Phenol

Endpoint summary

Description of key information

In humans and experimental animals the signs and symptoms of acute toxicity are similar regardless of the route of administration (compare also with data presented in the Summary of Section 7.1). Beside the concentration dependent local effects (corrosive properties of phenol) also systemic effects are obvious. Muscle weakness, convulsions, and coma are the predominant symptoms associated with exposure to lethal concentrations of phenol. Regardless of the route of exposure, absorption is rapid, as illustrated by the fact that acute doses of phenol can produce symptoms of toxicity within minutes after administration. 
For animals, dermal and oral LD50 values are reported in the literature falling within one order of magnitude: oral LD50 in rats 340 -650 mg/kg bw and dermal LD50 in rats 660 (525 -707) mg/kg bw and in rabbits 850 mg/kg bw. Although LC50 values are not available in literature, rats are reported to have tolerated phenol concentrations as high as 236 ppm (900 mg/m³) for 8 hours, resulting in ocular and nasal irritation, loss of coordination. The odour recognition threshold (100% response) of phenol in humans is approximately 0.05 ppm, a concentration far below the levels where toxic effects have been reported; thus, the chemical has good warning properties for inhalation exposure. 
Oral toxicity of phenol in humans leading to the death of the victim is reported for doses as low as 140-290 mg/kg body weight. Absorption from spilling phenolic solutions on the skin of humans may be very rapid, and death results from collapse within 30 minutes to several hours. Death has resulted from absorption of phenol through a skin area of 64 inch². 
Based on these data phenol has been classified as “toxic” and labelled with “R 23/24/25 (Toxic by inhalation, in contact with skin and if swallowed)”. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

340 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

660 mg/kg bw

Additional information

No studies are available which are conducted according to the current guideline. However, the acute toxic effects of phenol aerosols (vehicle water) were investigated using one dose level of nominal 900 mg/m³ and an exposure duration of 8 h (Flickinger, 1976; see robust study summary in IUCLID Section 7. Data on acute toxicity of phenol is presented in the EU-RAR (2006) in Section 4.1.2.2.1 (animal studies; page 81ff) and in Section 4.1.2.2.2 (human data; page 84ff). It is stated that signs of acute toxicity in humans and experimental animals are similar regardless of the route of administration. Lethal doses in humans after oral or dermal exposure were given as well as LD50/LC50 values in experimental animals. Phenol has been classified as “toxic” and labelled with “R 23/24/25 (Toxic by inhalation, in contact with skin and if swallowed)”.

 

ACUTE ORAL TOXICITY

In rats the following LD50 values were reported: 340-540 mg/kg bw (male & female rats combined; Deichmann and Witherup, 1944; see robust study summary in IUCLID Section 7.2.1) 650 mg/kg bw (male rats; Flickinger, 1976; see robust study summary in IUCLID Section 7.2.1). Systemic signs of toxicity occurred immediately after application: Twitching in muscles; fluctuating body temperature (mostly subnormal); pulse and respiration rate increased and then became slow, irregular and weak; pupils first contracted and later on dilated; salivation, marked dyspnea, tremor and convulsions before death. Rats died 3-150 minutes after oral administration. In mice similar LD50 values were reported: approximately 300 mg/kg bw (von Oettingen and Sharpless, 1946). Studies in rabbits with different concentration of phenol in water have shown that the (systemic) toxic effects are independent on the concentration used (Deichmann and Witherup, 1944).

 

ACUTE INHALATION TOXICITY

No mortality was reported but ocular and nasal irritation as well as coordination loss and tremor during the exposure period. The rats appeared normal the next day. No effects were found on body weight gain and necropsy revealed no lesions attributable to inhalation of the aerosol. The LC50 should be > 900 mg/m³.

In a sensory irritation test with male mice a RD50 (concentration associated with a 50% decrease in respiratory rate) of 166 ppm was detected for phenol, uncomfortable but tolerable concentration was found at 17 ppm and minimal or no effect was detected at a concentration of 2 ppm (de Ceaurriz et al., 1981).

 

ACUTE DERMAL TOXICITY

The dermal LD50 in male rabbits in an acute dermal toxicity study was 850 mg/kg bw; the rabbits received dermal administration of phenol preparations in water for max. 24 h. Animals died the first day after application. The aqueous solution of phenol produced necrosis of the skin in all of the exposed rabbits (no data on systemic clinical signs; Flickinger, 1976; see robust study summary in IUCLID Section 7.2.3).

