PRINCIPLES OF TOXICOLOGY

356 PROPERTIES AND EFFECTS OF PESTICIDES
15.4 HERBICIDES
Chlorophenoxy Herbicides
The chlorophenoxy herbicides 2,4-dichlorophenoxy acetic acid (2,4-D) and 2,4,5-trichlorophenoxy
acetic 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 hormonal
action 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 Toxicity
2,4-Dichlorophenoxyacetic acid (2,4-D) is prepared commercially by the reaction of 2,4-dichlorophenol
and 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-trichlorophenoxyacetic
acid (2,4,5-T) and 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP; Silvex) that
are no longer used.
Dioxin (2,3,7,8-TCDD) has not been identified in 2,4-D formulations (WHO, 1984). While in the
past, 2,3,7,8-TCDD contamination may have occurred in 2,4-D, this was due to contamination from
the 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. Chlorophenoxy
compounds act by uncoupling oxidative phosphorylation and decreasing oxygen consumption
in tissue. These compounds are fairly rapidly excreted and do not accumulate in the body. These
compounds are excreted via the urine primarily, and apart from conjugation of acids, little biotransformation
occurs in the body.
Following ingestion, the acute toxicity of chlorophenoxy herbicides includes irritation of the
mucous membranes and gastrointestinal lining. Large intentional overdoses with chlorophenoxy acids
have resulted in symptoms of coma, metabolic acidosis, myotonia, mucous membrane irritation, and
myalgias. While cases of peripheral neuropathy following exposure to 2,4-D have been reported
sporadically throughout the literature, no causal association between this compound and neuropathy
has been proved.
Treatment of cases of overexposure with chlorophenoxy herbicides is symptomatic and also
involves decontamination.
Carcinogenicity
2,4-D is currently classified as a “D” carcinogen (not classifiable) by the USEPA. A recent mortality
study of chemical workers exposed to 2,4-D and its derivatives found no evidence of increased
mortality from cancer, including non-Hodgkin’s lymphoma. 2 A recent review of the available animal
and 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 to
humans.
2 2,4-D has been classified as a group D carcinogen by the USEPA Office of Pesticide Programs. In their recent
review of 2,4-D (USEPA OPP, 1996) entitled “Carcinogenicity Peer Review (4th) of 2,4-Dichlorophenoxyacetic
Acid,” the Office of Pesticide Programs concluded: “The Health Effects Division Carcinogenicity Peer Review
Committee (CPRC) met on July 17, 1996 to discuss and evaluate the weight-of-the-evidence on 2,4,-D with
particulate reference to its carcinogenic potential. The CPRC concluded that 2,4-D should remain classified as a
Group D—Not Classifiable as to Human Carcinogenicity” and “The CPRC agree that 2,4-D should remain
classified as a Group D . . . . In two new adequate studies in rodents, which were conducted at doses high enough
to assess the carcinogenic potential of 2,4-D, there were no compound related statistically significant increases in
tumors in either rats or mice.”