUMANS EXPOSED TO MATERIALS REPORTED TO BE CONTAMINATED WITH TCDD HAVE DEVELOPED CHLORACNE AND OTHER SIGNS OF SYSTEMIC POISONING. SOFT TISSUE SARCOMA HAS BEEN OBSERVED IN EXCESS AMONG WORKERS EXPOSED TO PHENOXY HERBICIDES. THESE DATA ARE INCONCLUSIVE REGARDING TCDD TOXICITY IN HUMANS BECAUSE THE POPULATIONS STUDIED HAD MIXED EXPOSURES MAKING CAUSAL RELATIONSHIPS BETWEEN EXPOSURE AND EFFECT UNCLEAR. THE DATA ARE, HOWEVER, SUGGESTIVE OF AN ASSOCIATION BETWEEN EXPOSURE TO PHENOXYACETIC HERBICIDES CONTAMINATED WITH TCDD AND EXCESS LYMPHOMA AND STOMACH CANCER. ATTEMPTS TO ASSOCIATE REPRODUCTIVE EFFECTS WITH TCDD EXPOSURE ARE INCONCLUSIVE BECAUSE OF THE INADEQUATELY DEFINED POPULATIONS STUDIED AND THE DIFFICULTIES OF DEFINING EXPOSURE. 

Myotonia occurs when normal muscle contraction is not followed by full relaxation. Toxic dosages of the phenoxy herbicide 2,4-D causes myotonia in dogs. 

In addition to their own toxic properties, phenoxy herbicides can potentiate the toxic effects of some plants ... 

Since the same effects occurred with the non-herbicidal (2,6-dichloro-phenoxy) acetic acid as with toxic compounds, glucose metabolic changes are not the important singular effects of auxin herbicides. 

The acute toxicity of phenoxy-acid herbicides to humans and aquatic organisms is relatively low [87]. The USEPA maximum residue level for 2,4-D in drinking water is 70 000 ng/L, and the National Academy of Sciences has recommended a maximum concentration in water for protection of aquatic life of 3000 ng/L [78]. No Canadian guidelines for the protection of aquatic life and drinking water were exceeded (Table 8). 

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