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SIDS INITIAL ASSESSMENT PROFILE

CAS No. 108-95-2 

Chemical Name Phenol 

Structural Formula 

OH

SUMMARY CONCLUSIONS OF THE SIAR 

Human Health 

Phenol is well absorbed via gastrointestinal and respiratory tract and the dermal route in animals and man. Concerning 

the oral route a high absorption was measured in rats, sheep and pigs with 90, 85, and 84% of the orally administered 

phenol dose of 25 mg/kg bw after 8 h. Volunteers exposed to phenol concentrations of 6-20 mg/m3 via inhalation 

absorbed 60 to 88% of the substance. After dermal application of phenol to rats about 80% of the applied dose was 

absorbed. Distribution of phenol in body tissues occurs rapidly. Phenol is metabolized to sulfate and glucuronide 

conjugates. Excretion via urine is the main elimination pathway of phenol metabolites in man and animals for the 

different exposure routes. The ratio of sulfate/glucuronide conjugates excreted in urine is dose-dependent with a 

capacity-limited sulfatation at high dosages in rats and mice. Cats showed a poor glucuronidation of phenol, only 

conjugation with sulfate occurred. Small amounts of conjugated hydroquinone were only detected in the metabolic 

profiles for man and rats. Metabolism predominantly occurs in liver, gut and kidneys. 

Phenol shows acute toxicity by the oral, dermal and inhalation route of application. Oral LD50 values of 340 mg/kg 

bw are reported on rats, of about 300 mg/kg bw on mice, and of less than 620 mg/kg bw on rabbits. A dermal LD50 

value of 660-707 mg/kg bw was determined for female rats. LC50 values are not available, however, rats are reported 

to tolerate phenol concentrations as high as 900 mg/m3 for 8 hours, resulting in ocular and nasal irritation, loss of coordination, tremors, and prostration. 

Acute oral toxicity of phenol in humans leading to death is reported for doses as low as 140-290 mg/kg bw. 

Absorption from spilling phenolic solutions on the skin of humans seems to be very rapid, and death resulted from 

collapse within 30 minutes to several hours. Death has resulted from absorption of phenol through a skin area of 64 

inch2, too. Signs and symptoms of acute toxicity of phenol in experimental animals and humans are similar regardless 

of the route of administration. 

Eye irritation in rabbits caused by a 5% aqueous phenolic solution was irreversible after an observation period of 7 

days. Thus, local irritation caused by phenolic solutions cannot be assessed properly. Initial skin contact of humans 

with phenol produces a white wrinkled discoloration with no experience of pain due to the local anaesthetic properties 

of phenol. Phenol causes severe chemical burns, occasionally skin necrosis is seen with diluted solutions (1%). 

Phenol did not cause any signs of skin sensitization in tests with guinea pigs (modified Buehler Test) and mice 
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(Mouse Ear Swelling Assay), and there is no evidence of allergic contact dermatitis in humans. 

A 28-day administration of phenol in the drinking water (4.7, 19.5 and 95.2 mg/l) induced anaemia in CD-1 mice at 

concentrations of 19.5 mg/l (6.2 mg/kg bw/d). Furthermore, it was shown to induce T- and B-cell suppressive effects 

(reduced lymphocyte proliferation response to mitogens, antibody levels and T-cell dependent humoral immunity) in 

mice at low dosages (6.2 mg/kg bw and above). A significantly dose-dependent reduction of erythrocyte numbers by 

32% was already seen at the lowest dose of 4.7 mg/l (1.8 mg/kg bw/d, LOAEL). Rats exposed to phenol containing 

drinking water did not show any alteration of the T-cell dependent humoral response up to 5000 ppm (301 mg/kg 

bw/d). 

In the 103-weeks cancer NIH studies (1980), F344 rats and B6C3F1 mice were administered drinking water 

containing 2500 or 5000 ppm phenol (equivalent to an assumed phenol uptake of 200 and 450 mg/kg bw/d for rats 

and 281 and 375 mg/kg bw/d for mice) for 103 weeks. Treated animals showed reduced body weights (rats at high 

dose, mice at both doses) and reduced water consumption (both species and sexes at both doses). No other relevant 

toxic effect was seen related to non-neoplastic lesions. Because the reduction of body weight gain was attributed to 

the reduced water consumption, the NOAEL from this study is 450 mg/kg bw/d for rat and 375 mg/kg bw/d for the 

mouse, respectively. Haematology parameters were not examined in these studies. 

