Distribution of 2-methyl-4-chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male rats: Evidence for the involvement of the central nervous system in their toxicity

Elo, Heikki A.; Ylitalo, Pauli

doi:10.1016/0041-008x(79)90368-5

Cited by 46 publications

(15 citation statements)

References 20 publications

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“…It has now been observed that dimethylamine 2,4-D did not change the striatal levels of DA and HVA, a fact already described elsewhere (Elo & MacDonald 1989). On the contrary, we found a negative correlation (Pearson's correlation coefficient r = -0.84) between the decrease in rat locomotion frequency induced by the pesticide and the brain stem levels of 5-HIAA observed 3 hr after use.…”

Section: Discussionsupporting

confidence: 76%

“…The present data show a negative correlation (Pearson's correlation coefficient r = -0.79) between the 2.4-D effects on rat locomotor activity and its brain levels measured 3 hr after acute intoxication. According to Elo & Ylitalo (1979) signs of CNS depressive states in animals severely poisoned by 2,4-D were a consequence of a partial breakdown of the blood-brain barrier with subsequent accumulation of the herbicide within the brain. In accordance with Mattson et al (1986) only higher 2,4-D doses (greater than 150 mg/ kg) were able to induce lesions in the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

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Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on open-field behaviour and neurochemical parameters of rats

Oliveira

Palermo-Neto

1994

Toxicology Letters

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on open-field behaviour and neurochemical parameters of rats

Oliveira

Palermo-Neto

1994

Toxicology Letters

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“…Elo and Ylitalo [141] intravenously administered doses ranging from 10 to 250 mg/kg 14 C MCPA and 14 C 2,4-D to young and adult male Sprague-Dawley rats and determined the plasma and tissue distribution of these constituents at various times following administration. Highest concentrations were achieved approximately four hours following administration and declined thereafter with nearly complete elimination at 120 hours.…”

Section: Absorption Distribution Metabolism and Elimination (Adme)mentioning

confidence: 99%

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Stackelberg

2013

Journal of Toxicology

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Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin's disease (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

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“…In accordance with our data, the extent of binding of other chlorophenoxyacetic acid derivatives reaches 70 and 90%. [19][20][21]22 This binding of MCPA to plasma albumin excluded a distinct involvement of glomerular filtration ia renal excretion of MCPA. We have not measured whether or not bound MCPA can be filtered glomerularly together with albumin.…”

Section: Resultsmentioning

confidence: 99%

Renal handling of 2‐methyl‐4‐chlorophenoxyacetic acid (MCPA) in rats

Bräunlich

Bernhardt

1989

J of Applied Toxicology

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Following i.p. administration of various doses of 2-methyl-4-chlorophenoxyacetic acid (MCPA), ca. 50% is excreted during a 5-h diuresis experiment. After i.p. administration of MCPA, virtually no distribution occurs (Vrel = 18% of the body weight). Renal excretion of MCPA can be accelerated by inhibition of its renal tubular reabsorption. The distinct inhibition of renal excretion of MCPA by simultaneous administration of probenecid or p-aminohippurate (PAH) indicates the active tubular transport of MCPA; this transport process can be stimulated by treatment of rats with triiodothyronine. Active tubular transport of MCPA was confirmed by measurement of MCPA accumulation in renal cortical slices, both under aerobic and anaerobic conditions. Accumulation of MCPA under anaerobic conditions indicates an additional passive uptake and binding of MCPA in kidney tissue in accordance with the high degree of binding to plasma albumin (85%).

show abstract

Distribution of 2-methyl-4-chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male rats: Evidence for the involvement of the central nervous system in their toxicity

Cited by 46 publications

References 20 publications

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on open-field behaviour and neurochemical parameters of rats

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on open-field behaviour and neurochemical parameters of rats

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Renal handling of 2‐methyl‐4‐chlorophenoxyacetic acid (MCPA) in rats

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