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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 342
CCOHS Chemical Name: Hydroquinone

Synonyms:
Benzohydroquinone
1,4-Benzenediol
p-Benzenediol
Dihydroxybenzene
1,4-Dihydroxybenzene
p-Dihydroxybenzene
HQ
Hydroquinol
p-Hydroquinone
p-Hydroxyphenol
Quinol
Paradioxybenzène

Chemical Name French: Hydroquinone
Chemical Name Spanish: Hidroquinona

Trade Name(s):
Eldopaque
Eldoquin
Quinnone
Tecquinol

CAS Registry Number: 123-31-9
UN/NA Number(s): 2662 3435
RTECS Number(s): MX3500000
EU EINECS/ELINCS Number: 204-617-8
Chemical Family: Aromatic alcohol / hydroxybenzene / phenol / aromatic diol / dihydroxybenzene
Molecular Formula: C6-H6-O2
Structural Formula: HO-C6H4-OH

SECTION 2. DESCRIPTION

Appearance and Odour:
White or colourless, odourless, crystalline solid when pure. (1,5,31) Commercial grades are typically white, off-white, light tan or light grey crystalline solids.(31)

Odour Threshold:
Hydroquinone is odourless. Alkaline solutions readily form 1,4- benzoquinone which has odour thresholds of 0.1 ppm (absolute perception limit) and 0.15 ppm (100% recognition) (32)

Warning Properties:
POOR- Odourless and irritation levels are poorly defined.

Composition/Purity:
Hydroquinone is available in a number of specialty grades and typically has a purity of 98.5% and above.(31,33)

Uses and Occurrences:
Hydroquinone is used mainly as a developer in black-and-white photography and related graphic arts, and medical and industrial X-ray films, for the manufacture of rubber antioxidants and antiozonants, and food antioxidants, as a polymerization inhibitor in the vinyl and acrylic monomer industry, as a stabilizer for unsaturated polyester resins, as a starting material for dyes, pigments, herbicides, and the fungicide Chloroneb, and in cosmetics, medical skin preparations and in hair dyes. It is also used in boiler water treatment, as a monomer for the preparation of a variety of polymers, as a reagent in the determination of small quantities of phosphate, and as a stabilizer in paints, varnishes, motor fuels and oils.(1,31,33,34)
Hydroquinone occurs naturally in bacteria, plants and some animals. It occurs as a natural component of plant-derived beverages and food products, e.g. coffee beans, and in the leaves of several plants, e.g. cranberry and some varieties of pear.(1,31)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
White or colourless, odourless, crystalline solid when pure. Commercial grades are typically white, off-white, light tan or light grey crystalline solids. Solid can burn if strongly heated. POTENTIAL COMBUSTIBLE DUST HAZARD. Powdered material may form explosive dust-air mixtures. TOXIC. Harmful if swallowed. May cause harmful nervous system effects, including tremors and convulsions. SKIN SENSITIZER. May cause allergic skin reaction.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Pure hydroquinone does not readily form a vapour at room temperature. The dust may cause irritation of the nose, throat and upper respiratory tract. There is no human or animal information available.
In the presence of air and moisture, hydroquinone dust may react to form irritating 1,4-benzoquinone (quinone) which forms a vapour at room temperature.(1,2) The rate of this reaction depends on the pH of the medium, with alkaline solutions reacting more readily. Therefore, exposure to hydroquinone dust may involve exposure to 1,4-benzoquinone vapour which is a respiratory irritant. The degree of irritation depends on how much 1,4- benzoquinone is formed.

Skin Contact:
Hydroquinone dust is probably not irritating. Hydroquinone solutions are probably mild irritants, based on limited animal and human information. Mild irritation was observed in 6/200 volunteers following one-time application of 5, 6 and 7% solutions to the neck and behind the ears. More marked irritation was observed after two applications, 24 hours apart.(2) Redness or staining of the skin was observed following application of a 1% water solution to volunteers for 48 hours.(1)
Hydroquinone can cause an allergic skin reaction in some individuals See "Effects of Long-term (Chronic) Exposure" below for additional information.
Hydroquinone is absorbed slowly through the skin.(4) It is not likely to cause significant harmful effects by this route of exposure, based on animal information.

