Formaldehyde

Primary irritant effects of formaldehyde

The minimum amount of formaldehyde that can be detected by odor varies considerably between individuals and ranges from 0.1 to 1.0 ppm (0.12–1.2 mg/m ³ ), close to the concentration at which minimal irritant effects are felt in the eyes and in the pulmonary airways [ ]. Thus, the fundamental toxicity of formaldehyde lies in primary irritation to the eyes, nose, and throat when the subject is exposed to concentrations in the range of 1–5 ppm. Concentrations above 2–5 ppm cause irritation of the pharynx, lungs, and eyes, and some erythema of vaporized areas of the skin, such as the face and neck. Acute exposure to concentrations of formaldehyde of the order of three times the maximum threshold of detection of the odor will most likely produce severe acute pulmonary edema after only a few minutes.

Acute toxicity after local administration of formaldehyde-containing solutions

Dilute solutions of 1–10% formalin have been instilled into the bladder to treat inoperable profusely bleeding tumors or intractable hemorrhagic cystitis. Anuria was a severe complication. This was due either to edematous obstruction of the ureter or to tubular or papillary necrosis, probably caused by systemic absorption. Bladder perforation with intraperitoneal spillage, peritonitis, and finally death was described in an elderly patient with a carcinoma of the uterine cervix [ ].

In 1983, Godec and Gleich reviewed all published results of treatment of intractable hematuria with formalin. Dilutions of 1–10% formalin (containing 0.37–3.7% formaldehyde) were used; the most commonly used concentration of formalin was 10%. The authors concluded that formalin was probably the most effective tool for controlling massive hematuria, but also probably the most dangerous. The review covered 23 articles and 118 patients; in 104 cases, treatment was successful. However, in only 10 reports had the treatment been used without serious adverse effects; the other 13 articles listed four deaths and many serious local and systemic complications. The complication rate increased when the formalin concentration was higher, but the contact time and the volume instilled did not influence the occurrence of adverse effects. The most frequent local complications were reflux and hydronephrosis. Fibrosis of the bladder with reduced capacity was the usual clinical outcome. A systemic effect was tubular necrosis with anuria, with two deaths. Another complication was ureteric obstruction, which was not related to ureteric fibrosis or bladder wall fibrosis obstructing the intramural ureter; in two cases the obstruction appeared to be due to retroperitoneal fibrosis [ ].

In 1989, Donahue and Frank [ ] published a systematic review of 235 cases of intravesical hemorrhagic cystitis treated with intravesical instillations of diluted formalin in concentrations of 1, 5, or 10%. Complete response rates were 71%, 78%, and 83% respectively. The average duration of a complete response was 3–4 months; the recurrence rate fell gradually with the use of higher concentrations. Complications were divided into two groups: “minor complications” included all mild or transient problems not requiring surgical intervention (fever, tachycardia, transient or minor rises in blood urea nitrogen or creatinine, mild hydronephrosis, grades I and II uricourethral reflux, increased urinary frequency, urgency, incontinence, suprapubic pain, or a reduction in bladder capacity not requiring urinary diversion); “major complications” were those that required surgical intervention, resulting in loss of renal function or causing damage to the supravesical urinary tracts (stricture formation), including anuria, acute tubular necrosis, papillary necrosis, ureteric or retroperitoneal fibrosis, uterovesical or uteropelvic junction obstruction, severe hydronephrosis, grades III or IV vesicoureteric reflux, any vesical fistula, or a reduction in bladder capacity requiring urinary diversion. Major complications occurred in all treatment groups, including those treated with 1% formalin. The higher rate observed with 10% formalin was not significantly different from the rates associated with the use of 1 or 5% formalin. The mortality rates were 2.2% in all the formalin groups, but the rates were not significantly different. Formalin 10% resulted in a higher and favorable response rate, a lower recurrence rate, equal numbers of major complications and mortality rate, and a three-fold higher rate of minor complications than 5% formalin in patients with hemorrhagic cystitis due to radiotherapy for bladder tumors. In contrast, formalin 5% was more effective than formalin 10% in treating patients with intractable hematuria due to unresectable bladder tumors or cyclophosphamide-induced cystitis.

The use of 2 or 4% formaldehyde as a scolecidal agent for injection into hydatid cysts and for peritoneal lavage was followed by shock in seven cases and resulted in death in three. All three patients who died had undergone a peritoneal lavage with 2–8 liters of 2 or 4% formaldehyde [ ].