Phenol

NCI Carcinogenesis Bioassay (oral); No Evidence: mouse, rat NCITR*    National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD 20014) No. NCI-CG-TR-203 ,1980. . EPA Extremely Hazardous Substances List. Community Right-To-Know List. Reported in EPA TSCA Inventory. EPA Genetic Toxicology Program.

OSHA PEL: TWA 5 ppm (skin)
ACGIH TLV: TWA 5 ppm (skin); BEI: 250 mg(total phenol)/g creatinine in urine at end of shift; Not Classifiable as a Human Carcinogen
DFG MAK: Confirmed Animal Carcinogen with Unknown Relevance to Humans; BAT: 300 mg/L at end of shift
NIOSH REL: (Phenol) TWA 20 mg/m³; CL 60 mg/m³/15M
DOT Classification:  6.1; Label: Poison

For occupational chemical analysis use OSHA: #32 or NIOSH: Phenol, 3502; Phenol and p-Cresol in Urine, 8305.

The Phenol, monohydroxy derivative of benzene, is an organic compound with the chemical formula C₆H₅OH. It has the EINECS register number 203-632-7 and CAS register number 108-95-2. Phenol is appreciably soluble in water, with about 8.3 g dissolving in 100 mL (0.88 M). In addition, Phenol is a colourless crystals with a characteristic odour. It is stable which should be protected from strong oxidizing agents, strong bases, strong acids, alkalies and calcium hypochlorite. Phenol is flammable which may discolour in light. 

Properties: Phenol is slightly acidic which reacts completely with aqueous NaOH to lose H⁺, whereas most alcohols react only partially. However, Phenol is less acidic than carboxylic acids, and even carbonic acid. Phenol can be deprotonated with moderate base such as triethylamine, forming the nucleophilic phenoxide anion or phenolate anion. This material is a systemic poison and constitutes a serious health hazard.

The risks of using Phenol in the laboratory must be fully assessed before work begins. Phenol can occur exposures in the workplace, from environmental media, from contaminated drinking water or foodstuffs, or from use of consumer products containing phenol. Phenol is highly reactive toward electrophilic aromatic substitution as the oxygen atom's pi electrons donate electron density into the ring. Phenol exhibits keto-enol tautomerism with its unstable keto tautomer cyclohexadienone, but only a tiny fraction of phenol exists as the keto form. Phenol therefore exists entirely in the enol form.

Preparation: Phenol has been made, over the years, by a variety of processes. Historically, an important method was the sulfonation of benzene followed by desulfonation with caustic soda:

C₆H₆ + H₂SO₄ → C₆H₅SO₃H + H₂O
C₆H₅SO₃H + 2 NaOH → C₆H₅OH + Na₂SO₄

The above route to Phenol has no longer used. The principal process in use is the peroxidation of cumene (iso-propylbenzene) at 130 °C in the presence of air and a catalyst followed by decomposition of the peroxide at 55 to 65 °C in the presence of sulfuric acid. In the cumene process, cumene is oxidized to form cumene hydroperoxide that is then concentrated and cleaved to produce phenol and acetone. By-products of the oxidation reaction are acetophenone and dimethyl benzyl alcohol, which is dehydrated in the cleavage reaction to produce alpha-methylstyrene.

C₆H₆ + CH₂=CH-CH₃ → C₆H₅CH(CH₃)₂
C₆H₅CH(CH₃)₂ + O₂ → C₆H₅C(CH₃)₂OOH
C₆H₅C(CH₃)₂OOH [H₂SO₄]→ C₆H₅OH + CH₃COCH₃

The toluene-benzoic acid process of preparation of Phenol involves three chemical reactions: (l) oxidation of toluene to form benzoic acid, (2) oxidation of benzoic acid to form phenyl benzoate, (3) hydrolysis of phenyl benzoate to form phenol.