In a study on potential neurotoxicity of phenol male and female Sprague-Dawley rats were treated for 13 weeks via 

drinking water with phenol concentrations of 200, 1000 or 5000 ppm, respectively, corresponding to an average 

intake of 18, 83 and 308 mg/kg bw/d for males and 0, 25, 107 and 360 mg/kg bw/d for females. The Functional 

Observation Battery evaluation did not reveal any findings of neurotoxicological significance following qualitative or 

quantitative measurements throughout treatment or following recovery except a significant decrease in body 

temperature noted for males in the 1000 and 5000 ppm groups at the week 13. The motor activity test indicated a 

significant reduction in total group mean activity counts at the week 4 and 8 for the 5000 ppm females and for females 

of the 1000 and 5000 ppm group at week 17 during recovery. At week 13 total mean activity counts were significantly 

higher in 1000 and 5000 ppm females. Thus, the NOAEL for neurotoxicity on rats was 200 ppm (18 mg/kg bw/d for 

males, 25 mg/kg bw/d for females). Dysfunctions of the nervous system including tremor, convulsions, loss of coordination, paralysis, reduced motor and spontaneous activity, and reduced body temperature have been reported in 

other studies. 

Specific effects of phenol on the respiratory tract were investigated in a 14 day-inhalation study in F344 rats with a 

study design similar to OECD TG 412 (nose-only exposure for 10 exposures, 5 d/week, 6 hours/d). No adverse effects 

were seen at phenol concentrations up to 25 ppm in the respiratory tract or in any other organ system (local and 

systemic NOAEC of 96 mg/m3). This value is used in the risk characterisation as NOAEC for local effects after 

inhalation. 

Prolonged dermal exposure of rabbits to phenol induced epidermal hyperkeratosis and ulceration. As dermal NOAEL 

for systemic effects the dose of 1.18% (130 mg/kg bw/d) was derived from the 18-day rabbit study, whereas the 

NOAEL for local effects was 2.37% (260 mg/kg bw/d). 

Other limited repeated dose studies reported unscheduled deaths after inhalation (100 - 200 mg/m3, hamster), dermal 

exposure (783 mg/kg bw/d, rabbit) or gavage (120 mg/kg bw/d, rat) to phenol, but no treatment-related mortalities 

have been seen after long-term exposure of phenol within the drinking water at dosages up to 450 mg/kg bw/d in rats 

and 375 mg/kg bw/d in mice. In some studies, mortalities were associated with growth retardation or respiratory 

distress. Liver damage has also been observed in rats repeatedly exposed to phenol by inhalation and the oral route 

(enlarged liver, elevated levels of liver enzymes and liver cell degeneration). Necrosis of renal tubules and papillary 

hemorrhage have been reported in rats after repeated oral administration. 

Limited data are available on chronic effects of phenol in humans from oral, dermal or inhalation exposure indicating 

reduced spontaneous activity, muscle weakness, pain and disordered cognitive capacities. In phenol-exposed workers 

(mean exposure duration 13.5 ± 6.55 years) elevated activities for serum transaminases (especially ALAT) and 

increased clotting time were observed at a time weighted average concentration of 21 mg/m3 indicating hepatotoxicity 

after chronic inhalation (LOAEC for systemic effects). 
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Phenol did not induce gene mutations in the vast majority of bacterial tests similar to OECD TG 471. In mammalian 

cell cultures positive effects were found for chromosomal aberrations, micronuclei, and gene mutations (hprt locus, 

Na+/K+ locus) in mouse lymphoma assays and in several indicator tests (SCE, UDS, DNA strand breaks and DNA 

adducts). A test for induction of aneuploidy was negative. In vivo, negative results were found in rodents for 

chromosomal aberrations, DNA strand breaks and DNA adducts. In vivo micronucleus tests showed negative and 

weakly positive results. The frequency of micronuclei is extremely low even in doses which correspond to the LD50. 

The induction of micronuclei at high doses may be based on an indirect mode-of-action (hypothermia). Drosophila 

tests were negative. 

