Lapis ISSN 2398-2969

Toxicity: herbicide

Contributor(s): Lesa Thompson, Livia Benato

Introduction

  • Herbicides include many chemical classes, with difference mechanisms of action in plants, and a range of toxic effects in animals that are often species-specific.
  • Cause: in some cases, toxicity is via contact, whilst in others the chemical is translocated via soil or plant foliage. For some, toxicity may be due to additive ingredients, such as surfactants and emulsifiers, in the herbicide formulation. Toxic events in animals are usually a result of improper use or careless disposal of containers. Runoff from agricultural applications into drinking water may also occur.
  • Signs: newer herbicides generally have lower toxicity to mammals, though sub-clinical signs may include reproductive or developmental effects.
  • Diagnosis: history of possible exposure. Clinical signs depend on chemical.
  • Treatment: often palliative and of support.
  • Prognosis: depends on the particular herbicide, exposure dose and period.

Pathogenesis

Etiology

  • Depends on chemical in question.
  • Due to generally rapid excretion and little tissue retention, little cumulative effect seen with repeated doses, eg phenoxy herbicides.
  • Phenoxy acid derivatives:
    • 2,4-D is rapidly absorbed from the gastrointestinal tract in mammals.
    • Dermal absorption also possible.
    • Rapid distribution to liver, kidneys, lung and brain.
    • Excretion predominantly via urine.
  • Bipyridyl derivatives:
    • Paraquat rapidly absorbed from the gastrointestinal tract.
    • Mostly excreted in urine and feces unchanged.
    • It is also excreted unchanged in the bile. 60-70% of ingested paraquat is excreted in feces.
    • In the case of diquat, 90-98% is eliminated in urine, including some unidentified metabolites.
  • Organophosphorus herbicides:
    • Poor oral or dermal absorption.
    • Rapid elimination, not biotransformed, and don’t accumulate in tissues.
    • Glyphosate excreted rapidly, with >70% via feces and 20% via urine.
  • Oxidase inhibitor herbicides:
    • Either not readily absorbed, or rapidly degraded and/or excreted.
    • Metabolic degradation by various methods, with most metabolites excreted via urine, and small amounts in feces/milk.
  • Substituted anilines:
    • Metabolism and excretion vary greatly by species.
  • Dinitrophenol compounds:
    • In humans, it is absorbed by ingestion and by the skin.
    • Dinitro-o-cresol (DNOC) is highly hazardous.
    • Rabbits absorb  DNOC more easily than 2,4 dinitrophenol.
  • Polycyclic alkanoic acids:
    • More toxic with dermal exposure.
    • LD50 of diclofop is 180 mg/kg in rabbits.

Predisposing factors

General

  • Exposure susceptibility varies with access to herbicides:
    • Increased risk with poor storage of herbicides or their containers.
    • Outdoor pets with free access to garden areas where herbicides may have been used are at increased risk of exposure.
  • High doses will increase likelihood of clinical signs developing.
  • Most newly developed chemicals have low toxicity to mammals compared to older compounds.

Specific

  • Knowledge of herbicide use in the rabbit’s environment that permits exposure, either by contact or ingestion.

Pathophysiology

  • Mechanism of action of many herbicides is unknown.
  • Paraquat selectively taken up by lungs → pneumocytosis:
    • Redox cycling, lipid peroxidation → cell death.
  • Diquat’s major target organs are gastrointestinal tract, liver and kidneys:
    • Redox recycling (alternate reduction followed by reoxidation).
    • Diquat is not teratogenic and does not affect fertility.

Timecourse

  • Many herbicides have rapid elimination, often without metabolism, however this is both chemical and species-specific.
  • For example, the plasma half-life of 2,4-D is 3.5-18 h after oral exposure.
  • Paraquat shows increased serum levels within an hour from ingestion.
  • With paraquat toxicity, the major cause of death is lung damage which occurs after 2-7 days.
  • Ocular irritation from glyphosate usually disappears <48 h after exposure.

Epidemiology

  • Animals with similar exposure opportunities in their environment may succumb to similar toxic effects.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Gress S, Lemoine S, Puddu P E, Séralini G E & Rouet R (2015) Cardiotoxic Electrophysiological Effects of the Herbicide Roundup(®) in Rat and Rabbit Ventricular Myocardium In Vitro. Cardiovasc Toxicol 15 (4), 324-335 PubMed.
  • Gress S, Lemoine S, Séralini G E & Puddu P E (2015) Glyphosate-based herbicides potently affect cardiovascular system in mammals: review of the literature. Cardiovasc Toxicol 15 (2), 117-126 PubMed.
  • Idid S Z & Lee C Y (1996) Effects of Fuller’s earth and activated charcoal on oral absorption of parquat in rabbits. Clin Exper Pharmacol Physiol 23 (8), 679-681 PubMed.
  • Lee J et al (2015) Developmental toxicity assessment of the new turf herbicide, methiozolin ([5-(2, 6-difluorobenzyl) oxymethyl-5-methyl-3, 3 (3-methylthiophen-2-yl)-1, 2-isoxazoline]), in rabbits. Reg Toxicol Pharmacol 72 (3), 639-645 PubMed.
  • Moody R P, Franklin C A Ritter L & Maibach H I (1990) Dermal absorption of the phenoxy herbicides 2,4-D, 2,4-D amine, 2,4-D isooctyl, and 2,4,5-T in rabbits, rats, rhesus monkeys, and humans: a cross-species comparison. J Toxicol Environ Health 29 (3), 237-245 PubMed.
  • Murphy L A (2015) Environmental toxicology:  considerations for exotic pets. J Exotic Pet Med 24 (4), 390-397 VetMedResource.
  • Sandberg J A, Duhart H M et al (1996) Distribution of 2 4 dichlorophenoxyacetic acid in maternal and fetal rabbits. J Toxicol Environ Health 49 (5), 497-510 PubMed.
  • Zhi S et al (2015) Hemoperfusion alleviated paraquat-induced kidney inflammation injury of rabbit. [Article in Chinese] Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi [Chinese J Ind Hygiene Occupational Dis33 (9), 658-662 PubMed.

Other sources of information

  • Keeble E, Meredith A & Richardson J (2016) Eds Rabbit Medicine and Surgery: Self-Assessment Color Review. CRC Press, USA.
  • Gupta R C (2012) Ed Veterinary Toxicology: Basic and Clinical Principles. Academic Press Inc, USA.
  • Hayes W J Jr & Laws E R Jr (1991) Eds Handbook of Pesticide Toxicology. Vol 3: Classes of Pesticides. Academic Press Inc, USA.


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