Acute renal and hepatic failure due to accidental percutaneous absorption of 1,2-dichlorpropane contained in a commercial paint fixative

Enrico Fiaccadori, Umberto Maggiore, Carlo Rotelli, Roberto Giacosa, Diego Ardissino1, Giuseppe De Palma, Enrico Bergamaschi and Antonio Mutti

Dipartimento di Clinica Medica Nefrologia & Scienze della Prevenzione Università degli Studi di Parma 1 Unità Operativa di Cardiologia Azienda Ospedaliera-Universitaria Parma Parma Italy Email: enrico.fiaccadori{at}unipr.it

Sir,

1,2-dichloropropane (DCP), a colourless, flammable liquid with a chloroform-like odour, is a volatile organo-halogenated compound contained in many commercial chemicals, such as solvents for oils, waxes, resins and glues, degreasing and dry-cleaning fluids, pesticides, lead scavengers for gasoline, and paint fixatives [1].

In the few cases of acute severe 1,2-DCP toxicity reported so far in humans, toxic damage has involved the kidney, liver, haemostatic system, red blood cells and CNS, but in every instance, intoxication occurred through the inhalatory or oral route [13].

Here we describe the case of a patient with severe acute 1,2-DCP intoxication that occurred through the percutaneous route. In this patient, the severity of 1,2-DCP toxicity might have been made worse by a genetically based susceptibility.

Case. Two hours after admission to the Coronary Care Unit for symptomatic wide-complex tachiarrythmia, a 46-year-old jaundiced man was transferred to our Renal Intensive Care Unit (ICU) because the arrhythmia was found to be associated with hyperkalaemia (serum potassium 7.0 mmol/l), lactic acidosis (lactic acid 4.2 mmol/l) and oliguric acute renal failure (serum creatinine 769 µmol/l, urea nitrogen 26 mmol/l); other relevant laboratory data were compatible with acute hepatocellular necrosis, rhabdomyolysis and severe disseminated intravascular coagulation.

The past history of the patient was unremarkable, except for a hypertrophic cardiomiopathy on beta-blocker therapy. He manifested with progressive oliguria, malaise, nausea and jaundice in the previous 4 days, and denied consumption of hepato- or nephrotoxic drugs, new medications, illicit drugs or mushrooms, or exposure to Leptospira species, which is endemic in our area. He drank alcohol infrequently. Further inquiry revealed that the present illness appeared shortly after the patient had been painting for 6 h outdoors with a commercial paint fixative containing 1,2-DCP (35–40%) and toluene (33–38%). The chemical accidentally spilled from its container onto the patient's upper trunk and abdomen. After contamination, the patient waited 5 h before removing his clothes and washing himself, and reported only transient skin reddening on the cutaneous areas involved.

Once the patient was transferred to the Renal ICU, urgent haemodialysis was begun, along with the administration of fresh frozen plasma and antithrombin III. Sinus rhythm was restored after 30 min from the beginning of renal replacement therapy. Transthoracic echocardiography showed left ventricular hypertrophy and an ejection fraction of 70%. Renal ultrasonographic findings were normal. Acute renal failure became non-oliguric after two 10-h sessions of sustained low-efficiency dialysis in 2 days; coagulation tests returned to normal values after 48 h, and the patient was discharged to his home after 7 days, with follow-up at our unit. Renal and hepatic function recovered fully after 2 weeks. Serology for hepatitis A, B and C viruses, human immunodeficiency virus, and for antinuclear and antimitochondrial antibodies was negative. We investigated the role of individual susceptibility factors in the development of the above clinical outcomes. The genotypes of polymorphic enzymes relevant to organo-halogenated compound metabolism—glutathione S-transferases M1-1 (GSTM1) and T1-1 (GSTT1)—were characterized in DNA extracted from peripheral venous blood [4]. The patient showed a combination of GSTM1- and GSTT1-positive genotypes, which have a prevalence of 50 and 15%, respectively, in the Caucasian population [6]. GSTM1- and GSST1-positive subjects have a full reduced glutathione conjugative capability, potentially resulting in more efficient production of toxic derivatives [57].

Comment. In the cases reported so far, 1,2-DCP poisoning in man has occurred through inhalation or ingestion [13]. Clinical manifestations include irritation of the mucous membranes in mild cases, but also headache, dizziness and unconsciousness in more severe cases. Acute kidney damage and liver damage, as well as severe haemolytic anaemia and consumption coagulopathy have also been reported [13]. Most of the chemical (80–90%) is excreted in the expired air, urine and faeces within 24 h of acute intoxication, and symptoms may not manifest until this time period has elapsed [1].

Because our patient had been working outdoors in a well ventilated environment, without reporting signs or symptoms of upper respiratory tract irritation during or immediately after painting, it is highly unlikely that massive intoxication with 1,2-DCP occurred via inhalation. Rather, due to the extensive and prolonged skin contact with the paint fixative, percutaneous absorption represents the most plausible mechanism for 1,2-DCP poisoning. However, we cannot exclude that additional mechanisms might have played an important role in the present case. First, the patient's genotypes (GSTM1 and GSTT1) may have contributed to aggravation of 1,2-DCP toxicity by allowing more efficient coniugation of the chemical, resulting in increased production of toxic derivatives [57]. Secondly, defatting of the skin caused by prolonged and/or repeated contact with 1,2-DCP, which is a degreasing compound, may have promoted a more rapid entrance of 1,2-DCP itself into the patient's body. Thirdly, the patient was also exposed to toluene, which was contained in the paint fixative along with 1,2-DCP. Toluene is also a degreasing compound, thus it might potentially facilitate percutaneous absorption of coexistent toxicants. However, it is unlikely that toluene is responsible for the severe clinical manifestations observed in this case, since it has been shown that short-term occupational exposures to toluene can lead only to transient and reversible haematuria, type 1 renal tubular acidosis and hypokalaemia [8].

In conclusion, the present report documents that severe systemic toxicity, including acute renal and hepatic failure, can result from massive percutaneous absorption of 1,2-DCP; moreover, genetic factors could also have contributed to aggravate the clinical expression of 1,2-DCP toxicity.

In the light of the wide use of 1,2-DCP-containing compounds, clinicians should be aware of the habits and modalities of exposure to these chemicals, as they represent a dangerous and under-recognized source of life-threatening intoxication.

References

  1. Hazardous Substances Databank (HSDB). 1,2-dichloropropane. HSDB number 1102, last revision date December 2, 2001. Available online at http://www.toxnet.nlm.nih.gov. Accessed May 1,2002
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  3. Pozzi C, Marai P, Ponti R et al. Toxicity in man due to stain removers containing 1,2-dichloropropane. Br J Industr Med1985; 42:770–772[ISI][Medline]
  4. Arand M, Muhlbauer R, Hengstler J. A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem1996; 236:184–186[CrossRef][ISI][Medline]
  5. Lock EA. Mechanism of nephrotoxic action due to organohalogenated compounds. Toxicol Lett1989; 46:93–106[CrossRef][ISI][Medline]
  6. Anders MW, Dekant W. Glutathione dependent bioactivation of haloalkenes. Annu Rev Pharmacol Toxicol1998; 38:501–537[CrossRef][ISI][Medline]
  7. Cooper AJL. Enzymology of cysteine S–coniugate beta-lyases. Adv Pharmacol1994; 27:71–113[Medline]
  8. Hazardous Substances Databank (HSDB). Toluene. HSDB number 131, last revision date January 31, 2001. Available online at http://www.toxnet.nlm.nih.gov. Accessed May 1,2002




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