Five female Alderly Park rats per dose received dermal application of molten phenol at dose levels of 1.0, 0.5, 0.25 or 0.1 ml phenol/kg bw (1st trial, occlusive) or in the 2nd trial (uncovered) of 1.0, 0.75, 0.3 and 0.1 ml/kg bw. Exposure was terminated after 24 h by washing with a mild detergents. The post exposure observation period was 7 days. Necropsy was performed as well as histopathology of skin and kidney. In the 1st trial all rats died at a dose of 1 ml/kg bw and 2 rats at 0.5 ml/kg bw within 4 h; in the 2nd trial all rats died at 1 or 0.75 ml/kg bw within 24 h. Local effects included severe skin lesions with immediate onset of oedema followed within 4 hours by necrosis associated at 24 hours with discoloration and surrounding erythema. Systemic effects: all the animals behaved similarly; between 5-10 minutes after dosing they developed severe muscle tremors causing marked twitching which developed into generalised convulsions with loss of consciousness and prostration. At varying times between 45-90 minutes, depending upon the dose administered, the animals developed severe haemoglobinuria. Necropsy revealed renal congestion and the urinary bladders were distended with blood-stained fluid. Kidneys showed in histopathology haematin casts in the distal convoluted tubules and in the tubules of the medulla and papillae. The skin showed extensive epidermal necrosis characterised by a hyaline appearance of the cells, loss of intercellular processes, and deposition of eosinophilic debris in the intercellular spaces. There was extensive superficial necrosis of the dermis, which was stained a purple colour by haematoxylin and eosin suggesting a coagulative type necrosis. In this study the dermal LD50 in female rats was 660 mg/kg bw. (Conning and Hayes, 1970; robust study summary in IUCLID Section 7.2.3).

Brown et al. (1975) reported a dermal LD50 of 525 mg/kg bw in rats and Vernot et al. (1977) in rabbits a dermal LD50 of 1400 mg/kg bw (additional information in IUCLID Section 7.2.3).

 

DATA ON HUMANS (see IUCLID Section 7.10.3)

Liquid phenol in contact with the skin rapidly enters the bloodstream. From a variety of case reports clinical signs are known being documented for various occupationally exposed persons. These signs and symptoms can develop rapidly with serious consequences including shock, collapse, coma, convulsions, cyanosis, damage to internal organs, and death. Skin contact of humans with solutions, emulsions, or preparations containing 80-100% phenol for 5-30 minutes has been reported to result in death (NIOSH, 1976).

Phenol is reported to cause poisoning by skin absorption, vapour inhalation and ingestion (Kania, 1981). Primary route of entry is the skin. Vapours readily penetrate the skin surface with absorption efficiency equal to that of inhalation. Absorption from spilling phenolic solutions on the skin may be very rapid, and death results from collapse within 30 minutes to several hours. Death has resulted from absorption of phenol through a skin area of 64 inch². Where death is delayed, damage of the kidneys, liver, pancreas and spleen, and oedema of the lungs may result. The symptoms develop rapidly, frequently within 15-20 minutes following spilling of phenol on the skin. Initial skin contact produces a white wrinkled discoloration with no experience of pain due to the local anaesthetic properties of phenol, with the affected area turning brown and subsequently becoming gangrenous. Prolonged exposure may result in deposition of dark pigment (ochronosis). Phenol vapours are also well absorbed by the lungs. Inhalation causes dyspnea, cough, cyanosis, and pulmonary oedema. Ingestion of even small amounts of phenol causes severe burns of the mouth, esophagus, and abdominal pain. Patches, first white then brown with areas of necrosis, may be noted about the face and oral cavity (Kania, 1981).

Oral toxicity of phenol in humans leading to the death of the victim is reported for doses as low as 140-290 mg/kg body weight (Bruce et al., 1987).

The odour recognition threshold (100% response) of phenol is approximately 0.05 ppm (EU-RAR, 2006).

Justification for classification or non-classification

Based on the above reported data phenol has been classified as “toxic” and labelled with “R 23/24/25 (Toxic by inhalation, in contact with skin and if swallowed)”.