Phenoxy-derivatives of fatty acids:

Sources :

• Are phenoxy acids/phenoxies.
• This family of chemicals is mostly related with herbicides.
• Some examples are: MCPA ( 2-methyl-4-chlorophenoxy acetic acid)                                   2,4-D   ( Dicholorophenoxy acetic acid ) 

 2,4,5-T ( Trichlorophenoxy acetic acid )     

• use was widespread in 1950s
• was later found that these were contaminated with a toxic agent TCDD(2,3,7,8-tetracholodibenzo-p-dioxin) and was banned in most countries as it was thought to cause diseases like Soft tissue sarcoma , NHS ,etc which was later not backed up so are still used in developing countries.
• Are used mostly as IAA (indole acetic acid) or growth hormones which are sprayed in the lawns and pastures causing uncontrolled growth in broad leaf plants and the plant “growing to death”.
• These herbicides are also known to increase the palatability of the plants leading to increased consumption hence causing toxicity in cattle.  Mostly cattle and dogs are more susceptible .
• Animals can tolerate repeated oral doses suggesting there is very little cumulative effects .
• Must be ingested in high doses in order to cause toxicity.

  Major sources are:-  

  Concentrated sprays

 freshly sprayed pastures and lawns (especially in monocot crop farms as they rarely affect them and kill the broad leafed weeds potently)

Mode of transmission:

 Major modes of transmissions are :-

• Accidental ingestion of concentrated sprays ( cattle ).
• Grazing in freshly sprayed pasture ( cattle )
• Access to freshly sprayed lawns ( dogs )

Mechanism of action:

It can act in the body through 3 ways :-

 INHALATION/INGESTION THROUGH DIFFERENT MODES WHICH LEADS TO

• DOSE DEPENDENT CELL MEMBRANE DAMAGE
• UNCOUPLING OF OXIDATIVE PHOSPHORYLATION CAUSING HAULT IN ATP FORMATION.
• DISRUPTION OF ACETYLCOA METABOLISM LEADING TO INCREASED KETONE BODIES AND CHOLESTROL LEVELS

Kinetics:

• Absorption occurs mainly through GI mucosa or by inhalation and rarely in a small amount through skin .
• Distributed all over the body including liver, kidney and brain .
• Metabolism occurs mainly through hydrolysis usually metabolized in a few hours (short) but takes up to 3-4 days(longer) in dogs.
• Excretion mainly through urine by tubular secretion in unchanged form. 

Clinical signs:

• GI system:- Vomiting , diarrhea and salivation(dogs) & abdominal pain, occasionally GI hemorrhage , rumen atony, bloat diarrhea (cattle) .
• Neurotoxin effects: – Hypertonia, hallucinations, sometimes with myopathic effects like limb muscle weakness and clonic spasms (dogs) & depression and muscular weakness (cattle) also muscle tremors. loss of tendon reflexes, seizures are also seen.
• Ophthalmic:- Irritation , conjunctivitis 
• Renal:- Azotemia , Tubular degeneration
• In rare cases respiratory failures

Diagnosis:

• History, clinical signs
• Lab:- 

 CBC(complete blood count)

  Serum Chemistry (elevated levels of ALP , LDH and CK )

  Serum/Tissue Assay( 100-700 ppm => recent exposure to toxic dose )

• Electromyographic

Treatment:

• For dermal exposures :- Bathe in warm water and use mild soap ( with PPE used)
• Ocular exposures :- Flush eyes with isotonic saline water for 10/15 minutes
• Larger oral exposure:-  Induce emesis ( less than 2 hours of exposure)

 Charcoal => 1/2gm/kg body wt ( < 2 hours of ingestion)

 Alkaline diuresis and Hemodialysis to increase elimination can also be considered

Differential diagnosis:

• GI irritants/toxins
• Primary GI diseases
• Metabolic diseases
• Nicotine/caffeine ingestion
• Primary neuropathy