Phenol hepatic toxicity

No MRLs were derived for inhalation exposure to phenol. Human inhalation studies of phenol alone were not identified. Inhaled phenol is a respiratory irritant in animals and decreased respiration rate in mice by 50% during a 5-minute exposure at 166 ppm (De Ceaurriz et al. 1981). Based on their studies in mice, De Ceaurriz et al. (1981) estimated that a level of 2 ppm would be aNOAEL for respiratory effects in humans. A study in rhesus monkeys, rats, and mice did not find significant effects following a 90-day continuous exposure at 5 ppm (Sandage 1961). Intermittent exposure of guinea pigs and rabbits to 26-52 ppm phenol resulted in severe respiratory, cardiovascular, hepatic, and renal toxicity (Deichmann et al. 1944). Similar effects were not observed in rats exposed in a similar manner. 

Phenol is catabolized by liver microsomal monooxygenases to hydroxylated products (e.g., 1,4-dihydroxybenzene) that can undergo further conversion to a variety of electrophilic substances (e.g., benzoquinones). Such reactions may be involved in generating reactive toxic intermediates in the liver (Eastmond et al. 1986 Lunte and Kissinger 1983 Subrahmanyam and O Brien 1985). Based on the available data, hepatic effects are unlikely to occur at the exposure levels found in the environment or near hazardous waste sites. 

The benzene metabolites hydroquinone and muconic dialdehyde can produce hematotoxic effects (Eastmond et al. 1987 Gad-El Karim et al. 1985 Latriano et al. 1986). The co-administration of phenol (75 mg/kg/day) and hydroquinone (25-75 mg/kg/day) twice daily for 12 days to B6C3Fj mice produced myelotoxicity similar to that induced by benzene (Eastmond et al. 1987). The proposed mechanism suggested that selective accumulation of hydroquinone occurred in the bone marrow after the initial hepatic conversion of benzene to phenol and hydroquinone. Additionally, phenol is thought to stimulate the enzymatic activity of myeloperoxidase, which uses phenol as an electron donor, thus producing phenoxy radicals. These radicals further react with hydroquinone to form 1,4-benzoquinone, a toxic intermediate that inhibits critical cellular processes (Eastmond et al. 1987). 

Systemic adverse effects can occur through absorption from intact skin or wounds, by ingestion, or by absorption of vapor through the skin or via the lungs. They include central nervous stimulation followed by depression, seizures, coma, tachycardia, hypotension, dysrhjdhmias, pulmonary edema, metabolic acidosis, and hepatic and renal injury. Serious adverse reactions due to percutaneous absorption can occur and death has been described several times. The signs and symptoms of phenol toxicity have been reviewed (3-7) and are listed in Table 1. 

Lip Eyelid formula is a phenol peel that I first developed to increase dermatological safety and to achieve results without any occlusion on the sensitive skin of the eyelids. The same solution was then applied to the wrinkles around the mouth and then to the whole face, but with 24 hours occlusion in these two indications. It is an oil solution of phenol at over 60%. Four different oils are used in the various stages of the product s preparation. The aim of the oily formulation is to slow down the penetration of the phenol through the skin and to improve dermal and epidermal maceration. It limits the toxicity of phenol by saturating the biochemical hepatic detoxification pathways more slowly. 

When intoxication has been severe and death narrowly avoided, jaundice and oliganuria follow - a sign of the hepatic and renal toxicity of phenol. These cases do not fall... 

Some cases of hepatic and renal toxicity after severe poisoning with phenol derivatives have been reported in the literature, but I have not been able to find any such record in medical publications dealing with phenol peels. 

Clinical manifestation. It includes several syndromes a) pulmotoxic and irritative syndrome - expressed by catarrhal changes on the contact mucosa and respiratory tract, toxic pulmonary oedema b) hemotoxic syndrome - expressed by severe hemolysis of different degrees, in the severe forms - hemolytic shock and anaemia c) hepatal syndrome - characterised by subicterus or icterus, increased liver and bilirubinaemia d) renal syndrome - by oliguria or anuria, pathological deviations in the urine and acute kidney insufficiency. In the extremely severe forms consciousness is disordered. Laboratory blood and urine chemical tests show evidence of phenol metabolites, data for blood damage (increased values of free hemoglobin, reduced number of erythrocytes), positive liver tests etc. 

Phenol peels are categorized as deep peels. Similar to TCA, phenol works through protein denaturation and coagulation. However, phenol differs from TCA in that it penetrates quickly to the level of the reticular dermis. Phenol is partially detoxified by the liver and excreted through the kidneys. Percutaneous absorption of phenol can lead to rapid elevation of serum phenol levels, resulting in systemic toxicity and cardiac arrhythmias. Therefore, all patients should be cleared from a cardiac, hepatic, and renal standpoint preoperatively. In addition, intraoperative cardiac monitoring is imperative. 

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