OECD SIDS

m- / p-CRESOLFOREOWRD

INTRODUCTION

M/P-CRESOL CATEGORY
m/p-Cresol CAS N°:15831-10-4
m-Cresol
CAS No: 108-39-4
p-Cresol
CAS No: 106-44-5

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m- / p-CRESOLSIDS Initial Assessment Report
For
SIAM 16
Paris, France, 27 – 30 May 2003
1. Category Name:

m/p-Cresol

2. CAS Numbers:m/p-Cresol Category:m-Cresol
CAS No: 108-39-4
p-Cresol
CAS No: 106-44-5
m/p-Cresol CAS No: 15831-10-4
Germany
Contact Point:
BMU (Bundesministerium für Umwelt, Naturschutz undReaktorsicherheit)
Contact person:
Prof. Dr. Ulrich Schlottmann
Postfach 12 06 29
D- 53048 Bonn-Bad Godesberg

3. Sponsor Country:

4. Shared Partnership with:
5. Roles/Responsibilities of
the Partners:•

Name of industry sponsor/consortium•

Process used

Bayer AG, Germany
Contact person:
Dr. Burkhardt Stock
D-51368 Leverkusen
Gebäude 9115
see below

6. Sponsorship History•

How was the chemical or
category brought into theOECD HPV Chemicals
Programme ?

7. Review Process Prior to
the SIAM:

8. Quality check process:9. Date of Submission:

last literature search (update):
01.06.2002 (Human Health): databases medline, toxline; search
profile CAS-No. and special search terms
15.05.2002 (Ecotoxicology): databases CA, biosis; search profile
CAS-No. and special search terms
As basis for the SIDS-Report the IUCLID was used. All data
have been checked and validated by BUA.
19 February 2003

10. Date of last Update:
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11. Comments:

m- / p-CRESOLOECD/ICCA - The BUA* Peer Review Process
Qualified BUA personnel (toxicologists, ecotoxicologists)
perform a quality control on the full SIDS dossier submitted byindustry. This quality control process follows internal BUA
guidelines/instructions for the OECD/ICCA peer review process
and includes:− a full (or update) literature search to verify completenessof data provided by industry in the IUCLID/HEDSET− Review of data and assessment of the quality of data
− Review of data evaluation− Check of adequacy of selection process for key studies forOECD endpoints, and, where relevant, for non-OECD
endpoints by checking original reports/publications− Review of key study description according robust
summaries requirements; completeness and correctness ischeckedagainstoriginal
reports/publications(if original reports are missing: reliability (4), i.e.
reliability not assignable)− Review of validity of structure-activity relationships− Review of full SIDS dossier (including SIAR, SIAP andproposal for conclusion and recommendation for further
work)− In case of data gaps, review of testing plan or rationale for
not testing* BUA (GDCh-Beratergremium für Altstoffe): Advisory Committee on Existing Chemicals of the Association ofGerman Chemists (GDCh)UNEP PUBLICATIONS

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OECD SIDS

m- / p-CRESOLSIDS INITIAL ASSESSMENT PROFILECAS No.

108-39-4

106-44-5

15831-10-4

Chemical Name

m-Cresolp-Cresolm/p-Cresol mixtures

OH

Structural Formula

OH

CH3
CH3
m-Cresolp-Cresol

SUMMARY CONCLUSIONS OF THE SIAR
Category Rationale
m-Cresol, p-cresol and mixtures of both isomers can be considered as a single category because of their similarity
in physico-chemical properties, distribution between environmental compartments, degradation, ecotoxicity, andtoxicology.
Human Healthm-Cresol, p-cresol and m/p-cresol mixtures are absorbed across the respiratory and gastrointestinal tracts and throughthe skin, and are distributed throughout the body. The primary metabolic pathway for all cresol isomers is
conjugation with glucuronic acid and inorganic sulfates. All isomers are mainly eliminated by renal excretion in formof conjugates. For p-cresol, oxidation to a reactive quinone methide intermediate was found in rat liver in vitro. The
oral LD50 of undiluted m-cresol in rats was 242 mg/kg bw; and the LD50 of undiluted p-cresol was 207 mg/kg bw.
Thus, it can be assumed that the LD50 of m/p-cresol mixtures is slightly above 200 mg/kg bw. Clinical signs
included hypoactivity, salivation, tremors, and convulsions. No mortality nor clinical signs of toxicity were seen
following exposure to saturated vapour concentration of either m-cresol or p-cresol. Inhalation of aerosols may
however cause death, and mean lethal concentrations in rats were reported to be 29 mg/m³ for p-cresol and 58 mg/m³
for m-cresol. Clinical signs included irritation of mucous membranes, excitation and convulsions. Haematuria wasreported at very high concentrations. Following dermal application in rabbits the LD50 of undiluted m-cresol was
2050 mg/kg bw and the LD50 of p-cresol was 300 mg/kg bw. It can be assumed that the LD50 of m/p-cresol
mixtures is between 300 and 2000 mg/kg bw.
m-Cresol, p-cresol and m/p-cresol mixtures are corrosive to the skin and may cause serious damage to the eyes.
There is no indication of a sensitizing effect of p-cresol and m/p-cresol from a limited guinea pig study and a limited
human study. No sensitization test was available for m-cresol. In a survey article hypersensitivity reactions of someindividuals to cresol (isomer unspecified) have been mentioned.
In 28-day and 13-week feeding studies, m-cresol, p-cresol and m/p-cresol (60:40) had a very similar pattern of
toxicity in rats and mice with minimal effect levels of 1000 – 3000 ppm in the diet for increases in liver weight (rat,mouse) and kidney weight (mouse, p-cresol). No increase in relative kidney weight was found for m-cresol. Atrophy
and regenerative changes in the nasal epithelia and forestomach were seen after exposure to p-cresol and m/p-cresol,
presumably as direct result of the irritant effects of the chemicals. The no observed adverse effect levels (NOAELs)
for m-cresol, p-cresol and m/p-cresol were generally ≥ 50 mg/kg bw/day in rats and mice.
In vitro, m-cresol and p-cresol did not induce gene mutations in bacterial and mammalian cell systems and m/p-cresol
mixture did not induce gene mutations in bacteria. m-Cresol was negative for clastogenic activity in vitro, and invivo. p-Cresol was clastogenic in vitro, but has not been adequately tested in somatic cells in vivo. p-Cresol was,however, negative for dominant lethal mutations in germ cells in male mice at clearly toxic exposure levels. A 60:40
m/p-cresol mixture did not increase the frequency of micronucleated erythrocytes in the peripheral blood erythrocytes

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of mice. In vitro, it is possible that m- and p-cresol and m/p-cresol mixture have the potential to interact with DNA
either directly or indirectly via metabolites.
As for o-cresol, there are no adequate data available to assess the carcinogenic potential of m-cresol, p-cresol or m/pcresol mixtures. From tumour promotion studies in mice there are some indications that cresols may act as promoters.
Currently, the U.S. National Cancer Institute is performing a carcinogenicity feeding study on mice and rats withcresols (mixture of ortho-, meta- and para-) within the National Toxicological Program (NTP).
Despite general toxicity (hypoactivity, ataxia, twitches, tremors, prostration, urine stains, audible respiration, perioral
wetness) fertility was not affected by treatment with m-cresol or p-cresol (NOAEL, rat: 450 mg/kg bw/day). The
NOAELs for general toxicity were determined as 30 mg/kg bw/day. Fertility effects including a 20% reduction inpup survival as well as reductions in the weights of male reproductive organs were found following treatment of micewith m/p-cresol mixture in a continuous breeding study at systemically toxic dose levels (reduced food consumption
and reduced body weights, increases in liver and kidney weights) (NOAEL, fertility and general toxicity: 0.25 % in
feed (ca. 375 mg/kg bw/day).
In developmental toxicity studies with m-cresol in rats and rabbits, no toxic effects on the developing organism could
be found despite of the toxic effects on the dams as evidenced by hypoactivity, ataxia, tremor, twitches, prone
positioning, audible respiration, perioral wetness, and a reduction in food consumption in rats, and audible
respiration, and ocular discharge in rabbits (NOAELs: 175 mg/kg bw (maternal toxicity) and 450 mg/kg bw(developmental toxicity) for rats, and 5 mg/kg bw (maternal toxicity) and 100 mg/kg bw (developmental toxicity) for
rabbits, respectively. p-Cresol caused fetotoxicity (delayed ossification, decreased fetal body weight) at maternally
toxic dose levels in rats, but not in rabbits (NOAEL, rat, maternal toxicity, developmental toxicty: 175 mg/kg
bw/day). Based on the available data, it can be assumed that m/p-cresol mixtures may have the potential to induce
fetotoxicity in the presence of maternal toxicity.
In humans, the accidental oral uptake of cresols can induced irritation of mouth and throat, abdominal pains,vomiting, haemolytic anemia, increased heart rate, liver and kidney damage, headaches, facial paralysis, drowsiness,
cramps, coma and death. Skin contact with cresols can result in corrosion, skin depigmentation, effects on the
nervous system, liver and kidneys, gastrointestinal bleeding, and can cause human fatalities.
There are some case reports about tumour development in connection with probable exposure against cresol isomers.
Since co-exposures to other substances cannot be excluded, no conclusion on a carcinogenic potential can be deduced
from these case reports.
Environmentm-Cresol, p-cresol and m/p-cresol mixtures have a melting point of ca. 10 - 35°C, a water solubility in the range of
21.5 - 24.4 g/l (25°C), a density of about 1.03 g/cm³ (20°C), and a vapour pressure of 0.147 Pa (25°C). The
experimentally determined log Kow are in the range of 1.94 - 1.96.
According to a Mackay Level I model calculation, the main target compartment for m-cresol and p-cresol is thehydrosphere (96.3%). In the atmosphere m-cresol and p-cresol are indirectly photodegradable by hydroxyl radicals
with half–lives t1/2 = 6.0 – 8.2 hours (OH concentration 5⋅10 5 molecules/cm³). The measured Henrys’ law constantsof 0.09 Pa⋅m³/mol (m-cresol) and 0.1 Pa⋅m³/mol (p-cresol) indicate slow volatilization from surface waters.
Adsorption onto soils and sediments are low, according to experimentally determined Koc values of 34.58 for mcresol and 48.66 for p-cresol.
With regard to the chemical structure m-cresol and p-cresol are not expected to hydrolyse under environmental
conditions. Aerobic biodegradation is considered to be the major removal mechanism in the hydrosphere, leading tocomplete mineralization. From the available test results, m-cresol and p-cresol can be considered as being readily
biodegradable under aerobic conditions. In surface waters and sediments half-lives in the range of some hours to afew days are expected. Photolytical degradation in surface waters as well as anaerobic degradation in lower
sediment layers are expected to be of minor importance.
For m-cresol, a BCF of 20 was obtained in a laboratory tests on fish, indicating a low bioaccumulation potential.
Because of the similarity of the log Kow the accumulation potential of m-cresol, p-cresol and m/p-cresol mixtures isassumed to be low.
For the acute toxicity of cresols on aquatic species experimental results with m-cresol and p-cresol from tests with

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fish, daphnids and algae are available. Long-term tests were conducted for p-cresol with fish, algae andinvertebrates. Effect values with the same tested species indicate toxicity in the same order of magnitude, with pcresol being slightly more toxic. Therefore, it is assumed that the long-term toxicity of both isomers is similar as
well. No ecotoxicity tests are available for the isomeric mixture m/p-cresol. However, it is expected that the toxicityof the isomeric mixture is covered by the data for m- and p-cresol.
In acute toxicity tests the following results were obtained with either m-or p-cresol:
fish (15 species):
invertebrates (4 species):
algae (2 species):

48 - 96 h LC50 = 4.4 - 57.5mg/l;
24 - 48 h LC50 = 4.9 - > 99.5 mg/l;
48 – 72 h EC50 = 21 - 127mg/l.