2 C₆H₅CH₃ + 3 O₂ → 2 C₃H₅CO₂H + 2 H₂O
4 C₆H₅CO₂H + O₂ → 2 C₆H₅CO₂C₆H₅ + 2 H₂O + 2 CO₂
C₆H₅CO₂C₆H₅ + 2 OH^- → 2 C₆H₅OH + CO₂

Uses: Phenol was widely used as an antiseptic, especially as Carbolic soap. Phenol is also used in the preparation of cosmetics including sunscreens, hair dyes, and skin lightening preparations. The major uses of Phenol involve its conversion to plastics or related materials. Condensation with acetone gives bisphenol-A. Phenol is also used as an oral anesthetic/analgesic, commonly used to temporarily treat pharyngitis. Phenol is also a versatile precursor to a large collection of drugs, most notably aspirin but also many herbicides and pharmaceuticals. Phenol is one of the chemicals for embalming bodies for study because of its ability to preserve tissues for extended periods of time.

When you are using Phenol, please be cautious about it. Phenol is toxic, harmful, corrosive and highly flammable. There will be a danger of serious damage to health by prolonged exposure through inhalation, and in contact with skin and if swallowed. In addition, Phenol is toxic by inhalation, in contact with skin and if swallowed. What's more, there is a danger of very serious irreversible effects through inhalation, in contact with skin and if swallowed.

In case of contact with eyes, you should rinse immediately with plenty of water and seek medical advice. Whenever you will contact Phenol, you should wear suitable protective clothing, gloves and eye/face protection. In case of accident or if you feel unwell, you can seek medical advice immediately (show label where possible). Meanwhile, you must avoid contact with skin and eyes.

Descriptors computed from structure of Phenol:
(1)Canonical SMILES: C1=CC=C(C=C1)O
(2)InChI: InChI=1S/C6H6O/c7-6-4-2-1-3-5-6/h1-5,7H
(3)InChIKey: ISWSIDIOOBJBQZ-UHFFFAOYSA-N

Toxicity of Phenol:

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
cat	LDLo	oral	80mg/kg (80mg/kg)		"Abdernalden's Handbuch der Biologischen Arbeitsmethoden." Vol. 4, Pg. 1319, 1935.
cat	LDLo	subcutaneous	80mg/kg (80mg/kg)		Journal of Pharmacology and Experimental Therapeutics. Vol. 80, Pg. 233, 1944.
cat	LDLo	unreported	250mg/kg (250mg/kg)		Revue Medicale de la Suisse Romande. Vol. 15, Pg. 561, 1895.
dog	LDLo	oral	500mg/kg (500mg/kg)		"Abdernalden's Handbuch der Biologischen Arbeitsmethoden." Vol. 4, Pg. 1319, 1935.
dog	LDLo	unreported	200mg/kg (200mg/kg)		Revue Medicale de la Suisse Romande. Vol. 15, Pg. 561, 1895.
frog	LDLo	parenteral	290mg/kg (290mg/kg)	PERIPHERAL NERVE AND SENSATION: SPASTIC PARALYSIS WITH OR WITHOUT SENSORY CHANGE BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD CARDIAC: OTHER CHANGES	Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. Vol. 166, Pg. 437, 1932.
frog	LDLo	subcutaneous	75mg/kg (75mg/kg)		"Abdernalden's Handbuch der Biologischen Arbeitsmethoden." Vol. 4, Pg. 1319, 1935.
frog	LDLo	subcutaneous	290mg/kg (290mg/kg)		"Handbook of Toxicology," 4 vols., Philadelphia, W.B. Saunders Co., 1956-59Vol. 1, Pg. 228, 1955.
guinea pig	LDLo	intraperitoneal	300mg/kg (300mg/kg)		"Handbook of Toxicology," 4 vols., Philadelphia, W.B. Saunders Co., 1956-59Vol. 1, Pg. 228, 1955.
guinea pig	LDLo	subcutaneous	450mg/kg (450mg/kg)		"Handbook of Toxicology," 4 vols., Philadelphia, W.B. Saunders Co., 1956-59Vol. 1, Pg. 228, 1955.
human	LDLo	oral	140mg/kg (140mg/kg)	BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS" SKIN AND APPENDAGES (SKIN): SWEATING: OTHER	"Practical Toxicology of Plastics," Lefaux, R., Cleveland, OH, Chemical Rubber Co., 1968Vol. -, Pg. 329, 1968.
human	LDLo	oral	14gm/kg (14000mg/kg)	BEHAVIORAL: MUSCLE WEAKNESS LUNGS, THORAX, OR RESPIRATION: CYANOSIS	"Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969Vol. -, Pg. 463, 1969.
infant	LDLo	oral	10mg/kg (10mg/kg)	BEHAVIORAL: MUSCLE WEAKNESS LUNGS, THORAX, OR RESPIRATION: CYANOSIS	"Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969Vol. -, Pg. 463, 1969.
mammal (species unspecified)	LD50	oral	500mg/kg (500mg/kg)		Gigiena Truda i Professional'nye Zabolevaniya. Labor Hygiene and Occupational Diseases. Vol. 32(10), Pg. 25, 1988.
man	TDLo	unreported	5714ug/kg (5.714mg/kg)	SENSE ORGANS AND SPECIAL SENSES: OTHER CHANGES: OLFACTION	Veterinary and Human Toxicology. Vol. 41, Pg. 151, 1999.
mouse	LC50	inhalation	177mg/m3 (177mg/m3)		Gigiena i Sanitariya. For English translation, see HYSAAV. Vol. 41(6), Pg. 103, 1976.
mouse	LD50	intraperitoneal	180mg/kg (180mg/kg)		Pharmacologist. Vol. 10, Pg. 172, 1968.
mouse	LD50	intravenous	112mg/kg (112mg/kg)	BEHAVIORAL: TREMOR	Quarterly Journal of Pharmacy & Pharmacology. Vol. 12, Pg. 212, 1939.
mouse	LD50	oral	270mg/kg (270mg/kg)		Gigiena i Sanitariya. For English translation, see HYSAAV. Vol. 38(8), Pg. 6, 1973.
mouse	LD50	subcutaneous	344mg/kg (344mg/kg)		Industrial Health. Vol. 5, Pg. 143, 1967.
rabbit	LD50	skin	630mg/kg (630mg/kg)		Union Carbide Data Sheet. Vol. 1/6/1966,
rabbit	LDLo	intraperitoneal	620mg/kg (620mg/kg)		Journal of Pharmacology and Experimental Therapeutics. Vol. 80, Pg. 233, 1944.
rabbit	LDLo	intravenous	180mg/kg (180mg/kg)		Journal of Pharmacology and Experimental Therapeutics. Vol. 80, Pg. 233, 1944.
rabbit	LDLo	oral	420mg/kg (420mg/kg)		Journal of Pharmacology and Experimental Therapeutics. Vol. 80, Pg. 233, 1944.
rabbit	LDLo	subcutaneous	620mg/kg (620mg/kg)		Journal of Pharmacology and Experimental Therapeutics. Vol. 80, Pg. 233, 1944.
rabbit	LDLo	unreported	150mg/kg (150mg/kg)		Revue Medicale de la Suisse Romande. Vol. 15, Pg. 561, 1895.
rat	LC50	inhalation	316mg/m3 (316mg/m3)		Gigiena i Sanitariya. For English translation, see HYSAAV. Vol. 41(6), Pg. 103, 1976.
rat	LD50	intraperitoneal	127mg/kg (127mg/kg)		Food and Chemical Toxicology. Vol. 22, Pg. 665, 1984.
rat	LD50	oral	317mg/kg (317mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Proceedings of the Society for Experimental Biology and Medicine. Vol. 32, Pg. 592, 1935.
rat	LD50	skin	669mg/kg (669mg/kg)	BEHAVIORAL: TREMOR KIDNEY, URETER, AND BLADDER: HEMATURIA SKIN AND APPENDAGES (SKIN): CUTANEOUS SENSITIZATION (EXPERIMENTAL): AFTER TOPICAL EXPOSURE	British Journal of Industrial Medicine. Vol. 27, Pg. 155, 1970.
rat	LD50	subcutaneous	460mg/kg (460mg/kg)		Toho Igakkai Zasshi. Journal of Medical Society of Toho University. Vol. 10, Pg. 1, 1963.