Dinitrophenol

Dinitro Compounds are the organic compounds that contain 2 Nitrogen groups per molecule.

 Dinitro-ortho-cresol(DNOC), Dinitrophenol(DNP), Dinoseb,Dinoterb are the         commonly used dinitro compounds in agriculture as a​herbicide ​(control of broad leaf weeds in cereals and for the pre harvest desiccation of potatoes and leguminous seed crops) , larvicide , ovicide ​ ,dormant spray insecticide ​ ( against locusts and other insects). They are also used as an intermediate in the chemical industry.

Dinitro Compounds are slightly water soluble,hazardous to humans and animals as they have  narrow therapeutic windows ( that means they are toxic even while taking small doses) and  may cause developmental toxicity.

Sources :

Can be exposed by inhalation or dermal contact during manufacture or formulation of             pesticides

• From use in agricultural field
• From plastic industry
• May have been released to water in industrial effluents,by direct pesticidal application or by eaching or runoff.

Kinetics:

Well absorbed through the skin as well as by ingestion or inhalation of aerosols.Skin is the  principal route of exposure in agricultural workers.

• Metabolic pathway is identical in several non ruminant mammalian species,but the rate at which it is cleared from the organism varies between species.
• In ruminants first undergo an initial phase of bacterial metabolism in the rumen before it is absorbed in the blood.
• Distributed rapidly throughout the body
• Excreted in the urine
• Fatal dose→ 1 to 2 gms
• Fatal period→ 4 to 15 days

Mechanism of toxicity :

 DNP

• It is a p​rotonophore allowing protons(H​+​) to leak across the inner mitochondrial membrane   and thus bypass ATP synthetase. This makes ATP energy production less efficient.Ineffect,  part of the energy that is normally produced from cellular respiration is wasted as heat and  leads to extreme hyperthermia.The inefficiency is proportional to the dose of DNP that is taken. As the dose increases and energy production is made more inefficient, metabolic rate  increases (and more fat is burned) in order to compensate for the inefficiency and to meet  energy demands.
• DNP is probably the best known agent for uncoupling oxidative phosphorylation.​Uncoupling causes release of calcium from mitochondrial stores and prevents calcium reuptake,leads to free intracellular calcium and causes muscle contraction.

Signs and symptoms of toxicity     

 They are considered to have high acute toxicity.

❖ Increased basal metabolic rate

❖ Hyperthermia & Profuse diaphoresis

❖ Tachypnea & Pulmonary oedema

❖ Tachycardia & Arrhythmias

 ❖ Agitation , Dizziness , Anxiety , Tiredness , Insomnia

 ❖ Convulsion , Coma

❖ Nausea , Vomiting , Diarrhoea

 ❖ Yellow color of skin and hair , burns of lip and buccal mucosa

 ❖ Acute congestion of liver & Acute renal failure

Chronic exposure may lead to formation of Cataracts and Skin lesions and effects on bone marrow,CNS,CVS.

Diagnosis :

   High clinical suspicion is needed          

     1) History               

     2) Clinical signs               

      3) Lab                     

        →  Blood glucose        

        →  CBC(complete blood count)                    

         → Arterial blood gas / venous blood gas  Co-oximetry to evaluate for         methemoglobinemia                     

         →  Lactate              

       →  Coagulation studies                  

   →  Creatine phosphokinase                      

→  Urine analysis                  

   →  ECG                     

→  Chest X-ray                  

   →  CT brain and/or LP as needed

​Treatment    :

           ​  Symptomatic treatment

• Monitoring constant body temperature,cardiac monitor,IV access and code cart to bedside
• Activated charcoal if within 1 hr of ingestion, No evidence for or against multiple doses of charcoal or whole bowel irrigation
• Aggressive IVF(Intravenous fluid) administration (cooled if possible)
• Vasopressors with cardiovascular collapse if non responsive to IVF
• Treat methemoglobinemia as needed

   ​ For Hypothermia

 ​  : External cooling with blankets, ice and cooling devices                                  

    : cool IVF                                  

    : Control agitation(because it adds hyperthermia)

For agitation

: Benzodiazepines should be administered as needed , paralyze and intubate if not                controlled but maintain continuous & aggressive sedation.

  : Treatmentwithdantrolenewouldseemtoofferbenefitsince;dantroleneinhibitsrelease             of calcium from sarcoplasmic reticulum hence reduction in muscle contraction and heat generation.

Prognosis  

• Guarded to good with prompt diagnosis and treatment otherwise results in death
• Take weeks to recover

 Differential Diagnosis:

 PNA with respiratory failure  

Pericarditis                

 Pharyngitis                         

  Peritonitis                               

 Endocarditis 

 Acute adrenal insufficiency 

 Sickle cell disease          

Gout                             

 Pulmonary edema                                                        

 Crohn’s disease                             

 Heart stroke                              

Malignant Hyperthermia