Results from long-term tests for p-cresol are available for fish, invertebrates and algae, the most sensitive species
being Pimephales promelas (NOEC = 1.35 mg/l), Daphnia magna (NOEC = 1 mg/l) and Scenedesmus subspicatus(ErC10 = 4.6 mg/l, EbC10 = 2.3 mg/l). Applying an assessment factor of 10 to the lower value, a Predicted No
Effect Concentration (PNEC) for the aquatic compartment of 0.1 mg/l is determined for m- and p- cresol and theisomeric mixture m/p-cresol.
Exposure
Cresols (mixed isomers) are widespread in nature, occurring, for instance, in many plants, petroleum, coal tar, crude
oil and volcanic actions. They are emitted from municipal incinerators, during coal and wood combustion, withvehicle exhaust, from oil refineries and cigarette smoke. Cresols are also products of the photooxidation of toluene.
p-Cresol is an endogenous metabolite of the amino acid tyrosine in humans and warm-blooded animals.
The world production capacity amounts of about 28,500 tonnes for m-, 59,500 tonnes for p-, and 128,000 tonnes forthe m/p-cresol isomeric mixture. The largest part of cresols are used as intermediates in chemical processes for the
production of e.g. antioxidants, arylphosphates, synthetic Vitamin E and pesticides. m/p-Cresol isomeric mixture isused as a process solvent for the production of wire enamels.
Direct uses of cresols are as bactericide in biotechnological processing, pesticide and other minor, wide dispersive
uses (< 1 % of worldwide production).
Information on releases into the environment from direct uses of cresols are not readily available.
RECOMMENDATIONThe chemicals in this category are currently of low priority for further work.

RATIONALE FOR THE RECOMMENDATION AND
NATURE OF FURTHER WORK RECOMMENDED
Human Health: m-Cresol, p-cresol and m/p-cresol mixtures possess properties indicating a hazard for humanhealth. Based on data presented by the Sponsor country, adequate risk management measures are being applied.
Countries may desire to check their own risk management measures to find out whether there is a need for measures
beyond those which are being applied already. Cresols (mixed isomers of ortho-, meta- and para-) are being tested
in carcinogenicity studies under the U.S. National Toxicology Program (NTP).
Environment: The chemicals possess 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 highexposure level, they should nevertheless be noted by chemical safety professionals and users.

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m- / p-CRESOLSIDS Initial Assessment Report
1

IDENTITY

1.1

Identification of the SubstanceChemical Names:
CAS Numbers:
Molecular Formula:
Structural Formula:m-Cresolp-Cresolm-/p-Cresol mixtures
m-Cresol
CAS No: 108-39-4
p-Cresol
CAS No: 106-44-5
m/p-Cresol CAS No: 15831-10-4
C7H8O
OH
OH

CH3
CH3
Molecular Weight:

m-Cresol
108.14 g/mol

p-Cresolm-Cresol, p-cresol and mixtures of both isomers are discussed in one SIAR because of their similar
properties in physico-chemical data, environmental fate, ecotoxicity, and toxicity. Both isomers aswell as their mixture are products of technical importance.
o-Cresol was subject of previous work in the OECD HPVC Programme. The Screening Information
Data Set (SIDS) has been published by OECD in 1998 (OECD 1998). Data for o-cresol are
therefore generally not included in this assessment.
Identification of the 3 Cresol Products of Technical Importance

Table 1Substance

Synonyms

CAS-No.

Composition

m-Cresol

3-Methylphenol

108-39-4

Purity > 99 %p-Cresol

4-Methylphenol

106-44-5

Purity approximately 99.9 %15831-10-4

60 - 75 % m-Cresol,
25 - 40 % p-Cresolm/p-Cresol
mixtures1.2

Physico-Chemical properties

The physico-chemical properties of the technical products are presented in table 2 (for references cf.
SIDS Dossiers).

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Table 2:

m- / p-CRESOL
Summary of Physico-Chemical Properties of Cresols

Substance

m-Cresolp-Cresolm/p-Cresol

Melting point [°C]

11.8

35.5

ca.10

Boiling point (1013 hPa) [°C]

202.2

201.9

ca. 200

Density (20°C) [g/cm3]

1.03361.0178ca. 1.035

Vapour pressure (25°C) [hPa]

0.147

0.147

Log Kow (exp.)

1.96

1.94

1.94 - 1.96

Water solubility (25°C) [g/l]

22.7

21.5

24.4

Dissociation constant pKa

10.09

10.26

Of particular importance for environmental behaviour and ecotoxicity are the values for partition
coefficient (log Kow), vapour pressure and water solubility. Water solubility, vapour pressure andlog Kow were experimentally determined for both isomers. The values are nearly identical for thepure isomers, so the isomer mixture can be assessed as well.
Cresols are weak acids. The pKa values of 10.09 and 10.26 for m- and p-cresol resp. indicate that at
environmental relevant pH values (5-9) the substances are largely non-dissociated in aqueous
solution.
1.3

Category Justification

The category justification is presented in the Annex.

2

GENERAL INFORMATION ON EXPOSURE

About 40 % (decreasing tendency) of the world-wide required cresols are isolated from the natural
sources coal tar and spent refinery caustics. The separation of phenolics is essentially a recovery,
purification, and fractional operation (Ullmann 2002).
The most important processes to obtain synthetic cresol mixtures with an usable content of the mand p-isomers are− alkaline chlorotoluene hydrolysis (higher m-cresol content)− sulfonation of toluene and alkali fusion (higher p-cresol content)− cleavage of cymene hydroperoxide (higher m/p- and low o-cresol content) (Ullmann 2002).
Only o-cresol can be separated directly from the crude cresol-mixtures by distillation. The m/pisomer mixture cannot be separated into the isomers by conventional distillation technology becauseof the low difference in the boiling points of this two isomers. There are different industrial
methods to separate the m- and p-isomers:− by distillation using an adsorption column process,− butylation of the mixture, distillation and debutylation of the separated butylkresols,− using a separation process via urea-cresol- adducts (Ullmann 2002).

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Table 3:m- / p-CRESOL

Estimated Capacities and Their Locations

Regionm/p-Mixture [1]Pure m-Cresol [2]Pure p-Cresol [2]WORLD

128,000 t

100 %28,500 t

100 %59,500100 %SE-ASIA

58,000 t

45 %14,500 t

51 %31,00052 %W-EUROPE

30,000 t

23 %8,000 t28 %13,000 t

22 %N-AMERICA

18,000 t

14 %6,000 t21 %12,500 t

21 %

OTHER

20,000 t

16 %3000 t5%

E-EUROPE

2000 t2%(Srour; 1 = stage October 2001, 2 = stage July 2000)
The largest part of cresols is used as intermediates in chemical processes:
Pure m-cresol (total processing in 1999 21,000 t) is mainly used as an intermediate for thefollowing products: for synthetic vitamin E (39 %), and in the synthesis of pesticides (insecticides,
herbicides, 29 %), fragrances and antioxidants (15 %), disinfectants and preservatives (12 %) andother chemicals (5 %) (Srour 2000) (e.g. photographic chemicals and explosives, ATSDR 1992;
HSDB 1993).
Pure p-cresol (production and demand in 1999 31,400 t) is used in chemical synthesis for theantioxidant BHT (49 %), other antioxidants (17 %), anisaldehyde (18 %), and other intermediates(16 %) which are used for production of pharmaceuticals, plant protection agents and dyestuffs(Srour 2000).
These figures for m- and p-cresol show that the actual production and demand is much below theestimated capacities given in Table 3.
m/p-Isomer mix is used to produce antioxidants (e.g. BHT, about 15,000 t/a) and arylphosphates(approximately 6000 t/a), the latter are used as plasticizers, flame retardants or special catalysts(Srour 2001).
m/p-Isomer mix is used as a solvent in the wire enamels business (49,000 t) (Srour 2000). In aclosed process the solvent, which evaporates during the drying of the wires, is burned. The burning
heat is used for heating the drying unit. Due to the waterfree process significant releases into thehydrosphere can be excluded. The emissions of cresols into the atmosphere from the application
wire enamels is controlled by national authorities in the EC (EC 1999).
Furthermore some direct uses of cresols are known (< 1 % of production):− m-Cresol is used by professionals as bactericide in the biotechnological processing ofpharmaceuticals (Bayer AG 2003)− m-Cresol is used as a preservative in pharmaceutical articles (injection solutions of insulin,
somatropin) (Rote Liste 2002)− m-Cresol is used as a pesticide for the treatment of the stems of fruit trees and plants: This is a
registered application and exclusively performed by professionals (HSDB 1993).
− Cresols (all isomers) are used as disinfectants, preservatives or stabilizers in cleaning/washing
agents, surface treatment products, paints, solvents, adhesives, binding agents and fillers(hardener), corrosion inhibitors, and impregnation materials. (Danish, Swedish, and Swiss
Product Register 2002)
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10,000 to 50,000 t/a cresol isomer mixture is produced at Bayer AG. Separation of the o-isomer
results in a m/p-cresol mixture yielding about 70 % m-cresol. More than 90 % of this product isprocessed inside the company to produce pure m-cresol (5000 – 10,000 t/a by butylation process),microbicides (chlorination), aroma stuffs (alkylation), plasticizers and pesticides. Production andprocessing take place in closed systems. About 15 % of the raw cresol mixture ex Bayer AG aresold as m/p-cresol mixture or as pure m-cresol.
Cresols occur widely in nature (many plants, cheese flavor and some other foods, petroleum, coaltar [in the carbolic oil fraction and in carbolineum (Roempp 1999);], crude oil, wood tars [e.g. in
Juniper tar oil, birch oils], volcanic actions, putrefaction). Pulich et al. (1975) mention cresols as aningredient of crude and fuel oils with an concentration of less than 1 %. They are emitted frommunicipal incinerators, during coal and wood combustion, with vehicle exhaust, and cigarettesmoke [e.g. component of the phenol fraction, which makes up 1 - 4 % of the smoke]. Cresols arealso products of the photooxidation of toluene in the atmosphere (Howard 1989).
In automotive exhaust m-cresol concentrations of 1.18 - 1.49 mg/m3 were detected (Kuwata et al.
1981). With 13 m3 exhaust gas per kg gasoline and a gasoline consumption of 56.5 Mio t/year forGermany m-cresole emissions to the environment of 867 to 1094 t/year via automotive exhaust arecalculated.
p-Cresol is an endogenous metabolite of the amino acid tyrosine and a normal constituent of humanurine with levels of excretion ranging from 16 to 74 mg/24 hours (Bone et al. 1976; Renwick et al.
1988). Based on this data a p-cresol emission to the environment of 467 to 2160 t/year can becalculated for the population of Germany (80 Mio).
The exhaust from production and processing of cresols in Germany are connected to exhaust
purification plants. Following the last Official German Emission Declaration in 2000 only 81 kg/a
Cresols were emitted into the atmosphere (Bayer AG 2000)
The emissions of cresols into the atmosphere from the application wire enamels is controlled bynational authorities in the EC (EC 1999).
In a special program the effluent of the waste water treatment plant at Bayer AG was monitored form-/p-cresols. All values of 22 effluent measurements were below the detection limit of 50 µg/l. For
the receiving water a PEC of < 7.1 x 10-2 µg/l is calculated taking into account the 10 percentile of
the river flow, the dilution factor, and the 90 percentile of the analysis measurements (Bayer AG
2003).
Recent monitoring data for cresols in the environment are not readily available. Older literatureshows data for areas which were mostly particularly polluted (Howard 1989). These data cannot be
used for a current evaluation.
Exposure to the environment may occur due to the use of cresol as a pesticide and other minor uses.
However, at present no quantification of the release is possible.
2.1