In 103-weeks cancer studies on F344 rats and B6C3F1mice with oral administration (drinking water, 2500 and 5000 

ppm,  200 and 450 mg/kg bw/d for rats and 281 and 375 mg/kg bw/d for mice, respectively) phenol was not 

carcinogenic for both species and sexes. A medium-term study in a transgenic mouse model did not give any 

indication on treatment-related proliferative responses. Phenol was shown to act as a promoter in a skin cancer 

bioassays in mice. A weak carcinogenic effect was observed after long-term skin application of a 10% solution of 

phenol in benzene (without initiation), but was considered less relevant because the test solution was strongly 

irritative and it contained the carcinogen benzene. Some concern which may be derived from weakly positive in vivo 

mutagenicity data and from the phenol metabolite hydroquinone suspected as a carcinogen is considered to be of 

minor significance, as the long term studies revealed no relevant indication for carcinogenicity. 

There are no epidemiologic data revealing an association of phenol exposure to increased tumor rates in humans. No 

firm conclusion could be drawn from a case-control study on respiratory cancer of workers exposed to phenol. 

Phenol was investigated for impairment of reproductive performance and fertility in a two-generation (drinking water) 

reproductive toxicity study in rats according to OPPTS 870.3700 resp. OECD TG 416. No adverse effects on 

reproductive capability and fertility were revealed for either sex across two generations up to and including the 

highest dosages tested (5000 ppm, according to 300 (males) and 320 (females) mg/kg bw/d). At this dose reduced 

water intake, decreased body weight and body weight gain including organ weight impairment were observed in 

animals of the P0 and F1 generation. No effects on sperm parameters or on estrous cyclicity were revealed. No 

substance specific developmental toxicity was revealed for phenol in studies on mice and rats with oral (gavage) 

administration. From the overall assessment of all available data a NOAEL/developmental toxicity of 93 mg/kg bw/d 

is derived which is based on the observations upon offspring performance and development in the rat two-generation 

study. 

Environment 

Phenol is a solid with a boiling point of about 182 °C and a melting point of about 41 °C. Its density is 1.132 g/cm3 

at 25 °C. It has a water solubility of 84 g/l at 20 °C, a vapor pressure of 0.2 hPa (at 20 °C) and a measured log Kow 

of 1.47. With a Henry’s law constant of 0.022 Pa.m3.mol-1 phenol is only slightly volatile from aqueous solutions. 

Based on the results of standard biodegradation tests, phenol is readily biodegradable (OECD 301C: 85 % after 14 

d). From available investigations on the biodegradation of phenol in surface waters a rate constant of 0.05 d-1 was 

determined. In soils phenol is biodegraded with an experimentally determined rate constant of 0.1 d-1. 

Hydrolysis under environmental conditions is not expected due to the chemical structure of phenol. 

In the atmosphere phenol reacts with photochemically formed OH radicals with an estimated half-life of 14 hours. 

Products of this degradation are catechol and ring cleavage products. In addition, degradation through NO3 radicals 

may also play an important role with a half-life of approx. 44 min. A half-life of 42 min is calculated for the 

degradation of phenol in the atmosphere considering both processes. 

According to a fugacity model (Mackay level I) the hydrosphere is identified as target compartment for phenol 

(98.8 %). Based on the measured log Kow of 1.47, the Koc value is calculated to 82.8 l/kg. This value indicates a 

low potential for geoaccumulation. From the available studies on bioaccumulation it can be stated that phenol has a 
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low bioaccumulation potential (Brachydanio rerio: BCF = 17.5). 

Short- and long-term tests are available for fish, invertebrates and algae. The lowest effects values from the shortterm tests are: Ocorhynchus mykiss: 96h-LC50 = 5.02 mg/l; Ceriodaphnia dubia: 48h-LC50 = 3.1 mg/l, Selenastrum 

capricornutum: 96h-ErC50 = 61.1 mg/l, Skeletonema costatum: 120h-EC50 = 49.6 mg/l, 120h-NOEC = 13 mg/l. In 

long-term tests with fish the lowest valid effect value was found for Cirrhina mrigala: 60d-NOEC = 77 μg/l (survival 

and growth). In a 16d test with Daphnia magna an EC10 of 0.46 mg/l was found for gowth reduction as test endpoint. 

The PNECaqua is derived from the lowest available NOEC using an assessment factor of 10, resulting in a PNEC of 

7.7 μg/l. In a nitrification inhibition test with Nitrosomonas a 24h-EC50 of 21 mg/l was found. 

For the terrestrial compartment short-term tests with plants and earthworms are available. The following results were 

obtained: Lactuca sativa: 14d-EC50 = 79 - 168 mg/kg dw; Eisenia fetida: 14d-LC50 = 401 mg/kg dw. 

