Acute Renal Failure following Penoxsulam poisoning

To the Editor:

Penoxsulam is a fluorinated benzenesulfonamide. It is a herbicide used in dry and wet seeded crops mainly in rice paddies in Sri Lanka. Toxicity following human ingestion has not been reported before. Eye contact with penoxsulam dust or granules may cause slight irritation, although corneal injury is unlikely. Harmful effects are not anticipated from swallowing small amounts.¹ In animal studies, the predominant target organ were the kidney and the urothelium. Due to limited solubility in urine, penoxsulam forms crystals/calculi in the pelvis of the kidney and the lumen of the urinary bladder. Raised blood urea, reduced urine osmolality and increased urine volume were noted as secondary effects. Renal tubular degeneration was also sometimes observed. A treatment-related chronic progressive glomerulonephropathy was observed in male rats. Kidney damage seen in shorter-term studies was generally not exacerbated in longer-term studies.²

Human intoxication with Penoxsulam has not been reported before. We wish to report a patient who developed acute renal failure requiring dialysis. It is important to be aware of the possible renal toxicity of this herbicide.

A 25-year-old man was admitted 30 minutes after ingestion of ‘one mouth full’ of GRANITE® (penoxsulam240 g/L) concentrate. He complained of nausea, vomiting and faintness. His vital signs were stable. Blood pressure was 140/80 mmHg. Gastric decontamination was done via a nasogastric tube and activated charcoal was given. Routine investigations showed: haemoglobin 16.8 g/dL, white cells /10 700 mm³ urea 2.5 mmol/L, serum creatinine was 88 mmol/L, serum sodium 140 mmol/L and potassium 4.3 mmol/L. Urine output was normal. He was observed for 48 hours and discharged home. Seventy two hours later he presented with severe backache and loss of appetite. He was afebrile. Normal saline was given in order to avoid dehydration, and his urine output remained normal. His creatinine was 1135 mmol/L and urea was 22.6 mmol/L. Serum transaminases, bilirubin, calcium, phosphate and amylase were within normal limits. Urine analysis did not show any active sediment. Urine culture was sterile. Ultrasonic appearance of kidneys confirmed acute renal parenchymal disease. He was commenced on haemodialysis via a femoral catheter. He underwent six cycles of dialysis over period of 14 days. His creatinine gradually dropped to 184.8 mmol/L and was discharged home. One week after his creatinine was 79.2 mmol/L. Urine analysis remained normal. The patient did not have calculi in the follow-up imaging.

Considering the chronology of events and the renal toxicity in animal studies, it is reasonably safe to assume that acute renal failure in the index case is a direct effect of penoxsulam toxicity. However, the development of acute renal failure after a single oral ingestion of penoxsulam is unusual. In toxicity studies, renal injury was seen in subchronic (13 weeks) and chronic exposure (I year).³ Whereas a single dose produced no treatment related effects at the highest dose tested (1000 mg/kg/day).³ In this 40 kg man. a single ‘mouthful’ (25 ml of 240 g/L) would equate roughly to 150 mg/kg of active ingredient. Given that penoxsulam has very low oral toxicity (LD50 > 5000 mg/kg), it is surprising that this single oral dose (150 mg/kg) resulted in acute renal failure. The patient did not have a pre-existing renal disease. However, he comes from a province that has a higher prevalence of a chronic renal disease of unknown etiology. This kidney disease is prevalent among middle-aged farmers. Although dehydration is a possible contributor to his acute renal failure, he was well-hydrated during the initial admission, and his urine output remained normal. Additional ingredients in the formulation may have had an effect. Product data indicates 4.5% propylene glycol, but the dose and the clinical presentation do not suggest glycol toxicity.¹ Other unknown formulation constituents contributing to the renal effects cannot be ruled out. Another possibility is that humans may be more prone to the development of renal toxicity, as there appears to be species difference in susceptibility in animal studies.³