Environmental Exposure and Fate

2.1.1

Distribution

As the main physico-chemical properties of the cresol isomers are in the same order of magnitude,
the environmental distribution behaviour is expected to be similar.
The distribution of cresols in a ”unit world” was calculated according to the Mackay fugacity modellevel I (Bayer AG 2002a, b) based on the physico-chemical properties listed in table 1.2. For both,
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m-cresol and p-cresol the main target compartment was estimated to be water (96.3 %) (Calculated
distribution between environmental compartments: m-cresol resp. p-cresol: air: 2.33 / 2.46 %,water: 96.32 / 96.26 %, soil: 0.69 / 0.66 %, bottom sediment: 0.65 / 0.62 %, suspended sediment:
0.001 / 0.001 %, biota: 0.0004 / 0.0004 %). The distribution of cresols between aqueous solution
and air is described by the Henry’s law constant. Experimentally determined values of 0.09 Pa
m3/mol for m-cresol (Altschuh et al. 1999) and 0.10 Pa m3/mol for p-cresol (Gaffney et al. 1987)
are available. Both values indicate a low volatility from aqueous solution according to the criteria ofThomas (1990).
The distribution between the organic phase of soil solids and water was determined in batch
equilibrium experiments similar to the OECD Guideline 106. For a clay loam soil Boyd (1982)
determined Koc values of 34.58 for m-cresol and 48.66 for p-cresol indicating a low sorption
potential for the cresol isomers according to the criteria of Blume and Ahlsdorf (1993).
2.1.2

Abiotic Degradation

With regard to its chemical structure m-cresols and p-cresols are not expected to hydrolyse underenvironmental conditions.
Several investigations are available about the indirect photolysis by OH-radicals in the atmosphere.
In his critical review Atkinson (1994) recommended values for the reaction constant kOH at room
temperature of 6.4 x 10-11 cm3 molecule-1 s-1 for m-cresol and 4.7 x 10-11 cm3 molecule-1 s-1
for p-cresol. Based on a tropospheric OH radical concentration of 5 x 105 molecules cm-3
corresponding half-lives of 6.0 h for m-cresol and 8.2 h for p-cresol can be calculated. Semadeni etal. (1995) determined the temperature dependency of the reaction constants in a smog chamber
experiment: the calculated half-life is 3.8 h both for m-cresol (299 K) and p-cresol (301 K).
Because of the presence of a chromophore cresols are expected to undergo photolytical degradationin the hydrosphere. Scully and Hoigne (1987) determined the rate constants for the reaction of pcresol with singlet oxygen in a laboratory experiment. Solutions of p-cresol (<10-4 M) in 0.05 M
phosphate buffer were irradiated in a merry-go-round reactor, 5 mg/l rose bengal was used as asensitizer. The authors estimated a half-life of 21 d in surface water under noon summer sunlightand the latitude of Switzerland.
However, under environmental conditions longer half-lives should be expected since the solar
irradiation is considerably weakened due to light absorption and dispersion at greater water depths,
cloudiness and the diurnal fluctuations of light intensity.
2.1.3

Biodegradation

Aerobic
Several standard tests on the aerobic biodegradation of the cresol isomers are available. Table 4
presents an overview of the results:

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Table 4:m- / p-CRESOLStandard Tests on Aerobic Biodegradation of Cresols

MethodDurationm-Cresolp-Cresol

ReferenceOECD 301 D

28 d

65 - 90 %OECD 301 C

40 d

80 - 95 %80 - 95 %Desai et al. (1990)

OECD 302 B

10 d

96 %

100 %

Wellens (1990)5d

95.5 %

96 %Pitter (1976)

Bayer AG (2002c)

A Closed-Bottle-Test (OECD 301 D) using m-cresol as test substance in two concentrations (0.8mg/l and 2.4 mg/l) was performed (Bayer AG 2002c). While in two parallel experiments at a mcresol concentration of 0.8 mg/l nearly 90 % degradation was determined after 28 days incubation,at the test concentration 2.4 mg/l about 65 % degradation was achieved in two parallel vessels. At
both concentrations the pass level of 60 % was reached within 28 days. The 10d- window was
fulfilled in all but one parallel tests indicating that m-cresol can be considered as readily
biodegradable.
Desai et al. (1990) determined the Monod kinetics of m- and p-cresol using an electrolytic
respirometry test comparable to OECD guideline 301 C. Activated sludge from a wastewater
treatment plant receiving predominantly domestic sewage was used as inoculum in a concentrationof 30 mg/l. Within an incubation period of 40 days degradation of both cresol isomers (initialconcentration 100 mg/l) was in the range of 80 % to 95 %. The specific oxygen uptake curves of thecresols are not reported. However, the authors state that all test compounds revealed the same
pattern: the lag phase, biodegradation phase and the plateau region within a period of 10 days.
Therefore, it can be concluded from this test that m- and p-cresol are readily biodegradable. The
first order degradation constants ln(k) [h-1] were determined to be –5.77 (m-cresol) and –5.87 (pcresol). From these values half-lives of 9.3 d resp. 10.3 d can be calculated.
The inherent degradability of two cresol isomers was studied by Wellens (1990). In a test according
to the OECD guideline 302 B, m-cresol and p-cresol degraded to 95 % resp. 100 % within 10 days
after lag-periods of 2 days. Using a 5 days incubation period, Pitter observed that removal of each
96 % of both compounds occurred with the same initial degradation rate of 55 mg COD g-1 h-1.
Van Veld and Spain (1983) demonstrated that p-cresol is rapidly degraded in different parts of anaquatic estuary system. From a river estuary, each 3 samples were taken from water, sediment andintact eco-cores having an aerobic layer of detritus overlying anaerobic sediment. Water andwater/sediment samples were incubated in the laboratory with 14C-labelled p-cresol and shaken inflasks at 18 °C in the dark. Based on HPLC and 14CO2 measurements, half-lives between 9.4 and43 h for p-cresol in water and between 5.9 and 11 h in water/sediment systems were determined. In
intact eco-cores, p-cresol degraded with half-lives between 3.0 and 16 h.
The Closed-Bottle-Test (Bayer AG 2002c) reveals that m-cresol is readily biodegradable. As
demanded by the OECD guideline, the oxygen consumption was above 60 % after 10 and 28 days.
Desai et al. (1990) determined the degradation of both m- and p-cresol and found similar rate
constants for both isomers. From this study it can be concluded that both m- and p-cresol are readily
biodegradable.
Anaerobic:
The anaerobic degradation properties of a substance are important for the assessment of thesubstance’s fate during secondary digesting of sewage sludge and the fate in anaerobic sedimentlayers. A number of investigations on the anaerobic degradability of cresols is available. The most
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extensive study was conducted by Shelton and Tiedje (1981). Primary anaerobic sludges from 12
treatment plants receiving mainly domestic waste water were diluted to 10% in a mineral salt
medium and incubated with 30 mg cresol/l. Triplicate samples were incubated for 8 weeks.
Degradation was related to the theoretical CH4 and CO2 production. With m-cresol as the test
substance, no degradation was observed in 4 sludges, while in 6 sludges the degradation ranged
from 55 to 103 % after lag-periods of 4-6 weeks. For the experiments with 2 sludges the data wereinsufficient. In tests with p-cresol a degradation in the range of 62-101% was observed after lagperiods of 2 - 5 weeks (data for 1 sludge were insufficient). No explanation for the high variabilityof degradation results is given by the authors (Most of the results of this extensive study were also
published in a journal; Shelton and Tiedje 1984). Monitoring the formation of methane and carbon
dioxide, Battersby and Wilson (1989) obtained about 75 % of the theoretical yield of methane andcarbon dioxide from m-cresol during a > 60 days incubation period including a lag phase of 40days. For p-cresol the theoretical yield was 96 % during the same incubation period including a lagphase of 7 days.
As concluded above, m- and p-cresol can be considered as being readily biodegradable underaerobic conditions, thus it is unlikely that cresols released into waste waters or into surface waters
will reach the anaerobic zones. Therefore the anaerobic degradation is expected to be of minor
importance for the hazard assessment of cresols.
2.1.4

Bioaccumulation

Freitag et al. (1985) determined bioconcentration factors (BCF) of 14C-labelled m-cresol in fish
(Leuciscus idus melanotus). The fish were exposed to a 0.05 mg/l solution of the tests compound.
After the test period of 3 days radioactivity was measured in water medium and fish. A substancespecific analysis was not applied. BCF values of 20 were obtained.
In the same study BCF-values of 40 and 4900 for algae are reported without explanation for thedifference. Higher BCF values with algae may be obtained due to adsorption of test substance to thesurface of the algae and due to the high surface-volume ratio in the test. Thus the algal data were
not used in the assessment of the bioaccumulation potential.
The low BCF value for fish is supported by a BCF, estimated on the basis of the log Kow. Based on
the equation log BCFfish = 0.85. log Kow – 0.70 (EC 1996), a bioaccumulation factor (BCF) of 9.3
is calculated from the log Kow of 1.96 (m-cresol).
Experimental data for p-cresol are not available. Because of the similar log Kow, a similar
accumulation behaviour is expected. For m-, p-cresols and the mixture the bioaccumulation
potential is considered to be low.
2.2

Human Exposure

2.2.1

Occupational Exposure

The primary occupational exposure during manufacture and processing is via skin contact and, to alesser extent, through inhalation of the vapours. No information is readily available on the total
number of sites, which manufacture, process, or use cresols.
In Germany the workplace limit concentration is 22 mg/m³ (= 5 ppm) as TWA for the sum of all
cresol isomers (TRGS 900, 2002). The German exposure limit value is in accordance with that of
the other European countries limit values and with the US-TLV value.

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Investigations on cresols at the workplace have to be performed according to German regulations(TRGS 402). This includes regular surveys on exposure levels at different workplaces andappropriate control measurements.
At Bayer AG, 27 measurements of the workplace concentration were made between 1996 and 2001.
All values were below 2.0 mg/m³. The measurements were performed at different workplaces
during production, processing, sampling, and filling/drumming of m/p-cresols. 11 measurements areshort time values (mostly during sampling), the others are total shift values.
To protect workers from exposure to cresols at workplace, several different precautionary andprotective measures are taken including engineering controls, periodical personnel training andappropriate personal protection equipment for different work situations. Sampling takes place in an
automated manner with exhausting device. Filling/drumming is totally automated. In special
situations (e.g. maintenance/repair work) special personal protection equipment has to be worn (e.g.
self-contained breathing apparatus, full chemical protective clothing)
For on-site processing the m/p-cresols are transported in pipelines. For normal transport tocustomers m/p-cresols are transported in road tank trucks or rail tank wagons. Less then 10 % arefilled in special rolling channel drums.
Down stream professional users of cresols are informed by way of a material safety data sheet on
the recommended safety measures, including personal protective equipment (such as goggles, faceshields, gloves, aprons, personal respirators), and local and/or general ventilation systems. No
exposure measurements were available for workers involved in down-stream uses of m-Cresol, pCresol, and m/p-Cresol mixtures.
2.2.2

Consumer Exposure

The general public can be exposed to all isomers of cresol from air inhalation, food and beverageingestion and dermal contact.
Cresols (mixed isomers) are widespread in nature, occuring, for instance, in many plants,
petroleum, coal tar, crude oil and, volcanic actions. Foods, such as tomatoes, ketchup, asparagus,
cheeses, butter, bacon, and smoked foods, as well as beverages, such as red wine, raw and roasted
coffee and black tea, contain mixed cresols. Concentrations in spirit beverages were found to bewithin the range of 0.01 -0.2 mg/l (IPCS 1995). They are emitted from municipal incinerators,
during coal and wood combustion, with vehicle exhaust, from oil refineries, and cigarette smoke(ATSDR 1992). The amount in tobacco smoke is approximately 75 µg in a nonfilter cigarette(IPCS, 1995), and exposure to m/p-cresol from environmental tobacco smoke has been estimated to0.41 µg/m³ in adult Californian non-smokers (Miller et al. 1998). Cresols are also products of thephotooxidation of toluene (Howard 1989). m-Cresol and p-cresol were identified, but not
quantified, in the ambient outdoor air in the US (Shah and Singh, 1988). Combined m-/p-isomers
were detected in the ambient air of Portland/USA at a reported mean concentration of 1.3*10-7µg/m³ (0.03 ppb) (Grossjean 1991) and at a mean concentration of 1.4 µg/m³ (0 - 4.1 µg/m³) in the
US (Kelly et al. 1993). Combined m-/p-isomers were detected at a concentration of 0.04 µg/m³ in
Switzerland (Tremp et al. 1988). m/p-Cresols were found in USA outdoor air in concentrations of
0.038 - 0.411 µg/m³ in Minneapolis (MN) and of 0.053 - 0.408 µg/m³ in Salt Lake City (UT) in thewinter months. The range shows the different influence of residential wood burning and of traffic(Hawthorne et al. 1992). 3.9 x 10-4 µg/m³ (88 ppb) were found near a shale oil wastewater facility(Hawthorne and Sievers 1984).
m/p-Cresol isomers were detected in cloud water in the Vosges mountains/France (altitude about
800 - 1000 m) at concentrations of 0.47 - 2.23 mg/m³ and at 0.11 - 1.21 mg/m³ in the rain (Levsen
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et al. 1993). m/p-Cresol was found in rainfall in Switzerland at a concentration of 4.5 mg/m³(Tremp et al. 1988).
The lack of adequate monitoring data, however, makes quantitative estimates of daily intakes ofcresol from these sources practically impossible.
m-Cresol and p-cresol are permitted for direct addition to food for human consumption as
flavouring substances (EU 1999), and are used as perfumes and aromatic raw materials in cosmetic
products (SCCNFP 2000). m-Cresol is also used as preservative in cosmetics (BgVV 2001).
Exposure of humans is possible through the use of m-cresol as a preservative in pharmaceuticalinjection solutions (e.g. insulin injection solution 1.6 - 3 mg/ml) (Rote Liste 2002).
p-Cresol is used in cleaning/washing agents and in surface treatment products at concentrations up
to 2 % (Danish Product Register 2002).