Exposure 

The total amount of phenol produced in the EU is about 1,820,000 t/a. In addition, a quantity of about 113,000 t/a is 

imported into the EU annually. 290,000 t/a are exported to non-EU countries. The quantity used in the EU is 

therefore approx. 1,643,000 t/a. Data about global production volumes are not available. 

Phenol is mainly used as an intermediate in organic synthesis. Phenol essentially serves as a raw material for the 

production of Bisphenol A, phenol resins, alkylphenols, caprolactam, salicylic acid, nitrophenols, diphenyl ethers, 

halogen phenols and other chemicals. A small, non-quantifiable part serves as a component in cosmetics and medical 

preparations. 

According to information from the Nordic product register phenol is contained in a large number of products. The 

following product types are described: intermediate, adhesive, binder, impregnating agent, paints, lacquers and 

varnishes, solvents, flooring, hardeners and insulating materials. The Swedish product register (2000) gives the 

information that there are 5 consumer products that contain phenol. 3 products have a phenol content of max. 0.1 %, 

2 products (hardeners for adhesives) have a phenol content of 1 – 5 %. It is not clear from the product registers 

which quantity of the substance is used as an intermediate in the manufacture of products such as phenol resins and 

binders and how much remain unchanged in the final product. 

Phenol is released from a number of man-made sources. The primary sources of environmental phenol are 

automobile exhaust (direct emission and photochemical degradation of benzene), human and animal metabolism and 

different combustion processes. From industrial sources, it enters the environment from production and processing 

operations. Releases also occur due to the waste water from cooking plants and low-temperature carbonisation plants 

using hard coal and brown coal, from refineries, from pulp manufacture and landfill leachate. Phenol may enter the 

soil as a result of the spreading of sewage sludge and liquid manure from livestock farming. 

RECOMMENDATION AND RATIONALE FOR THE RECOMMENDATION AND NATURE 

OF FURTHER WORK RECOMMENDED 

Human Health: The chemical is a candidate for further work. The chemical possesses properties indicating a hazard 

for human health. Due to the use pattern of the substance, member countries are invited to perform an exposure 

assessment, and if necessary a risk assessment for human health. 

Note: A risk assessment performed in the European Union in the context of the EU Existing Substances Regulation 

reveals concern for several toxicological endpoints. Regarding systemic repeated dose toxicity and possible irritation, 

risk reduction measures are considered to be necessary for dermal exposure of consumers via cosmetics (soap, 

shampoo as well as cleaners). Concern is expressed for repeated inhalation exposure due to application of floor 

waxes. For workers additional risk reduction measures are necessary for inhalative and dermal exposure in several 

scenarios. Concern is expressed for corrosivity following skin contact and contact to the eyes, acute toxicity, and 
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This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in this 

document are intended to be mutually supportive, and should be understood and interpreted together.

systemic toxicity following repeated dermal exposure. Special emphasis should be given by risk managers to all 

dermal exposure scenarios, because it is known, that sensation of pain due to local exposure to phenol may be 

diminished possibly leading to less awareness and thus higher degrees of local damage. 

Environment: The chemical is currently of low priority for further work. The chemical possesses properties 

indicating a hazard for the environment. Although these hazards do not warrant further work as they are related to 

acute toxicity which may become evident only at very high exposure concentrations, they should nevertheless be 

noted by chemical safety professionals and users. 

Note: A risk assessment for phenol was prepared in the EU in the context of the EU Regulation 793/93. No concern 

was identified for the environmental compartments from production and use of phenol. A concern for industrial 

wastewater treatment plants was identified for 8 out of 32 sites. For all these sites the wwtp concentration is based on 

default values and could possibly be lowered by site-specific and traceable exposure data. However, it was not 

possible to get this information with reasonable effort and time expenditure anda risk reduction strategy is therefore 

currently under development in the EU. In addition, some unintentional releases of phenol were identified in the risk 

assessment that may result in a risk to the aquatic compartment. However, based on the insufficient data basis, no 

clear conclusion could be drawn. This applies to: 

direct discharges of phenol as a product of human metabolism without purification of the municipal waste 

water in a biological treatment plant. 

the coking, gasification and liquefaction of coal, refineries and pulp manufacture. 

exposure to the aquatic and terrestrial environment from landfills without landfill leachate collecting system 

the terrestrial compartment as a result of the spreading of liquid manure from livestock farming