Eye Contact:
In the presence of air and moisture, hydroquinone may form 1,4-benzoquinone which is more irritating.(1,3,5) Direct contact with hydroquinone dust is expected to cause mild irritation, based on limited animal information. Eye irritation was observed following airborne exposure to hydroquinone with 1,4- benzoquinone present and became more severe at higher concentrations.(3)

Ingestion:
Several non-occupational case reports indicate that ingestion of large amounts can cause harmful effects on the nervous system including tremors and convulsions, dark urine, vomiting, abdominal pain, increased heart rate, coma and death.(1,2,5) There is one report of gastrointestinal disturbance, with symptoms of nausea, vomiting, abdominal cramps and diarrhea which was suspected to be due to hydroquinone contamination of drinking water.(6) Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

Lungs/Respiratory System:
No firm conclusions can be drawn from the limited information available due to the small numbers of employees studied and the lack of exposure information. Coughing and reduced lung function were observed in 33 employees exposed to hydroquinone and its derivatives, compared to non- exposed employees.(7) In a historical study, no harmful respiratory effects were observed in 88 workers exposed to high, but unspecified, concentrations of 1,4-benzoquinone and hydroquinone for up to 15 years.(1)

Skin:
Repeated or prolonged contact with hydroquinone may cause dermatitis which may involve depigmentation (white patches) and discolouration of the nails and hair.
Cases of depigmentation have been reported following long-term contact with film developing solutions containing hydroquinone.(7,8) In one case, this effect was observed in a man following contact with a very dilute solution (0.06%) for 8-9 months.(1) Irritation (redness and tingling) was observed in 32% of volunteers following application of a cream containing 5% hydroquinone for a number of weeks.(9) This effect has also been observed in animal studies.

Skin Sensitization:
Repeated or prolonged contact with hydroquinone may cause skin sensitization. Sensitized people can develop severe swelling and skin reddening following contact with hydroquinone at concentrations which do not affect unsensitized persons.
Contact allergy to hydroquinone was diagnosed in four out of seven employees exposed to film chemicals containing hydroquinone. Previous history of allergies was not discussed.(10) Skin sensitization has been observed in animal studies.
In one animal study, cross-sensitivity was observed between hydroquinone and p-methoxyphenol.(1) A case of probable cross-sensitization to hydroquinone monobenzyl ether and hydroquinone has also been reported.(1)

Liver:
No firm conclusions can be drawn from a single case report of liver effects observed following occupational exposure to a developing solution containing hydroquinone and glutaraldehyde. The effects cleared within 7 months after exposure stopped. Exposure levels were not reported.(14)

Eyes/Vision:
Historical studies have shown that long-term exposure to airborne hydroquinone dust and/or 1,4-benzoquinone dust or vapour can cause dark brown colour in the eye, inflammation, increased sensitivity to light and partial loss of vision.(1,5,7,11) These effects can be delayed for several years after exposure has ended and the degree of injury increases with the length of exposure.(1,3) In one report which provided exposure information, exposures exceeded current occupational exposure standards for both hydroquinone and 1,4-benzoquinone. The relative contribution of 1,4- benzoquinone vapour and hydroquinone dust to the development of these injuries has not been assessed.(1,3,12,13) Depigmentation, inflammation and corneal opacities have also been observed in animal studies.

Carcinogenicity:

The International Agency for Research on Cancer (IARC) has determined there is inadequate evidence for the carcinogenicity of hydroquinone to humans. There is limited evidence for the carcinogenicity of hydroquinone to experimental animals.(45)
In one study, no increase in cancer deaths was found in 879 people employed in the manufacture and use of hydroquinone between 1949 and 1990. These employees were exposed to 0.1 to 6.0 mg/m3 (mean less than 2.5 mg/m3) hydroquinone dust and to 0.1 to 0.3 ppm 1,4-benzoquinone.(8) No firm conclusions can be drawn from other studies in which employees were exposed to other chemicals at the same time, exposures to hydroquinone were minimal and/or results were not statistically significant.(1,7,8,17)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is not classifiable as to its carcinogenicity to humans (Group 3).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as an animal carcinogen (A3).

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
There is no human information available. Embryotoxic and fetotoxic effects have been observed in rats and rabbits following oral exposure, but only in the presence of maternal toxicity.