3

HUMAN HEALTH HAZARDS

3.1

Effects on Human Health

3.1.1

Toxicokinetics, Metabolism and Distribution

All cresol isomers are absorbed across the respiratory and gastrointestinal tract and through theintact skin (Pereima 1977, Bray et al. 1950, Mandel 1971, DeBruin 1976, Roberts et al. 1977, IPCS
1995). Limited data indicate that cresols are widely distributed throughout the body after uptake(IPCS 1995). Cresols are mainly conjugated with glucuronic acid and inorganic sulfate and excreted
as conjugates with the urine (Bray et al. 1950). Minor pathways include hydroxylation of thebenzene ring (all isomers) and, for p-cresol, side-chain oxidation to p-hydroxybenzoic acid (Bray etal. 1950). For p-cresol, oxidation to a reactive quinone methide intermediate was also found in rat
liver in vitro (IPCS 1995, Thompson et al. 1996).
At physiological pH, the conjugated metabolites are ionized to a greater extent than the parent
compound, which reduces renal reabsorption and increases elimination with the urine (Mandel1971). In addition to urinary excretion, cresols are excreted in the bile, but the most part undergoes
enterohepatic circulation (IPCS 1995, Deichmann and Keplinger 1981, Scheline 1973). There are
known species differences in the specific conjugation reactions of cresol isomers and the relative
amounts of glucuronide and sulfate conjugates therefore differ between species and also vary withdose (Mandel 1971, Scheline 1973, IPCS 1995).
p-Cresol is an endogenous product of protein breakdown in humans. The anaerobic microflora of
the ileum reportedly produces this isomer from the amino acid tyrosine (Bone et al., 1976). p-Cresol
is a normal constituent of human urine with levels of excretion ranging from 16 to 74 mg/24 hours(Bone et al. 1976, Renwick et al. 1988, Schaltenbrand and Coburn 1985).
Conclusion:
m-Cresol, p-cresol and m/p-cresol mixtures are absorbed across the respiratory and gastrointestinal
tracts and through the skin, and are distributed throughout the body. The primary metabolic
pathway for all cresol isomers is conjugation with glucuronic acid and inorganic sulfates. All
isomers are mainly eliminated by renal excretion in form of conjugates. For p-cresol, oxidation to areactive quinone methide intermediate was found in rat liver in vitro.

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3.1.2

m- / p-CRESOLAcute Toxicity

There are no studies with m-, p-, or m/p-cresol mixtures according to the current OECD Test
guidelines, but there are studies which are adequately documented and are considered of sufficientquality to allow an evaluation of this endpoint:Oral
m-Cresol:
LD50 (male rat): 242 mg/kg bw (undiluted). Until 4 hours post application the animals showedhypoactivity, tremors, convulsions, salivation and prostration. Gross autopsy revealed inflammationof the gastrointestinal tract, and hyperemia of lungs, liver and kidneys only in the decedents
whereas the survivors showed no significant findings at the end of the 14 day observation period(BioFax 1969a). Given as 10 % olive oil solution the LD50 (rat) was 2020 mg/kg bw (Deichmann
and Witherup 1944).
p-Cresol:
Application of 100 - 316 mg/kg bw undiluted substance to 5 male rats/dose resulted in an LD50 of
207 mg/kg bw. As signs of intoxications were observed hypoactivity, tremors, lacrimation, dyspnea,
cyanosis, hemorrhagic rhinitis, convulsions, prostration and finally death occurred. Gross autopsy
revealed inflammation of the gastrointestinal tract in the survivors at the end of the 14 d observation
period. Haemorrhage of gastrointestinal tract, hyperemia of lungs, liver and kidneys were reported
from decedents (BioFax 1969b). Given as 10 % olive oil solution the LD50 (rat) was 1800 mg/kg bw(Deichmann and Witherup 1944).
m/p-Cresol:
There are no studies available using a m/p-cresol mixture.
Conclusion:
Following oral application the LD50 of undiluted m-cresol in rats was 242 mg/kg bw; and the LD50
of undiluted p-cresol was 207 mg/kg bw. Thus, it can be assumed that the LD50 of m/p-cresol
mixtures is slightly above 200 mg/kg bw. Clinical signs included hypoactivity, salivation, tremors,and convulsions.
Inhalation
m-Cresol:
In an 8 hour inhalation study rats were exposed to saturated vapour which was generated at room
temperature. No mortality occurred and no signs of intoxication were observed (Mellon Inst. Ind.
Res. 1949). These observations were in accordance with the inhalation study reported by BioFax(1969a): 6 male rats were exposed to 710 mg/m3 for 1 hour and then observed for 14 days. No rat
died and no signs of intoxication were observed. From gross autopsy, no pathological findings werereported. From a study in which m-cresol aerosols were used, the mean lethal concentration in rats
was reported to be 58 mg/m³ (exposure time not mentioned).. Clinical signs of toxicity included
irritation of mucous membranes, neuromuscular excitation and convulsions. Haematuria wasreported at very high concentrations (Pereima 1975).
p-Cresol
The exposure of 6 male rats to 710 mg/m3 p-cresol for 1 hour caused no mortality, and no signs ofintoxication. From gross autopsy no significant findings were reported (BioFax 1969b). From a
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study in which p-cresol aerosols were used, the mean lethal concentration in rats was reported to be
29 mg/m³. Clinical signs of toxicity included irritation of mucous membranes, neuromuscular
excitation and convulsions. Haematuria was reported at very high concentrations (Pereima 1975).
m/p-Cresol:
There are no data available using a m/p-cresol mixture.
Conclusion:
No mortality nor clinical signs of toxicity were seen following exposure to the saturated vapour
concentration of either m-cresol or p-cresol. Inhalation of aerosols may however cause death, andmean lethal concentrations in rats were reported to be 29 mg/m³ for p-cresol and 58 mg/m³ for mcresol. Clinical signs of toxicity included irritation of mucous membranes, excitation andconvulsions. Haematuria was reported at very high concentrations.
Dermalm-Cresol:
1000 - 3160 mg/kg bw undiluted m-cresol was applied to the skin of 5 rabbits per dose (exposure
time not mentioned, observation time: 14 days) yielding an LD50 of 2050 mg/kg bw. From 4 hours
post application up to 12 hours the animals showed lacrimation, salivation, hypersensitivity,
convulsions and hypoactivity; the treated skin showed severe erythema and burns. At gross autopsy,
the decedents showed hyperemia of lungs and kidneys whereas survivors showed no significant
findings. (BioFax 1969a). This result is in accordance with the results of another study, in which 24
hr exposure to the neat material was followed by a 14-day observation period. The LD50(rabbit) was
reported to be 2830 mg/kg bw (Vernot et al. 1977).
p-Cresol:
215 - 681 mg/kg bw undiluted p-cresol was applied to the skin of 5 rabbits per dose (exposure time
not mentioned, observation time: 14 days) yielding an LD50 of 300 mg/kg bw. From 4 hours post
application up to 12 hours the animals showed tremors, salivation, sedation and finally died. At theapplication site severe subdermal hemorrhaging and severe erythema were observed. At gross
autopsy, the decedents showed inflammation of the kidneys whereas survivors showed nosignificant findings (BioFax,1969b). This result is in accordance with the results of another study,
in which 24 hr exposure to the neat material was followed by a 14-day observation period. The
LD50(rabbit) was calculated to be 300 mg/kg bw (Vernot et al. 1977).
m/p-Cresol:
There is no study available using m/p-cresol-mixtures.
Conclusion:
Following dermal application in rabbits the LD50 of undiluted m-cresol was 2050 mg/kg bw and theLD50 of p-cresol was 300 mg/kg bw. It can be assumed that the LD50 of m/p-cresol mixtures is
between 300 and 2000 mg/kg bw.

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3.1.3

m- / p-CRESOL

Irritation

Skin Irritation
There is no study according to the current OECD Test guideline, but the available studies areadequately documented and are considered of sufficient quality to allow an evaluation of thisendpoint:
m-Cresol:
Application of 0.5 ml of the undiluted liquid to the intact or abraded skin of each of 6 rabbits caused
within 24 hours severe erythema and edema in each rabbit, which did not disappear within the 72
hours observation time (mean score value: 8.00/8.00) (BioFax 1969a). Using semi-occlusive
dressing for 4 hours, the visible tissue damage was indicative of corrosive effects (Vernot et al.
1977).
p-Cresol:
Application of 0.5 ml of the undiluted liquid to the intact or abraded skin of each of 6 rabbits caused
within 24 hours severe erythema and edema in the skin of each rabbit, which did not disappear
within the 72 hours observation time (mean score value: 8.00/8.00) (BioFax 1969b). Using semiocclusive dressing for 4 hours, the visible tissue damage was indicative of corrosive effects (Vernot
et al. 1977).
Application of 0.5 % p-cresol to the skin for 6 weeks resulted in permanent depigmentation of theskin and hair in black and agouti mice (Shelley 1974).
m/p-Cresol:
Undiluted m/p-cresol mixture was applied to the clipped intact skin of three male and female rabbits
for four hours covered by semiocclusive dressing and evaluated as corrosive because necrosis withsevere edema was noted 4 hours post application and eschar formation developed within 24 hours(Younger Lab 1974).
Conclusion:
m-Cresol, p-cresol and m/p-cresol mixtures are corrosive to the skin.
Eye Irritation
m-Cresol:
0.1 ml of the undiluted liquid caused highly irritating effects in the cornea, iris and conjunctivae ofall 6 treated rabbits. There was no recovery during the 72 hours observation period, and the mean
irritation score at 72 hours was 87.3/110 (BioFax 1969a).
p-Cresol
0.1 ml of the undiluted liquid caused highly irritating effects in the cornea, iris and conjunctivae ofall 6 treated rabbits. The effects did increase in severity during the 72 hours observation period, andthe mean irritation score at 72 hours was 93.0/110 (BioFax 1969b).
m/p Cresol:
There is no study available using a m/p-Cresol-mixture.

