PRINCIPLES OF TOXICOLOGY - Biology East Borneo

356 PROPERTIES AND EFFECTS OF PESTICIDES15.4 HERBICIDESChlorophenoxy HerbicidesThe chlorophenoxy herbicides 2,4-dichlorophenoxy acetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) are probably the most commonly recognized of the chlorophenoxy herbicides.These compounds exert their action in plants by acting as growth hormones, but have no such hormonalaction in animals or humans. Some of the commonly used chlorophenoxy herbicides include Banvel(dicamba), Weedone (2,4-D), and Basagran M (MCPA) (see Figure 15.4).Acute Toxicity2,4-Dichlorophenoxyacetic acid (2,4-D) is prepared commercially by the reaction of 2,4-dichlorophenoland monochloroacetic acid. Other chlorophenoxy herbicide analogs include 2,4-DB, 2,4-DP,MCPA [(4-chloro-2-methylphenoxy) acetic acid], MCPP, and the herbicides 2,4,5-trichlorophenoxyaceticacid (2,4,5-T) and 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP; Silvex) thatare no longer used.Dioxin (2,3,7,8-TCDD) has not been identified in 2,4-D formulations (WHO, 1984). While in thepast, 2,3,7,8-TCDD contamination may have occurred in 2,4-D, this was due to contamination fromthe production of 2,4,5-T. The synthesis of 2,4-D does not produce 2,3,7,8-TCDD.The primary routes of exposure to chlorophenoxy herbicides are dermal and inhalation. Chlorophenoxycompounds act by uncoupling oxidative phosphorylation and decreasing oxygen consumptionin tissue. These compounds are fairly rapidly excreted and do not accumulate in the body. Thesecompounds are excreted via the urine primarily, and apart from conjugation of acids, little biotransformationoccurs in the body.Following ingestion, the acute toxicity of chlorophenoxy herbicides includes irritation of themucous membranes and gastrointestinal lining. Large intentional overdoses with chlorophenoxy acidshave resulted in symptoms of coma, metabolic acidosis, myotonia, mucous membrane irritation, andmyalgias. While cases of peripheral neuropathy following exposure to 2,4-D have been reportedsporadically throughout the literature, no causal association between this compound and neuropathyhas been proved.Treatment of cases of overexposure with chlorophenoxy herbicides is symptomatic and alsoinvolves decontamination.Carcinogenicity2,4-D is currently classified as a “D” carcinogen (not classifiable) by the USEPA. A recent mortalitystudy of chemical workers exposed to 2,4-D and its derivatives found no evidence of increasedmortality from cancer, including non-Hodgkin’s lymphoma. 2 A recent review of the available animaland human data for the chlorophenoxy herbicides 4-chloro-2-methyl phenoxyacetic acid (MCPA),2-(4-chloro-2 methylphenoxy) propionic acid (MCPP), and 2-(2,4-dichlorophenoxy) propionic acid(2,4-DP) concluded that there was no evidence to indicate that these compounds were carcinogenic tohumans.2 2,4-D has been classified as a group D carcinogen by the USEPA Office of Pesticide Programs. In their recentreview of 2,4-D (USEPA OPP, 1996) entitled “Carcinogenicity Peer Review (4th) of 2,4-DichlorophenoxyaceticAcid,” the Office of Pesticide Programs concluded: “The Health Effects Division Carcinogenicity Peer ReviewCommittee (CPRC) met on July 17, 1996 to discuss and evaluate the weight-of-the-evidence on 2,4,-D withparticulate reference to its carcinogenic potential. The CPRC concluded that 2,4-D should remain classified as aGroup D—Not Classifiable as to Human Carcinogenicity” and “The CPRC agree that 2,4-D should remainclassified as a Group D . . . . In two new adequate studies in rodents, which were conducted at doses high enoughto assess the carcinogenic potential of 2,4-D, there were no compound related statistically significant increases intumors in either rats or mice.”