Reproductive Toxicity:
There is no human information available. No harmful effects on fertility have been observed in animal studies.

Mutagenicity:
It is not possible to conlcude that hydroquinone is mutagenic, based on the available information. There is no information available from occupationally-exposed groups. Positive results have been obtained in both germ cells and somatic cells in tests using live animals, but oral doses were toxic to the cells and other studies used a route of exposure that is not relevant to occupational situations (intraperitoneal injection).

Toxicologically Synergistic Materials:
Exposure to other phenolic compounds at the same time may increase the toxicity of hydroquinone, based on animal studies.(1)

Potential for Accumulation:
Hydroquinone is rapidly absorbed following inhalation or ingestion. It is slowly absorbed through the skin. However, when dissolved in other solvents (e.g. alcohols) it may be more quickly absorbed.(18) It is rapidly and widely distributed in the body. It is metabolized to 1,4-benzoquinone and other oxidation products. It is rapidly excreted, mainly as sulfate and glucuronide conjugates of hydroquinone, with small amounts of unchanged hydroquinone and 1,4-benzoquinone, mainly in the urine.(1,5,19)


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, remove source of contamination or have victim move to fresh air. Obtain medical advice immediately.

Skin Contact:
Avoid direct contact with this chemical. Wear chemical protective gloves, if necessary. As quickly as possible, flush contaminated area with lukewarm, gently running water for 5-10 minutes, or until the chemical is removed. Under running water, remove contaminated clothing, shoes, and leather goods (e.g. watchbands, belts). If irritation persists, repeat flushing and obtain medical attention immediately. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Avoid direct contact with this chemical. Wear chemical protective gloves, if necessary. SOLID: Do not allow victim to rub eye(s). Let the eye(s) water naturally for a few minutes. Have victim look right and left, and then up and down. If particle/dust does not dislodge, flush with lukewarm, gently flowing water for 5 minutes or until particle/dust is removed, while holding the eyelid(s) open. If irritation persists, obtain medical attention. DO NOT attempt to manually remove anything stuck to the eye(s). If irritation persists, obtain medical attention immediately. SOLUTIONS: Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes or until the chemical is removed, while holding the eyelid(s) open. If irritation persists, obtain medical attention immediately.

Ingestion:
NEVER give anything by mouth if victim if rapidly losing consciousness, is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 ozs) of water. If vomiting occurs naturally, rinse mouth and repeat administration of water. Obtain medical attention immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest). Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
165 deg C (329 deg F) (closed cup) (1,31)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not available.

Upper Flammable (Explosive) Limit (UFL/UEL):
Not available

Autoignition (Ignition) Temperature:
515-516 deg C (959-960 deg F) (5,31)

Sensitivity to Mechanical Impact:
Probably not sensitive. Stable material.

Combustion and Thermal Decomposition Products:
Toxic decomposition products.(37)

Flammable Properties:

Specific Hazards Arising from the Chemical:
During a fire irritating/toxic decomposition products may be formed.

Extinguishing Media:
Carbon dioxide, dry chemical powder, alcohol foam, polymer foam, water spray or fog.(5,37) Alcohol-resistant fire-fighting foam is recommended for use on all water-soluble materials. However, water or foam may cause frothing.(35)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid toxic decomposition products. Avoid generating dust to minimize risk of explosion.
Move containers from fire area if it can be done without risk. Water or foam may cause frothing when applied to burning molten hydroquinone. The frothing may be violent and could endanger personnel close to the fire. However, a water spray or fog that is carefully applied to the surface of the liquid, preferably with a fine spray or fog nozzle, will cause frothing that will blanket and extinguish the fire. In addition, water can be used in the form of spray or fog to prevent dust formation, absorb heat, keep containers cool and protect fire-exposed material. Solid streams of water may be ineffective and spread material.
Hydroquinone is hazardous to health. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. Chemical resistant clothing (e.g. chemical splash suit) and positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 2 - Intense or continued (but not chronic) exposure could cause temporary incapacitation or possible residual injury.
NFPA - Flammability: 1 - Must be preheated before ignition can occur.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 110.12