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Conclusion:
The instillation of undiluted m- or p-cresol into the rabbit eye according to the Draize method
resulted in extreme irritation with the risk of serious eye damage.
3.1.4

Sensitisation

m-Cresol:
There is no study available using m-cresol.
p-Cresol:
A modified Draize test was performed on 10 guinea pigs (males and females). Preliminary irritation
studies were performed to determine the suitable concentrations: the intradermal injection challenge
concentration was a 0.1 % solution and the application challenge concentration was a 10 %solution. p-cresol did not induce sensitization in guinea pigs (Sharp 1978).
Human data:
A maximization test was conducted on 25 volunteers using a 4 % concentration of p-cresol inpetrolatum. The maximization test involved an induction phase of 5 consecutive 48-hr covered
patch tests, sometimes separated by 24-hr periods of treatment with a mild irritant, followed 10 - 14days later by a 48-hr challenge patch using the same concentration. There were no sensitization
reactions in any of the volunteers (Kligman 1972).
m/p-Cresol:
In a study in which a 7.5 % solution of a mixture of m- and p-cresol in acetone was repeatedly
applied to the skin of guinea pigs, sensitization was not observed (DECOS, 1998).
Conclusion:
There is no indication of a sensitizing effect of p-cresol and m/p-cresol from a limited guinea pig
study and a limited human study. No sensitization test was available for m-cresol. In a survey article
hypersensitivity reactions of some individuals to cresol (isomer unspecified) have been mentioned(Deichmann and Keplinger 1981).
3.1.5

Repeated Dose Toxicity

Oral application
Regenerative changes in the nasal epithelia as a result of the irritant effects were the predominantsigns of toxicity following repeated dosing of rats and mice with p-cresol or with the 60:40 m/pcresol with the feed in 28-day and 13-week studies. At minimum effect levels of 1000 ppm in thediet (mouse, ca. 200 mg/kg bw/day) and 3000 ppm in the diet (rat, ca. 250 mg/kg bw/day), the liver
was the target organ for the toxic action of m-cresol, p-cresol and the 60:40 m/p-cresol mixture. A
dose-dependent increase in liver weight was observed, but histopathological effects or changes ofparameters indicative of liver toxicity were seen with p-cresol at high doses only. In the 13-week
feeding study with m/p-cresol transitory increases in serum total bile acids, alanine
aminotransferase and sorbitol dehydrogenase near the start of the study suggested that
hepatocellular injury with a decrease in hepatocellular function may have occurred and regressed in
the course of the study. Kidney weights were increased in male mice after feeding p-cresol for 28
days at 3000 ppm (469 mg/kg bw/day), and lengthened estrous cycles were noted in rats fed withthe m/p-cresol at 7500 ppm (509 mg/kg bw/day) in the 13-week study. In feeding studies bone
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marrow hypoplasia was found in rats after exposure to p-cresol at ≥ 3000 ppm (256 mg/kg bw/day),with m/p-cresol at 15,000 ppm, and in mice after exposure to p-cresol and m/p-cresol at 30,000
ppm.
Increased colloid within thyroid follicles in female rats were observed with m/p-cresol only at ≥ 509
mg/kg bw/day, but the biological significance of this observation is uncertain.
Based on the data from the subacute and subchronic studies there is no evidence to suggest that asignificant increase in toxicity occurs with longer exposures
In a poorly documented neurotoxicity study in rats with m-cresol and p-cresol, convulsions wereseen only in the groups treated with ≥ 450 mg/kg bw/day. Hypoactivity, rapid labored respirationand excessive salivation were observed sporadically at doses of ≥ 50 mg/kg bw/day. In spite of theobserved clinical signs, few significant changes were found in performance on neurobehavioural
test batteries, no brain weight changes were noted, and no gross or histopathological lesion in thebrain or other nervous tissues were found for any isomer (TRL 1986 as cited in IPCS 1995).
Results of repeated dose oral toxicity studies with m-cresol, p-cresol and m/p-cresol (60:40) aresummarized in the following tables:

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Table 5:m- / p-CRESOL

m-Cresol: Repeated Dose Toxicity Rat/Mouse

Study-Description

NOAEL

Effects

ReferenceRat
5 rats/sex/dose, 28 d, feeding
0, 300, 1000, 3000, 10,000,
30,000 ppm(m: 0, 25, 85, 252, 870, 2470
mg/kg bw/day;
f: 0, 25, 82,252, 862, 2310
mg/kg bw/day),

3000 ppm No mortality, no clinical signs of toxicity
(252
mg/kg
30,000 ppm, m, f: decreased body weight gain andbw/day)final body weight, decreased food consumption,
minimal to mild uterine atrophy in 4/5 females; nohistopathological changes in other organs

30 rats/sex/dose, 13 w gavage
0, 50, 150, 450 mg/kg bw/day incorn oil

Males: 50 450 mg: 1 male died (gavage error), lethargy, tremor,
mg/kg
hunched posture, dyspnoe, reduced body weight gain,
bw/daydecreased food consumption (m); no histopathologicalchanges≥ 10,000 ppm: increased rel liver weights

Females:150
mg/kg
bw/day10 rats/sex/dose, 13 w gavage
20 rats/sex as control
0, 50, 150, 450 mg/kg bw/day
in corn oil
neurotoxicity study
available as summary only

NTP 1991

Microbiolo
gical
Associates
Inc 1988a

150 mg: reduced bw gain (m)450 mg: reduced food consumption (m,f) convulsions, TRL 1986
death of 1 female, urination ↑ (f)*≥ 50 mg: clinical signs as salivation, urine wet
abdomen, hypoactivity, rapid and labored respiration,
myoclonus, hyperreactivity

Mouse
5 mice/sex/dose, 28 d feeding
0, 300, 1000, 3000, 10,000,
30,000 ppm(m: 0, 53, 193, 521,1730, 4710
mg/kg bw;
f: 0, 66, 210, 651, 2080, 4940
mg/kg bw)

1000 ppm(m: 193
mg/kg
bw/day),< 300
ppm (f, 66
mg/kg
bw/day)Mortality: 1/5 control male; 30,000 ppm: 2/5 f, 2/5 m; NTP 1991
10,000 ppm: 1/5 f
30,000 ppm, m,f: reduced body weight gain, and final
body weight, decreased food consumption, thinappearance, lethargy, tremor, hypothermia (f only), in
females atrophy of mammary gland, ovaries, uterus;
no histopathological changes in liver and kidneys≥ 10,000 ppm, m,f: hunched posture, rough hair coat,laboured breathing(only f)≥ 3000 ppm: increased rel liver weight (m)≥ 300 ppm: increased rel liver weight (f)* due to limitations in the study documentation, NOAELs were not derived

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Table 6:m- / p-CRESOL
p-Cresol: Repeated Dose Toxicity: Rat/Mouse

Study Description

NOAEL

Effects

ReferenceRat
5 rats/sex/dose, 28 d feeding
0, 300, 1000, 3000, 10,000,
30,000 ppm(m:0, 25, 87, 256, 835, 2180
mg/kg bw/day;
f: 0, 25, 83, 242, 769, 2060
mg/kg bw/day)

NTP 1991
No mortality
30,000 ppm,m,f: decreased feed consumption,
1000 ppm (m: decreased bw gain and final bw; hunched posture,rough hair coat, increased rel. liver and kidney weight,
87 mg/kg
bw/day, f: 83 uterus atrophy in 3 of 5 females; no histopathologicalchanges in liver or kidney.
mg/kg
bw/day) and1000 ppm≥10,000 ppm: increased rel liver, mild bone marrow(local)hypocellularity, in males increased rel kidney weight,
Systemic:≥3000 ppm: effects in nasal cavity indicative of
irritation; mild bone marrow hypocellularity in 1 of 5
males, increased rel liver weight in females
30 rats/sex/dose, 13 w gavage
50 mg/kg
0, 50, 175, 600 mg/kg bw/day in bw/day
corn oil

600 mg: in females death of 3 animals, lethargy,
salivation, tremor, convulsion, decreased body weight
gain, decreased food consumption (m), increased
SGPT (f) and SGOT (f), decreased ovary weight,
increased rel. liver weight (m) and increased rel
kidney weight, effects on trachea indicative of
irritation≥175 mg : decreased body weight gain (m), increased
serum protein (m), decreased red blood cell count, Hb, hematocrit-values (f)Microbiolo
gical
Associates
Inc 1988b

chronic nephropathy in all male animals, including thecontrols
10 rats/sex/dose, , 13 w gavage *20 rats/sex as control
0, 50, 175, 600 mg/kg bw/day incorn oilneurotoxicity study
available as summary only

600 mg: increased mortality (4m and4f; due toaspiration), reduced body weight gain (m), reduced
food consumption, reduced locomotor activity

TRL 1986≥ 50 mg: clinical signs as salivation, tremor, urine wet
abdomen, hypoactivity, myoclonus, rapid and labored
respiration, hyperreactivity

Mouse
5 mice/sex/dose, 28 d feeding
0, 300, 1000, 3000, 10,000,
30,000 ppm(m.: 0, 50, 163, 469, 1410, n.d.*
mg/kg bw/day;f.: 0, 60, 207, 564, 1590,n.d.*
mg/kg bw/day)* not determined

1000 ppm(systemic;
163/207
mg/kg
bw/day)30,000 ppm: death of all dosed mice: renal and hepatic NTP 1991
necrosis, bone marrow hypocellularity and renal
tubular necrosis and liver cell necrosis; in females
hunched posture, rough hair coat, lethargy,
hypothermia, laboured breathing, paleness300 ppm(local; m)

10,000 ppm: 1 m died,in males hunched posture, rough hair coat, lethargy,
hypothermia, laboured breathing, paleness, loweredbw gain and final bw, depressed food consumption at
the beginning; rel. liver- and heart-weight increased,in females depressed food consumption< 300 ppm
(local, f)≥3000 ppm, in females rel. liver weight increased, inmales rel. kidney weight increased

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m- / p-CRESOL≥300 ppm, f and ≥1000 ppm, m: nasal lesions
indicative of irritation* due to limitations in the study documentation, NOAELs were not derived

Table 7:m/p-Cresol (60:40): Repeated Dose Toxicity: Rat

Study Description

NOAEL

Effects

Reference

Systemic:
1000 ppm
(m;90
mg/kg
bw/day; f;
95 mg/kg
bw/day)No mortality

NTP 1991

Rat
5 rats/sex/dose, 28 d, feeding
0, 300, 1000, 3000, 10,000,
30,000 ppm(m: 0, 26, 90, 261, 877, 2600
mg/kg bw/day
f: 0, 27, 95, 268, 886,2570
mg/kg bw/day)

300 ppm(local)30,000 ppm, m, f: reduced bw gain, reduced foodconsumption, thin appearance, bone marrow
hypocellularity, no histopathological changes in liver orkidney≥ 10,000 ppm,f: increased rel. liver and kidney weight,
local effects at forestomach (m)≥ 3000 ppm: slightly increased rel. liver weight, (m,f)
increased colloid within follicles of the thyroid gland.
effects on oesophagus and forestomach (f only)
indicative of irritation≥ 1000 ppm (f) and ≥ 3000 ppm (m): effects in thenasal cavity indicative of irritation

20 rats/sex/dose, 13 week
feeding
0, 1880, 3750,7500, 15,000,
30,000 ppm,
(m: 0, 123, 241, 486, 991, 2014
mg/kg bw/day; f: 0, 131, 254,
509, 1024, 2050 mg/kg bw/day)Males:
1880 ppm
females:
3750 ppm(systemic,
123/254
mg/kg
bw/day)No mortality

NTP 1991

30,000 ppm: rough hair coat , urine stained fur, andthin appearance (f only), reduced feed consumption,
increased rel kidney weights (f), bone marrow
hypocellularity (f), decreased 5'Nucleotidase, increased
serum bile acids; no histopathological changes in liveror kidney< 1880 ppm ≥ 15,000 ppm reduced terminal body weight anddecreased body weight gain(f only), increased rel testes(local)weight, bone marrow hypocellularity (m), uterus
atrophy, increased colloid within thyroid follicles≥7500 ppm: increased rel liver weight and kidneyweight (m), increased colloid within thyroid follicles (fonly), lengthened oestrous cycle≥3750 ppm: increased abs. liver weight (m)≥1880 ppm: histological changes in nasal epitheliumindicative of irritation

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m- / p-CRESOLTable 8: m/p-Cresol (60:40): Repeated Dose Toxicity: Mouse
Study Description

NOAEL

Effects

Reference

Males:
300 ppm
females:1000 ppm(systemic;
50/200mg/kg
bw/day)No mortality

NTP 1991

Males:
3000 ppm.
Females:1000 ppm(local)≥ 10,000 ppm (m) and 30,000 ppm (f): reduced bodyweight gain

