The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral administration to man

Sauerhoff, Mitchell W.; Braun, Werner; Blau, Gary; Gehring, P.J.

doi:10.1016/0300-483x(77)90018-x

Cited by 153 publications

(80 citation statements)

References 3 publications

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“…Following an oral, dermal or inhalation exposure to 2,4-D ( dimethylamine salt ), close to 100% of the absorbed dose is excreted in the urine as 2,4-D acid over a 5 -to 6 -day period (Feldman and Maibach, 1974;Kohli et al, 1974;Sauerhoff et al, 1977;Harris and Solomon, 1992b). Following repeated exposures, a steady state for 2,4-D body burden would be reached following approximately four half -lives or 4-5 days of consecutive exposure, if the exposure to 2,4-D, on a daily basis, remains relatively constant.…”

Section: Dose Estimationmentioning

confidence: 99%

Development of models to predict dose of pesticides in professional turf applicators

Harris

Sass-Kortsāk

Corey

et al. 2002

J Expo Sci Environ Epidemiol

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Epidemiologic studies designed to assess the chronic effects of pesticides are limited by inadequate measurements of exposures. Although cohort studies have been initiated to evaluate the effects of 2,4 -dichlorophenoxyacetic acid ( 2,4 -D ) and other pesticides in professional turf applicators, they may have limited power to detect significant health risks and may be subject to bias from exposure measurement error. In this study, the doses of 2,4 -D, mecoprop [ 2 -( 4 -chloro -2 methylphenoxy ) propionic acid, MCPP ] and dicamba ( 3,6 -dichloro -o -anisic acid ) were evaluated in a group of 98 professional turf applicators from 20 companies across southwestern Ontario. During a 1 -week period ( Saturday to Thursday ), the volume of pesticide ( active ingredient ) applied was only weakly related to the total dose of 2,4 -D absorbed ( R 2 = 0.21 ). Two additional factors explained a large proportion of variation in dose: the type of spray nozzle used and the use of gloves while spraying. Individuals who used a fan -type nozzle had significantly higher doses than those who used a gun -type nozzle. Glove use was associated with significantly lower doses. Job satisfaction and current smoking influenced the dose but were not highly predictive. In the final multiple regression models predicting total absorbed dose of 2,4 -D and mecoprop, approximately 63 -68% of the variation was explained. The future application of these models for epidemiologic research will depend on the availability of information and records from employers, the feasibility of contacting study subjects and cost.

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Section: Dose Estimationmentioning

confidence: 99%

Development of models to predict dose of pesticides in professional turf applicators

Harris

Sass-Kortsāk

Corey

et al. 2002

J Expo Sci Environ Epidemiol

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“…This should be checked, although present lack of understanding of the role of this enzyme system makes toxicological assessment impossible. Along these lines, it has been shown that these chlorophenoxy acids do not accumulate in human tissue after single dose ingestion, although short term plasma levels in human subjects of over 0.1 mm have been reported (2,4 …”

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confidence: 99%

2,4-Dichlorophenoxyacetic Acid Inhibits the Outer Membrane NADH Dehydrogenase of Plant Mitochondria

Mannella¹,

Bonner²

1978

Plant Physiol.

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The NADH dehydrogenase of potato (Solanum tuberosum) and mung bean (Phaseolus aureus) outer mitochondrial membranes is specifically inhibited by both 2,4-dchlorophenoxyacetic and 2,4,5-trichlorophenoxyacetic acids but not by the natural auxin indole-3-acetic acid.The chemical agent 2,4-D is widely used as a selective herbicide although its biochemical mode of action is not fully understood. We have found that 2,4-D inhibits the NADH dehydrogenase system associated with the outer membranes of potato (Solanum tuberosum) and mung bean (Phaseolus aureus) mitochondria. [ Inhibition by 2,4-D is detectable only at initial NADH levels below this value (Fig. 2), indicating that 2,4-D acts at the dehydrogenase. The mode of inhibition of the NADH dehydrogenase by 2,4-D is complex, appearing competitive with NADH at concentrations of this substrate just below 0.2 mm and uncompetitive at very low NADH concentrations (Fig. 2 and ref. 3). At an initial NADH level of 0.1 mm, concentrations of 2,4-D approaching its water solubility limit (about 2 mM) produce essentially complete inhibition of this outer mitochondrial membrane activity, while inhibiting the microsomal NADH-Cyt c oxidoreductase to a far lesser extent (Fig. 1). It was found that the related compound 2,4,5-trichlorophenoxyacetic acid is also a specific inhibitor of the outer mitochondrial membrane NADH dehydrogenase while IAA, the natural auxin whose hormonal action appears to be mimicked by these chlorophenoxy acids, is not.Since the function of the NADH dehydrogenase-Cyt bs,% system of the outer mitochondrial membrane is not known, the physiological relevance of its inhibition by these compounds is unclear. A possibility suggested by these results is that this electron transfer system is involved, in plants, in

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“…In the environment, it has a half-life of 2-14 days (Starrett, et al, 2000), and it can persist in agricultural soils for longer periods. It can be absorbed by the human body after long periods of contact, but it is cleared quickly via urine without being metabolized or accumulating in tissues (Sauerhoff et al, 1977). Despite this, 2,4-D has been linked to human genotoxicity (Charles et al, 2001), carcinogenesis (Glickman et al, 2004), neurotoxicity (Bongiovanni et al, 2007), and reproductive toxicity (Arbuckle et al, 1999a).…”

Section: Introductionmentioning

confidence: 99%

Toxic effects of 2,4-dichlorophenoxyacetic acid on human sperm function <i>in vitro </i>

et al. 2016

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-The herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) is globally used in agriculture and has been linked to human sperm abnormalities in vivo. However, its effects on ejaculated human spermatozoa in vitro have not been characterized. Therefore, we examined the effects of 2,4-D on the functions of ejaculated human spermatozoa in vitro, including: sperm motility, the ability to move through a viscous medium, capacitation, and the acrosome reaction. Different doses of 2,4-D (10 nM, 100 nM, 1 μM, 10 μM, 100 μM, and 200 μM) were applied to human spermatozoa prepared from normal fresh semen samples. The results indicated that 2,4-D did not affect the viability, capacitation, or spontaneous acrosome reactions of human spermatozoa, but it dose-dependently inhibited the total motility, progressive motility, ability to penetrate viscous medium, and progesterone-induced capacitation and acrosome reaction rates. These results suggest that exposure to 2,4-D and its accumulation in the seminal plasma and follicular fluid might increase the risk of infertility. Our findings provide new insights for understanding the male reproductive toxicity of 2,4-D.

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The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral administration to man

Cited by 153 publications

References 3 publications

Development of models to predict dose of pesticides in professional turf applicators

Development of models to predict dose of pesticides in professional turf applicators

2,4-Dichlorophenoxyacetic Acid Inhibits the Outer Membrane NADH Dehydrogenase of Plant Mitochondria

Toxic effects of 2,4-dichlorophenoxyacetic acid on human sperm function <i>in vitro </i>

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