Conversion Factor:
Not applicable

Physical State: Solid
Melting Point: 173-174 deg C (343.4-345.2 deg F) (1,5)
Boiling Point: 285-287 deg C (545-548.6 deg F) (1,31)
Relative Density (Specific Gravity): 1.33 at 15 deg C (1,31); 1.36 at 20 deg C (32) (water = 1)
Solubility in Water: Moderately soluble (7 g/100 mL at 25 deg C) (1,5,32)
Solubility in Other Liquids: Soluble in ethanol, acetone, methyl isobutyl ketone, ethyl acetate, diethyl ether and 2-ethylhexanol; sparingly soluble in benzene and carbon tetrachloride.(1,7,31)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 0.50; 0.59 (32,40)
pH Value: Water solutions are weakly acidic.
Acidity: Very weak acid. pKa1 = 9.99 (Ka1 = 1.22 X 10(-10)) (1,31); pKa2 = 11.6 (1); pKa2 = 12.03 (Ka2 = 9.28 X 10(-13)) (31)
Vapour Density: Not applicable
Vapour Pressure: 2.4 x 10(-6) kPa (1.8 x 10(-5) mm Hg) at 25 deg C; 0.133 kPa (1 mm Hg) at 132.4 deg C (1)
Saturation Vapour Concentration: Extremely low; 0.024 ppm at 25 deg C (calculated)
Evaporation Rate: Negligible.

SECTION 10. STABILITY AND REACTIVITY

Stability:
Hydroquinone is sensitive to moist air and light, forming the more volatile 1,4-benzoquinone, which sublimes at room temperature. Dry, pure hydroquinone is very stable to oxidation. In water solution, the rate of oxidation depends on pH, occurring very rapidly even in slightly alkaline solutions (pH 7.3-7.8). Oxidation occurs slowly in neutral solution and very slowly in acidic medium.(1,2,32)

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


STRONG BASES (e.g. sodium hydroxide) - a violent reaction may occur.(5,35,37,41)
STRONG OXIDIZING AGENTS (e.g. hydrogen peroxide, nitric acid, perchlorates, persulfates) - may react vigorously or violently. Increased risk of fire and explosion.(1,5,37)
COPPER IONS - strongly catalyzes the air oxidation of hydroquinone.(1,2)

Hazardous Decomposition Products:
Reversibly oxidizable to 1,4-benzoquinone.

Conditions to Avoid:
Moist air, alkaline conditions, ultraviolet light, generation of dust, electrostatic spark, open flames, temperatures above 165 deg C, other ignition sources.

Corrosivity to Metals:
Hydroquinone is not corrosive to steel, cast iron, stainless steel, nickel and its alloys, aluminum, titanium and lead.(42) Copper and its alloys should not be used since copper ions catalyze the oxidation of hydroquinone.(1)

Stability and Reactivity Comments:
Hydroquinone is a reducing agent. Hydroquinone can be readily degraded by ultraviolet light to form 1,4-benzoquinone and 2-hydroxy-1,4-benzoquinone.(1)


SECTION 11. TOXICOLOGICAL INFORMATION

LD50 (oral, rat): 320 mg/kg (1); 320 mg/kg (fasted), 1080 mg/kg (unfasted) (20)
LD50 (oral, mouse): 245 mg/kg (21, unconfirmed)

LD50 (dermal, mouse): Greater than 3840 mg/kg (1)

Eye Irritation:

Hydroquinone is probably a mild eye irritant, based on limited information.

Immediate irritation and tearing were observed following application of powdered hydroquinone to dogs and guinea pigs.(1) Mild irritation of the inner eyelids was observed in 3/6 animals (species unreported) following application of a 2% solution. This effect had disappeared by the following day.(7) Long-term exposure can result in corneal injury. Clouding of the cornea was observed within 4 days following application of powdered hydroquinone to dogs and guinea pigs, twice daily for 9 weeks. Ulcers were observed in a few guinea pigs. All effects cleared within 3 days after treatment stopped.(1) Discolouration of the inner eyelids and corneas was observed in rabbits following application of finely powdered hydroquinone for 2-4 months. Harmful effects on the cornea were also observed.(1)

Skin Irritation:

Hydroquinone is probably a mild skin irritant, based on limited information.