Mouse
5 mice/sex/dose, 28 d feeding
0, 300, 1000, 3000, 10,000,
30,000 ppm(m: 0, 50, 161, 471, 1490, 4530
mg/kg bw/day;
f: 0, 65, 200, 604, 1880, 4730
mg/kg bw/day)

30,000 ppm: alopecia, dehydration, hunched posture,
hypothermia, lethargy, rough hair coat, thin appearance,
reduced food consumption, weight loss, minimalchanges in lung, oesophgus and forestomach indicativeof local irritation, hypocellularity of the bone marrow,in females atrophy of ovaries and uterus; nohistopathological changes in other organs≥ 1000 ppm (m) and ≥ 3000 ppm (f): increased rel. liver
weights≥ 3000 ppm (f) and ≥ 10000 ppm (m): effects in thenasal cavity indicative of irritation

10 mice/sex/dose, 13 week
feeding
0, 625, 1250, 2500, 5000,
10,000 ppm(m: 0, 96, 194, 402, 776, 1513
mg/kg bw/day; f: 0, 116, 239,
472, 923, 1693 mg/kg bw/day)

Systemic:
5000 ppm(m, 776
mg/kg
bw/day),2500 ppm(f, 472
mg/kg
bw/day)No mortality

2500 ppm(local)≥ 5000 ppm (m) and ≥ 2500 ppm (f): effects in the nasal
cavity indicative of irritation

NTP 1991

10,000 ppm: rough fur (f), decreased food consumption,
reduced terminal body weight; no histopathologicalchanges in liver and kidney≥ 5000 ppm (m) and 10000 ppm (f): increased liver
weights

Inhalation RouteIn two studies, rats were administered the cresol isomers (isomers not specified) by the inhalationroute for 3 - 4 months at concentrations ranging from 0.05 to 10 mg/m³. In each study a decrease inbody weight gain, and histological changes in the liver and kidney were reported. Because of thelimited documentation regarding exposure methods, number of animals and results, these studies
cannot be adequately evaluated (IPCS 1995).
Dermal RouteNo data available.
Conclusion:
In 28-day and 13-week feeding studies, m-cresol, p-cresol and m/p-cresol (60:40) had a very similar
pattern of toxicity in rats and mice with minimal effect levels of 1000 - 3000 ppm in the diet (ca.
200 mg/kg bw/day in mice, ca. 250 mg/kg bw/day in rats) for increases in liver weight (rat, mouse)
and of 3000 ppm for increases in kidney weight (p-cresol; mouse, ca. 469 mg/kg bw/day). No
increase in relative kidney weight was found for m-cresol.
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m- / p-CRESOLAtrophy and regenerative changes in the nasal epithelia and forestomach were seen after exposure
to p-cresol and m/p-cresol, presumably as direct result of the irritant effects of these chemicals.
The no observed adverse effect levels (NOAELs) for m-cresol, p-cresol and m/p-cresol (28d- and90d-studies) were generally ≥ 50 mg/kg bw/day in rats and mice:
Table 9:NOAELsNOAEL Values for Systemic Toxicity From Repeated Dose Toxicity Studies
m-Cresolp-Cresolm/p-Cresol

252 mg/kg bw/day (m, f)

87 mg/kg bw/day (m)83 mg/kg bw/day (f)90 mg/kg bw/day (m),95 mg/kg bw/day (f)Rat(m, f):28d, feeding,

123 mg/kg bw/day (m)254 mg/kg bw/day (f)13 w, feeding
13 w gavage

50 mg/kg bw/day (m)150 mg/kg bw/day (f)50 mg/kg bw/day(m, f)

Mouse (m, f)
28 d feeding

163 mg/kg bw/day (m)193 mg/kg bw/day (m)207 mg/kg bw/day (f)66 mg/kg bw/day (f; LOEL:
increase in relative liver weight
without histopathologicalcorrelate)

50 mg/kg bw/day (m)200 mg/kg bw/day (f)776 mg/kg bw/day (m)472 mg/kg bw/day (f)13 w feeding

The NOAEL for repeated dose (90d-study) of o-cresol was 50 mg/kg bw/day for mice and rats
(UNEP 1998).
3.1.6

Mutagenicity

in vitro(A) Gene mutation
m-Cresolm-Cresol was tested negative in several Ames tests with various Salmonella typhimurium strains
and using preincubation or standard methodology (e.g. Haworth et al. 1983, Pool and Lin 1982).
The studies gave no indication of gene mutation with and without metabolic activation.
In addition, there is a mouse lymphoma assay with a negative result (with and without S9-mix,
Hazleton Lab. Am. 1988a).
p-Cresolp-Cresol was tested negative in several Ames tests with various Salmonella typhimurium strains andusing preincubation or standard methodology (e.g. Haworth et al., 1983, Pool and Lin, 1982). The
studies gave no indication of gene mutation with and without metabolic activation.
In addition, there is a mouse lymphoma assay (with and without S9-mix) with a negative result(Hazleton Lab. Inc. 1988e).

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m/p-Cresol
An Ames test was performed without S9-mix and with S9-mix from rat and hamster livers. The
studies gave no indication of gene mutations (NTP 1991).
Conclusion:
In vitro, m-,and p- cresol did not induce gene mutations in bacterial and mammalian cell systems
and m/p-Cresol mixture did not induce gene mutations in bacteria, both in the presence or absenceof metabolic activation.
(B) Cytogenicity
m-Cresol:
There is a study on cytogenicity (Chromosome aberration) using Chinese Hamster Ovary (CHO)
cells in vitro which corresponds to the current OECD guideline 473 (Hazleton Lab. Am. 1988b).
The study gave no indication of any clastogenic activity of the substance.
In addition, there is a mouse lymphoma assay (Hazleton Lab. Am. 1988a) with a negative result. In
a Sister Chromatid Exchange (SCE) test on human fibroblasts without metabolic activation no
increases in exchange rates were seen (Cheng and Kligerman 1984).
p-Cresol
There is a study on cytogenicity (Chromosome aberration) using Chinese Hamster Ovary (CHO)
cells in vitro which corresponds to the current OECD guideline 473 Incubated without metabolic
activation the assay was positive in all doses. The metabolic activated cultures which wereincubated for 10 hours yielded negative results and those which were incubated for 20 hours yielded
positive results (Hazleton Lab. Inc. 1988f). In addition, there is a mouse lymphoma assay with anegative result both in the presence or absence of metabolic activation (Hazleton Lab. Inc. 1988e).
In a Sister Chromatid Exchange (SCE) tests with human lymphocytes using a treatment time of up
to 90 hours (Jansson et al. 1986) and with human fibroblasts incubated with p-cresol for two hours(Cheng and Kligerman 1984), no increases in exchange rates were seen.
m/p-Cresol
There are no cytogenetic assays in vitro with a m/p cresol mixture.
Conclusion:
m-Cresol did not induce chromosomal aberrations in vitro, whereas p-cresol had clastogenic
activity in CHO cells in both the presence or absence of S-9 mix. It is therefore possible that m/pcresol mixture has the potential to induce chromosomal aberrations in vitro. Neither m- nor p-cresol
did increase SCE in vitro.
(C) Indicator test
m-Cresol
No induction of Unscheduled DNA Synthesis (UDS) was found in rat primary hepatocytes m(Hazleton Lab. Am. Inc. 1988c). In contrast, UDS was induced in SHE cells, but only in thepresence of a metabolic activation system (Hamaguchi and Tsutsui 2000).

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p-Cresolp-Cresol inhibited both UV-induced DNA repair synthesis and semiconservative DNA synthesis asevidenced by a reduction in radiolabelled thymidine incorporation (Daugherty and Frank 1986).
Induction of UDS was reported in Human Lung fibroblasts (Crowley and Margard 1978).
In vitro activation of p-cresol with either horseradish peroxidase or PB-induced rat liver
microsomes followed by incubation with calf-thymus DNA resulted in DNA adducts which are thesame as that produced by the quinone methide of p-cresol (Gaikwad and Bodell 2001).
m/p-Cresol
There are no data available using a m/p-cresol mixture.
Conclusion:
In vitro, p-cresol may induce unscheduled DNA synthesis, and the in vitro metabolite quinone
methide can form DNA adducts. Contradictory results for UDS induction were reported with mcresol from two studies both suffering from deficiencies. Thus, it is possible that m- and p-cresoland m/p-cresol mixtures have the potential to interact with DNA either directly or indirectly via
metabolites.
in vivo(A) Gene mutation
m-Cresol
There are no data available
p-Cresol
A Drosophila melanogaster SLRL test was negative following oral feeding of adult males with 0,60, 300 or 600 µg/ml for three days (Hazleton Lab. Am. 1989).
m/p-Cresol
There are no data available using a m/p-cresol mixture.
Conclusion
p-Cresol did not induce gene mutations in Drosophila melanogaster.
(B) Cytogenicity
m-Cresol:
There is a study on cytogenicity (chromosome aberration) in 5 mice/sex/group following single oral
application by gavage (0, 96, 320 and 960 mg/kg bw in corn oil) according to OECD guideline 475.
Signs of toxicity were observed for the two highest dose groups and included scruffy coats, squinty
eyes and difficulties in breathing. 3 male mice of the 960 mg-group were found dead during thestudy observation. m-Cresol revealed no clastogenic activity in bone marrow cells (Hazleton Lab.
Am. 1988d).
p-Cresol
To determine the potential of p-cresol to induce dominant lethal mutations in germ cells male micereceived single oral doses by gavage of 0, 100, 275 or 650 mg/kg bw suspended in corn oil.
Because of the excessive toxicity within the first week after dosing high dose animals were
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removed from the study and 550 mg/kg bw was assigned as the new high dose to be evaluated. pCresol did not induce dominant lethal mutations in the germ cells of male mice (Hazleton 1989a)
Single intraperitoneal injection of 0.75 mg/kg bw dissolved in sunflower oil was given to 2 or 3
intact or hepatectomized male mice. Negative and positive controls received sunflower oil (intact
and hepatectomized mice) and cyclophosphamid (intact mice), respectively. p-Cresol did not induce
significant increases in SCE frequencies in any of the cell types examined (Cheng and Kligerman
1984).
m/p-CresolGroups of 10 mice/dose were given 0, 625, 1250, 2500, 1000 and 10,000 ppm of a m/p-cresol
mixture (60:40). The mean test substance intake was 0, 96, 194, 402, 776, 1513 mg/kg bw/day formales and 0, 116, 239, 472, 923, 1693 mg/kg bw/day for females, respectively. To determine thefrequency of micronuclei in peripheral blood erythrocytes smears were prepared from blood
samples obtained by cardiac puncture of dosed and control mice at the termination of the 13 week
study. No significant elevation in the frequency of micronucleated erythrocytes was observed ineither male or female mice (NTP 1991).
Conclusion:
In vivo, m-cresol showed no clastogenic activity in mouse bone marrow cells, even at clearly toxic
dose levels (up to 960 mg/kg bw by gavage). p-Cresol did not induce dominant lethal mutations ingerm cells of mice after single oral doses that elicited marked toxicity (up to 550 mg/kg bw by
gavage). The sister chromatid exchange rate was not increased in mice after intraperitoneal injectionof 0.75 mg p-cresol/kg). m/p-Cresol mixture (60:40) did not elevate the frequency of
micronucleated erythrocytes in peripheral blood of mice fed for 13 weeks with up to 10,000 ppm.
Overall evaluation
In vitro, m- and p- cresol did not induce gene mutations in bacterial and mammalian cell systems
and m/p-Cresol mixture did not induce gene mutations in bacteria. m-Cresol was negative forclastogenic activity in vitro, and in vivo. p-Cresol, was clastogenic in vitro, but has not beenadequately tested in somatic cells in vivo. p-Cresol was, however, negative for dominant lethal
mutations in germ cells in male mice at clearly toxic exposure levels. A 60:40 m-/p-Cresol mixture
did not increase the frequency of micronucleated erythrocytes in the peripheral blood erythrocytesof mice. In vitro, it is possible that m- and p-cresol and m/p-cresol mixtures have the potential tointeract with DNA either directly or indirectly via metabolites.
Table 10:

Genotoxicity
Clastogenicity

Results of Mutagenicity Tests

In vitro

m-Cresolp-Cresolm/p-Cresol

negative

negative

negative

In vivonegative

In vitro

negative

positive

In vivonegative

negative

negativeo-Cresol can induce chromosomal aberrations and increase SCE in vitro but not in vivo (UNEP
1998).