Slight irritation was observed in rabbits following application of a 10% water solution for an unspecified duration. No irritation was observed following application of 0.5 to 5%.(1) Slight to severe redness due to mechanical irritation was observed in rats following application of 25 or 150 mg/kg for 24 hours.(18) Long-term skin application can result in loss of skin colour and weak to severe irritation. Weak to moderate depigmentation, sometimes with irritation, was observed in several studies following long-term dermal application of creams or ointments containing as low as 1% hydroquinone.(1,22) Moderate to severe irritation has been observed following application of 5% hydroquinone for 13 weeks.(1)

Effects of Short-Term (Acute) Exposure:

Skin Contact:
No conclusions can be drawn from a report in which reduced body weight was observed in male rats following application of 3840 mg/kg/day for 14 days (as a 95% solution in ethanol). This effect was not observed in female rats or mice of either sex. Only limited examination of the animals was conducted.(1)

Ingestion:
In acute lethality studies, oral administration has produced symptoms such as increased excitability, tremors, convulsions, shortness of breath and bluish discolouration of the skin (cyanosis).(1,2,18) Tremors, convulsions and deaths were observed in mice following oral administration of 250 or 500 mg/kg/day in corn oil for 14 days. All rats receiving 1000 mg/kg/day died.(1) Corn oil may have increased the toxicity of hydroquinone in this study. Mild kidney effects were observed in male rats following oral administration of 50 mg/kg/day for 1 week. These effects were not observed in males at lower doses nor in females at any dose.(1) Minor urinary effects were observed in rats, but not mice, following a single oral administration of 200 or 400 mg/kg. These effects often varied for different strains of rat or between males and females of the same strain.(1,18)

Effects of Long-Term (Chronic) Exposure:

Oral exposure to doses above 64 mg/kg/day for 13 weeks has produced nervous system effects in rats. Oral exposure to 50 mg/kg/day for 2 years has produced severe kidney injury in male rats.

Inhalation:
There are insufficient details available to evaluate a report of harmful blood system effects reported in rats exposed by inhalation to 10 mg/m3 intermittently for 17 weeks.(21, unconfirmed)

Ingestion:
Nervous system effects such as tremors and reduced activity were observed in rats orally exposed to 64 or 200 mg/kg/day for 13 weeks, but not at 20 mg/kg/day. Brown urine was observed in all dose groups, but there were no treatment-related kidney effects.(1,18) In another study, administration of 400 mg/kg/day in corn oil for 13 weeks was lethal to all rats and 16/20 mice. In rats, 200 mg/kg/day produced nervous system effects, decreased body weight, kidney effects and irritation of the forestomach. No effects were observed at 100 mg/kg/day or less. In mice, reduced activity was observed at 100 mg/kg/day and above. Increased liver weight was observed in all dosed groups.(1) Mild kidney effects were observed in one strain of male rat, but not in females or in another strain, following oral administration of 50 mg/kg/day for 6 weeks.(1) In a 2 year study, rats and mice were orally exposed to 0, 25 or 50 mg/kg/day or 0, 50 or 100 mg/kg/day, respectively. There were no clinical signs of toxicity. Increased liver and kidney weights, as well as kidney injury were observed in male rats at 50 mg/kg/day. Mild blood cell effects were observed in high dose females. Increased liver weights were observed in mice of both sexes and increased kidney weights in females. Liver cell changes were observed in all dosed male mice.(1,18) No conclusions can be drawn from a study in which blood system changes were observed in some male rats following oral administration of doses as low as 15 mg/kg/day for 40 days. Statistical analysis of the data was not conducted.(1,2)

Skin Sensitization:
Sensitization reactions were observed in 22 to 70% of guinea pigs in a number of studies.(1)

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has determined there is limited evidence for the carcinogenicity of hydroquinone to experimental animals.(45) The American Conference of Governmental Industrial Hygienists has concluded that hydroquinone is an A3 (animal carcinogen).
In a US National Toxicology Program (NTP) study, oral administration of hydroquinone produced some evidence of carcinogenic activity in male rats (kidney adenomas), female rats (leukemia), and female mice (liver neoplasms).(23,24) Benign kidney tumours were also observed in male rats in another study following oral administration of hydroquinone.(1,25) One reviewer has concluded that the leukemia observed in female mice was within historical control values and that no firm conclusions regarding carcinogenicity can be drawn based on the liver neoplasms observed in female mice. The kidney tumours observed in male rats may occur only in the presence of other harmful effects on the kidney.(25) It is not possible to draw firm conclusion from reports of other carcinogenic effects because results have not been consistent, a dose-response relationship was often lacking, results were within the historical range for controls and/or the tumours were often observed only in one sex.(25) Hydroquinone has shown no tumour promoting activity in most studies.(45)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Harmful effects have not been observed in the absence of maternal toxicity. Embryotoxic and fetotoxic effects have been observed in rats and rabbits following oral administration of doses which have also produced maternal toxicity. No studies have shown teratogenicity.
Two studies have shown fetotoxic (reduced weight) and/or embryotoxic (resorptions) effects in rats and rabbits following oral administration of 200 or 300 mg/kg/day during pregnancy. Maternal toxicity was observed. Harmful effects were not observed at lower doses. Teratogenicity was not observed.(1,26) Embryotoxic effects have also been observed in other oral studies. However, these studies are not relevant because the dose used was very high in one study (27) and the other was poorly reported and conducted (28). Teratogenic, embryotoxic and/or fetotoxic effects were not observed in other studies following ingestion or skin application of hydroquinone. In some of these studies, harmful effects on the mothers were observed.(1,7)

Reproductive Toxicity:
Harmful effects on fertility were not observed in male or female rats following oral administration of up to 150 mg/kg/day in 2 two- generation studies.(1,29) Similar results have been obtained in other studies.(1,20) Negative results were also obtained in a dominant lethal assay following oral administration of 30-300 mg/kg/day to male rats for 10 weeks prior to mating.(1) No harmful testicular or epididymal effects were observed in rats and mice following oral administration of up to 400 mg/kg/day in corn oil for 13 weeks or up to 50 mg/kg/day in rats or 100/mg/kg/day in mice for 2 years.(1) No conclusions can be drawn from an oral exposure study which observed harmful effects on the fertility cycle of female rats because significant other toxic effects were also observed.(1,2)