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3.1.7

m- / p-CRESOL

Carcinogenicity

m-Cresol
There is no study available to assess the carcinogenic potential of m-cresol.
The promoting ability of m-cresol was investigated in the mouse skin painting model. The treatment
did induce an increase in skin papillomas, but not in carcinomas. The presence of benzene, which
was used as vehicle, did not appear to affect the results, since no papillomas were found in benzene
treated controls (Boutwell and Bosch 1959).
m-Cresol did not induce cell transformations in BALB/c-3T3 cells (Hazleton 1988g,h).
p-Cresol
There is no study available to assess the carcinogenic potential of p-cresol.
The promoting ability of p-cresol was investigated in the mouse skin painting model. The treatment
did induce an increase in skin papillomas, but not in carcinomas. The presence of benzene, which
was used as vehicle, did not appear to affect the results, since no papillomas were found in benzene
treated controls (Boutwell and Bosch 1959).
p-Cresol induced cell transformations in an in vitro cell transformation assay using mouse BALB/c3T3 cells without a metabolic activation system (Hazleton 1988g, h).
m/p-Cresol
There is no study available to assess the carcinogenic potential of a m/p-cresol mixture.
Conclusion:
As for o-cresol, there are no adequate data available to assess the carcinogenic potential of m- or por m/p-cresol mixture. From tumour promotion studies in mice there are some indications that
cresols may act as promoters.
Currently, the U.S. National Cancer Institute is performing a carcinogenicity feeding study on miceand rats with o/m/p-cresol mixture within the National Toxicological Program (NTP).
3.1.8

Toxicity for Reproduction

m-Cresol
Reproductive toxicity was examined in a two-generation study on Sprague-Dawley rats given 0, 30,
175 or 450 mg/kg bw/day in corn oil by gavage (BRRC 1989).
Effects on reproductive function or on morphology of reproductive tissues were not detected even atdoses producing overt toxicity in adult rats (hypoactivity, ataxia twitches, tremors, prostration urine
stains, audible respiration and perioral wetness). The NOAEL (fertility) was 450 mg/kg bw/day.
The NOAEL toxicity was 30 mg/kg bw/day.
In F1 and F2, litter size, sex ratio, and litter viability was unaffected by treatment. In F1 the female
pups had reduced body weights in the highest dose tested, but pup survival was not affected. In F2,
pup body weight, pup body weight gain and pup lactational index were reduced and pup mortality
was increased at the highest dose. Thus, the NOAEL (developmental effects) was 175 mg/kg
bw/day.

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m- / p-CRESOLIn the 13 week gavage study (0, 50, 50, 450 mg/kg bw/day in corn oil) with rats no effects on
reproductive organs were reported, neither in males nor in females (Microbiological Association
1988a).
p-Cresol
Reproductive toxicity was examined in a two-generation test on Sprague-Dawley rats given 0, 30,
175 or 450 mg/kg bw/day in corn oil by gavage (BRRC 1989).
Reproductive function was not affected in either of the two generations even at doses producing
overt toxicity in adult rats (hypoactivity, ataxia twitches, tremors, prostration urine stains, audible
respiration and perioral wetness). NOAEL (fertility): 450 mg/kg bw/day. NOAEL (toxicity): 30
mg/kg bw/day. p-Cresol caused increased stillbirths in the F1 and F2 generations: in F1 pups at 175(but not 450 mg/kg bw/day) and in F2 pups at 30 and 450 (but not at 175) mg/kg bw/day. There wassome variability in the number of stillborn in control groups in the F1 and F2 generation (2 versus0) and there was no clear dose-dependent effect in both generations (control/low/mid/high dose: F1
pups: 2/4/13/6; F2 pups:0/7/4/9). In F2 (but not F1) live birth indices were reduced at 30 and 450(not 175) mg/kg bw/day. Without any other effects, especially in the 30 mg/kg bw/day-group, it isunclear whether the effects on live birth indices were substance related. Pup survival indices in bothgenerations were not affected by treatment. A developmental NOAEL could therefore not be
determined from this study.
At 600 mg/kg bw/day a decrease in ovary weights and an increase in testes weights was observed ina 13-week gavage study with rats (Microbiological Associated 1988a).
m/p-Cresol
Male and female Swiss CD-1 mice were exposed to m/p-cresol (60:40) in the diet to assess
reproduction and fertility using the NTP continuous breeding protocol (RTI 1992):
Groups of 20 breading pairs received 0, 0.25, 1 and 1.5 % in feed for 7 days prior to cohousing andfor 98 days of continuous breeding. 40 breeding pairs received food only. The average daily intake
is calculated to be 0, 375, 1500 and 2250 mg/kg bw/day.
m-/p-Cresol mixture did not significantly affect most measures of reproductive competence in theF0-generation, including initial fertility, the proportion of pups born alive or the sex of pups born
alive. Adjusted live pup weight and the number of live pups per litter were decreased by 5 and 20%, respectively and cumulative days to the fifth litter were increased by almost 3 days in the highdose group compared to controls. Therefore the NOAEL (F0, fertility) was 1 % (approximately
1500 mg/kg bw/day).
F0 body weight and feed consumption were decreased at the 1.0 and 1.5 % dose levels, especially indelivering and lactating dams. At the 1.5 % level decreased body weight and increased kidney andliver weights of F0 animals were noted. Toxicity to reproductive organs at the 1,5 % dose level wasobserved in form of decreased epididymal and seminal vesicle weights by 10 and 21 %,respectively, with no changes in testes weight, sperm parameters or testicular and epididymal
histopathology. The NOAEL (F0, general toxicity) was 0.25 % (approximately 375 mg/kg bw/day).
In F1 animals of the high dose group, birth weights were decreased (5 %), and decreased
preweaning growth by 26 % and postweaning survival by 39 % were noted. Treatment related
clinical signs were reduced size, dehydratation, lethargy and rough coat in the high dose group. At
both, 1.0 and 1.5 % dose level male body and reproductive organ weights (prostate, seminal vesicle,
testes) were decreased and relative liver and kidney weights were increased but there were noeffects on sperm parameters or histology. Female terminal body weights were reduced at the twohighest dose levels as was the ovarian weight in all three dosed groups while liver and kidney
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weights were increased in all dosed groups. There was no effect of treatment on estrous cyclicity or
ovarian, liver or kidney histopathology. NOAEL (F1, general toxicity): 0.25 % (approximately 375
mg/kg bw/day).
In F1, m/p-cresol mixture had no effect of mating index, fertility index, pregnancy index. Numberof live F2 pups per litter, proportion of F2 pups born alive, and sex ratio of F2 pups was notaffected. Only live F2 pup weights and the adjusted live F2 pup weights of the 1.5 % dose groupwas significantly reduced. Thus, the NOAEL (F1, fertility) was 1 % (approximately 1500 mg/kg
bw/day).
No effects on sperm motility and concentration, and on oestrus cycle and vaginal cytology were
found following 13 weeks of feeding, groups of 10 mice/sex doses of up to 10,000 ppm (1513
mg/kg bw/day for males and 1693 mg/kg bw/day for females, respectively) (NTP 1991).
Following 13 weeks of feeding groups of 10 rats/sex doses up to 30,000 ppm (ca. 2014 mg/kg
bw/day for males and 2050 mg/kg bw/day for females) the only finding in males was a biologicallyinsignificant decrease (4 %) in mean sperm motility values which occurred at the high dose level. In
females, a dose-related increase in oestrous cycle length was observed at 7500 ppm (approximately
509 mg/kg bw/day) and 30,000 ppm; slight uterine atrophy was noted at 15,000 ppm (NTP 1991).
Conclusion
Despite general toxicity (hypoactivity, ataxia, twitches, tremors, prostration, urine stains, audible
respiration, perioral wetness), fertility was not affected by treatment with m-cresol or p-cresol(NOAEL, rat: 450 mg/kg bw/day). The NOAELs for general toxicity were determined as 30 mg/kg
bw/day. Fertility effects including a 20 % reduction in pup survival as well as reductions in theweights of male reproductive organs were found following treatment of mice with m/p-mixture in acontinuous breeding study at systemically toxic dose levels (reduced food consumption and reduced
body weights, increases in liver and kidney weights) (NOAEL, fertility and general toxicity: 0.25 %in feed (ca. 375 mg/kg bw/day)).
3.1.9

Developmental toxicity/Teratogenicity

m-Cresol
Developmental toxicity was examined in Sprague-Dawley rats and New Zealand White rabbits(BRRC 1988a, b).
m-Cresol was given to 25 pregnant rats/group by gavage on gestation day 6 - 15 at doses of 0, 30,
175 or 450 mg/kg bw/day dissolved in corn oil. At 450 mg/kg bw/day, there was a significant
reduction in periodic maternal body weights and weight gain during the dosing period. Clinicalsigns of toxicity at 450 mg/kg bw/day included hypoactivity, ataxia, tremor, twitches, prone
positioning, audible respiration, perioral wetness, and a reduction in food consumption. m-Cresol
did not induce fetotoxicity or malformations at any dose level tested. The NOEL for maternal
toxicity was 175 mg/kg bw/day and the NOEL for developmental toxicity was 450 mg/kg bw/day.
No fetotoxicity and no treatment-related effects on the incidence of any malformation (external,
visceral, skeletal) was found in the progeny of 14 rabbits/group, dosed by gavage on gestation day
6 - 18 with doses of 0, 5, 50, 100 mg/kg bw/day dissolved in corn oil. Clinical signs of toxicity wereobserved at 50 mg/kg bw/day (audible respiration and ocular discharge). The NOEL for maternal
toxicity was 5 mg/kg bw/day and the NOEL for developmental toxicity was 100 mg/kg bw/day.