Mutagenicity:
It is not possible to conclude that hydroquinone is mutagenic based on the available information.
Positive results (micronuclei induction) were obtained in the bone marrow cells of mice exposed orally, but cell toxicity was evident.(46) Positive results (chromosomal aberrations, micronuclei) have been obtained in the germ and somatic cells of mice exposed by injection, a route of exposure not relevant to occupational exposures.(1,25,30,45) Negative results have been obtained in some other studies using live animals.(1)
Positive results have been obtained tests using cultured mammalian cells including human cells, with and/or without metabolic activation.(1) Mainly negative and a few positive results have been obtained in many tests using bacteria, both with and without metabolic activation.(1,25) Positive results have been obtained in yeast.(45)
Negative results were obtained in a sex-linked recessive lethal mutation study using fruit flies.(45)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) International Programme for Chemical Safety (IPCS). Hydroquinone. Environmental health criteria; 157. World Health Organization, 1994
(2) Criteria for a recommended standard: occupational exposure to hydroquinone. National Institute for Occupational Safety and Health, Apr. 1978
(3) Oglesby, F.L., et al. Quinone vapor and their harmful effects: II. Plant exposures associated with eye injuries. Journal of Industrial Hygiene and Toxicology. Vol. 29, no. 2 (Mar. 1947). p. 74-84
(4) Barber, E.D., et al. The percutaneous absorption of hydroquinone (HQ) through rat and human skin in vitro. Toxicology Letters. Vol. 80, nos. 1-3 (Oct. 1995). p. 167-172
(5) International Programme on Chemical Safety (IPCS). Hydroquinone: health and safety guide. Health and safety guide no. 101. World Health Organization, 1996
(6) Hooper, R.R., et al. Hydroquinone poisoning aboard a navy ship. Abstract. Morbidity and Mortality Weekly Report. Vol. 27, no. 28 (July 14, 1978). p. 237-238
(7) Stenius, U. Hydroquinone. In: Criteria documents from the Nordic Expert Group 1989. Edited by G. Heimburber, et al. Arbete och Halsa. Vol 37 (1989). p. 79-113
(8) Pifer, J.W., et al. Mortality study of employees engaged in the manufacture and use of hydroquinone. International Archives of Occupational and Environmental Health. Vol. 67, no. 4 (Aug. 1995). p. 267-280
(9) Fitzpatrick, T.B., et al. Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo. Archives of Dermatology. Vol. 93, no. 5 (May 1966). p. 589-600
(10) Liden, C. Occupational dermatoses at a film laboratory: follow-up after modernization. Contact Dermatitis. Vol. 20, no. 3 (1989). p. 191-200
(11) Grant, W. M., et al. Hydroquinone. In: Toxicology of the eye. 4th ed. Charles C. Thomas, 1993. p. 801-805
(12) Anderson, B. Corneal and conjunctival pigmentation among workers engaged in manufacture of hydroquinone. Archives of Ophthalmology. Vol. 38 (Dec. 1947). p. 812-826
(13) Sterner, J.H., et al. Quinone vapors and their harmful effect: I. Corneal and conjunctival injury. Journal of Industrial Hygiene and Toxicology. Vol. 29, no. 2 (Mar. 1947). p. 60-73
(14) Nowak, A.K., et al. Darkroom hepatitis after exposure to hydroquinone. Lancet. Vol. 345, no. 8958 (May 6, 1995). p. 1187
(15) International Agency for Research on Cancer. Dihydroxybenzenes. In: Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 15. Some fumigants, the herbicides 2,4-D and 2,4,5-T, chlorinated dibenzodioxins and miscellaneous industrial chemicals. World Health Organization, Aug. 1977. p. 155-175
(16) International Agency for Research on Cancer. Results and conclusions. In: IARC monographs on the evaluation of carcinogenic risks to humans. Suppl. 7. Overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to 42. World Health Organization, 1987. p. 64
(17) Nielsen, H., et al. Malignant melanoma among lithographers. Scandinavian Journal of Work, Environment and Health. Vol. 22, no. 2 (Apr. 1996). p. 108-111
(18) Zondlo, M.M. Addendum to the final report on the safety assessment of hydroquinone. Journal of the American College of Toxicology. Vol. 13, no. 3 (June 1994). p. 167-230
(19) Hydroquinone. In: Documentation of the threshold limit values and biological exposure indices. 6th ed. American Conference of Governmental Industrial Hygienists, 1991
(20) Carlson, A.J., et al. Toxicity studies on hydroquinone. Proceedings of the Society for Experimental Biology and Medicine. Vol. 84 (1953). p. 684-688
(21) RTECS record for hydroquinone. Last updated: 1997-10
(22) Jimbow, K., et al. Mechanism of depigmentation by hydroquinone. Journal of Investigative Dermatology. Vol. 62, no. 4 (Apr. 1974). p. 436-449
(23) Kari, F.W. NTP technical report on the toxicology and carcinogenesis studies of hydroquinone (CAS no. 123-31-9) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program, U.S. Department of Health and Human Services, Oct. 1989
(24) Kari, F.W., et al. Toxicity and carcinogenicity of hydroquinone in F344/N rats and B6C3F1 mice. Food and Chemical Toxicology. Vol. 31, no. 9 (Sept. 1992). p. 737-747
(25) Whysner, J., et al. Analysis of studies related to tumorigenicity induced by hydroquinone. Regulatory Toxicology and Pharmacology. Vol. 21, no. 1 (Feb. 1995). p. 158-176
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1998-05-27

Revision Indicators:
TLV comments 1998-08-01
Toxicological info 1999-12-01
Carcinogenicity 1999-12-01
Mutagenicity 1999-12-01
WHMIS (proposed class) 1999-12-01
WHMIS (detailed class) 1999-12-01
WHMIS (effects) 1999-12-01
Emergency overview 1999-12-01
Handling 1999-12-01
EU Class 2000-04-01
EU Risk 2000-04-01
EU Safety 2000-04-01
EU risks 2002-02-26
WHMIS disclosure list 2003-07-09
PEL-TWA final 2003-12-19
PEL transitional comments 2003-12-19
Resistance of materials for PPE 2004-04-06
Bibliography 2005-05-19
TLV-TWA 2006-02-15
TLV comments 2006-02-15
TLV definitions 2006-02-15
TLV proposed changes 2006-02-15
Conversion factor 2006-10-05
Vapour density 2006-10-05
WHMIS detailed classification 2006-10-05
Emergency overview 2006-10-05
UN/NA No 2007-01-10
US transport 2007-01-10



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