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p-Cresol
Developmental toxicity was examined in Sprague-Dawley rats and New Zeeland White rabbits(BRRC 1988a, b).
p-Cresol was given to 25 pregnant rats/ group by gavage on gestation day 6 - 15 at doses of 0, 30,
175 or 450 mg/kg bw/day dissolved in corn oil. At 450 mg/kg bw/day, there was a significant
reduction in maternal body weight gain during the dosing period. Clinical signs of toxicity at 450
mg/kg bw/day included hypoactivity, ataxia, tremors, twitches, prone positioning, audible
respiration, and peroral wetness. p-Cresol caused fetotoxicity at 450 mg/kg/day, as evidenced by
reduced ossification in three skeletal districts. In addition, fetal body weight was reduced at 450
mg/kg/day. There was no treatment-related increase in the incidence of malformations (external,
visceral, skeletal) at any dose level. Gestational parameters which were unaffected by treatment
included number of ovarian corpora lutea, number of total, nonlive or live implants and sex ratio perlitter. Thus, the NOEL for maternal toxicity and developmental toxicity was 175 mg/kg bw/day.
No treatment-related effects on the incidence of any malformations (external, visceral, skeletal) was
found in the progeny of 14 rabbits / group, dosed by gavage on gestation day 6 - 18 with 0, 5, 50,
100 mg/kg bw/day dissolved in corn oil. Clinical signs of toxicity were observed at 50 and 100
mg/kg bw/day (audible respiration and ocular discharge, hypoactivity, gasping and cyanosis). There
were no treatment-related effects on food consumption and no treatment-related lesions in does orany changes in maternal organ weights. Gestational parameters were unaffected by treatment (notreatment related abortions, early deliveries or resorptions, and no changes in total, nonlive or live
implants per litter or fetal body weight per litter). Thus, the NOEL for maternal toxicity was 5
mg/kg bw/day and the NOEL for developmental toxicity was 100 mg/kg bw/day.
m/p-Cresol
There is no study available using a m/p-cresol-mixture.
Conclusion:
In developmental toxicity in rats and rabbits, no toxic effects on the developing organism could befound despite of the toxic effects of m-cresol on the dams as evidenced by hypoactivity, ataxia,
tremor, twitches, prone positioning, audible respiration, perioral wetness, and a reduction in foodconsumption in rats, and audible respiration, and ocular discharge in rabbits (NOELs: 175 mg/kg
bw/day (maternal toxicity) and 450 mg/kg bw/day (developmental toxicity) for rats, and 5 mg/kg
bw/day (maternal toxicity) and 100 mg/kg bw/day (developmental toxicity) for rabbits,
respectively).
p-Cresol caused fetotoxicity (delayed ossification, decreased fetal body weight) at maternally toxic
dose levels in rats (NOAEL maternal toxicity, developmental toxicity: 175 mg/kg bw/day). In
rabbits, p-cresol caused no developmental effects even at doses that were maternally toxic (NOEL
maternal toxicity, developmental toxicity: 175 mg/kg bw/day).
Based on the available data it can be assumed that the m-/p-cresol mixtures may have the potential
to induce fetotoxicity in the presence of maternal toxicity.
3.1.10 Other relevant information
Experience with human exposure
The effects of (intentional or accidental) oral intake of cresols (all isomers) are described in several
case reports. The effects comprise irritation of mouth and throat, abdominal pains, vomiting,haemolytic anemia, increased heart rate, liver and kidney damage, headaches, facial paralysis,
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drowsiness, cramps, coma and death (Bruce et al. 1976, Cote et al. 1984, Minami et al. 1990,
DECOS 1998).
Skin contact has also resulted in effects on the nervous system, liver and kidneys, and caused
human fatalities (DECOS 1998). A cresol solution, unintentionally poured over the trunk, caused
gross haematuria, gastrointestinal bleeding, hypertension and septic shock with severe jaundice andrenal failure (Lin and Yang 1992).
Accidental dermal exposure of both legs and face of a 47 old man to m-cresol resulted in corrosionof 15 % of his body surface and he developed acute polyuric renal failure (Evers et al. 1994).
Skin depigmentation (chemical leukoderma) has been reported after local exposure to cresols (NTP
1991).
No data on systemic effects following acute and short-term occupational exposure to cresol vapoursor aerosol were located (DECOS 1998). 7 workers who were exposed to unknown concentrations ofcresol vapour for 1½ to 3 years, suffered from frequent headaches, nausea and vomiting. Four of theworkers had high blood pressure, impaired renal function, abnormal blood calcium levels anmarked tremor (DECOS 1998).
No epidemiological studies or case reports on occupationally exposure to cresols were foundcontaining adequate details on exposure levels. Anomalous menstrual cycles and hormonal
disorders were reported for women who were employed in the production of enamelled wire or of
tricresyl phosphate and were exposed in the process to a variety of compounds, including
chlorobenzenes and phosphoryl chloride. It was claimed that the incidence of perinatal child death
was increased and that developmental disorders were frequent among the new-born babies. Since nodata on exposure levels and duration of exposure are given, and data on controls were not provided,a relationship between the described effects and cresol exposure cannot be deduced (DECOS 1998).
The human lethal dose (LD) is reported to be 50 - 500 mg/kg bw (Gleason et al. 1969).
The development of tumours in persons who had been exposed occupationally to cresol(unspecified isomer) has been reported, and two cases of transitional cell bladder carcinoma were
described after long-term exposure to cresol (Garrett 1975). Another case involved a worker in an
oil refinery who was exposed to cresol, dichlorooctane and chromic acid for a long period and who
developed a squamous epithelial carcinoma of the vocal cords (DECOS 1998). Since no
information on exposure levels are available, and since co-exposure to other substances cannot be
excluded, a carcinogenic potential of the cresol isomers cannot be deduced from these case reports(DECOS 1998).
According to the results of studies in cancer patients, endogenous p-Cresol does not contributesignificantly to the development of human bladder cancer (32 patients vs 32 age/sex-matched
controls, Renwick 1988) or large bowl cancer (18 patients versus 10 normal healthy persons, Boneet al. 1976).
Conclusion:
In humans, the accidental oral uptake of cresols can induce irritation of mouth and throat,
abdominal pains, vomiting, haemolytic anemia, increased heart rate, liver and kidney damage,headaches, facial paralysis, drowsiness, cramps, coma and death. Skin contact with cresols canresult in corrosion, skin depigmentation, effects on the nervous system, liver and kidneys,
gastrointestinal bleeding, and can cause human fatalities. There are some case reports about tumor
development in connection with probable exposure against cresol isomers. Since co-exposures toother substances cannot be excluded, no conclusion on a carcinogenic potential can be deduced
from these case reports.
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3.2

m- / p-CRESOL

Initial Assessment for Human Healthm-Cresol, p-cresol and m/p-cresol mixtures are absorbed across the respiratory and gastrointestinal
tracts and through the skin, and are distributed throughout the body. The primary metabolic
pathway for all cresol isomers is conjugation with glucuronic acid and inorganic sulfates. All
isomers are mainly eliminated by renal excretion in form of conjugates. For p-cresol, oxidation to areactive quinone methide intermediate was found in rat liver in vitro.
The oral LD50 of undiluted m-cresol in rats was 242 mg/kg bw; and the LD50 of undiluted p-cresol
was 207 mg/kg bw. Thus, it can be assumed that the LD50 of m/p-cresol mixtures is slightly above
200 mg/kg bw. Clinical signs included hypoactivity, salivation, tremors, and convulsions. No
mortality or clinical signs of toxicity were seen following exposure to the saturated vapour
concentration of either m-cresol or p-cresol. Inhalation of aerosols may however cause death, andmean lethal concentrations in rats were reported to be 29 mg/m³ for p-cresol and 58 mg/m³ for mcresol. Clinical signs included irritation of mucous membranes, excitation and convulsions.
Haematuria was reported at very high concentrations. Following dermal application in rabbits theLD50 of undiluted m-cresol was 2050 mg/kg bw and the LD50 of p-cresol was 300 mg/kg bw. It
can be assumed that the LD50 of m/p-cresol mixtures is between 300 and 2000 mg/kg bw.
m-Cresol, p-cresol and m/p-cresol mixtures are corrosive to the skin and may cause serious damage
to the eyes. There is no indication of a sensitizing effect of p-cresol and m/p-cresol from a limited
guinea pig study and a limited human study. No sensitization test was available for m-cresol. In a
survey article hypersensitivity reactions of some individuals to cresol (isomer unspecified) havebeen mentioned.
In 28-day and 13-week feeding studies, m-cresol, p-cresol and m/p-cresol (60:40) had a very similar
pattern of toxicity in rats and mice with minimal effect levels of 1000 – 3000 ppm in the diet forincreases in liver weight (rat, mouse) and kidney weight (mouse, p-cresol). No increase in relative
kidney weight was found for m-cresol. Atrophy and regenerative changes in the nasal epithelia andforestomach were seen after exposure to p-cresol and m/p-cresol, presumably as direct result of theirritant effects of the chemicals. The no observed adverse effect levels (NOAELs) for m-cresol, pcresol and m/p-cresol were generally ≥ 50 mg/kg bw/day in rats and mice.
In vitro, m-cresol and p-cresol did not induce gene mutations in bacterial and mammalian cellsystems and m/p-cresol mixture did not induce gene mutations in bacteria. m-Cresol was negative
for clastogenic activity in vitro, and in vivo. p-Cresol was clastogenic in vitro, but has not beenadequately tested in somatic cells in vivo. p-Cresol was, however, negative for dominant lethal
mutations in germ cells in male mice at clearly toxic exposure levels. A 60:40 m/p-cresol mixture
did not increase the frequency of micronucleated erythrocytes in the peripheral blood erythrocytesof mice. In vitro, it is possible that m- and p-cresol and m/p-cresol mixture have the potential tointeract with DNA either directly or indirectly via metabolites.
As for o-cresol, there are no adequate data available to assess the carcinogenic potential of mcresol, p-cresol or m/p-cresol mixtures. From tumour promotion studies in mice there are someindications that cresols may act as promoters. Currently, the U.S. National Cancer Institute is
performing a carcinogenicity feeding study on mice and rats with cresols (mixture of ortho-, metaand para-) within the National Toxicological Program (NTP).
Despite general toxicity (hypoactivity, ataxia, twitches, tremors, prostration, urine stains, audible
respiration, perioral wetness) fertility was not affected by treatment with m-cresol or p-cresol(NOAEL, rat: 450 mg/kg bw/day). The NOAELs for general toxicity were determined as 30 mg/kg
bw/day. Fertility effects including a 20% reduction in pup survival as well as reductions in theweights of male reproductive organs were found following treatment of mice with m/p-cresol
mixture in a continuous breeding study at systemically toxic dose levels (reduced food consumption
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and reduced body weights, increases in liver and kidney weights) (NOAEL, fertility and general
toxicity: 0.25 % in feed (ca. 375 mg/kg bw/day).
In developmental toxicity studies with m-cresol in rats and rabbits, no toxic effects on thedeveloping organism could be found despite of the toxic effects on the dams as evidenced byhypoactivity, ataxia, tremor, twitches, prone positioning, audible respiration, perioral wetness, and areduction in food consumption in rats, and audible respiration, and ocular discharge in rabbits(NOAELs: 175 mg/kg bw (maternal toxicity) and 450 mg/kg bw (developmental toxicity) for rats,
and 5 mg/kg bw (maternal toxicity) and 100 mg/kg bw (developmental toxicity) for rabbits,
respectively. p-Cresol caused fetotoxicity (delayed ossification, decreased fetal body weight) atmaternally toxic dose levels in rats, but not in rabbits (NOAEL, rat, maternal toxicity,
developmental toxicty: 175 mg/kg bw/day). Based on the available data, it can be assumed thatm/p-cresol mixtures may have the potential to induce fetotoxicity in the presence of maternal
toxicity.
In humans, the accidental oral uptake of cresols can induced irritation of mouth and throat,
abdominal pains, vomiting, haemolytic anemia, increased heart rate, liver and kidney damage,headaches, facial paralysis, drowsiness, cramps, coma and death. Skin contact with cresols canresult in corrosion, skin depigmentation, effects on the nervous system, liver and kidneys,
gastrointestinal bleeding, and can cause human fatalities.
There are some case reports about tumour development in connection with probable exposure
against cresol isomers. Since co-exposures to other substances cannot be excluded, no conclusion
on a carcinogenic potential can be deduced from these case reports.

4

HAZARDS TO THE ENVIRONMENT

4.1

Aquatic Effects

For the effects assessment of cresols on aquatic organisms their ready biodegradability in aqueous
solutions has to be taken into account. In static tests with analytical monitoring Falk-Petersen et al.
(1985) found less than 10 % loss of the test substance after 4 days, thus short term tests without
analytical monitoring can be accepted as valid.
Fish
Valid tests on acute toxicity to fish are available for 14 freshwater and 1 marine species. An
overview is presented in table 4.1.
A flow-through test on the acute toxicity of p-cresol to Pimephales promelas was conducted byGeiger et al. (1986). The fish were exposed in Lake Superior water to 5 test substanceconcentrations. Analytical measurements revealed that the cresol concentrations were stable during
the test period. Based on measured concentrations a 96h-LC50 of 16.5 mg/l was obtained. The
affected fish lost schooling behaviour, swam near the tank surface, were hyperactive andoverreactive to external stimuli, they had increased respiration and lost equilibrium prior to death.
DeGraeve et al. (1980) conducted flow-through bioassays on the toxicity of m- and p-cresol to
Pimephales promelas and Oncorhynchus mykiss. The fish were exposed in well-water to 7
concentrations of the test substances and one control. O. mykiss was the more sensitive species with
LC50 values of 8.9 mg/l for m-cresol and 7.9 mg/l for p-cresol; the LC50 values for P. promelas
were 55.9 mg/l for m-cresol and 28.6 mg/l for p-cresol. All effect values are based on measured
concentrations.

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Table 11:

m- / p-CRESOL

Toxicity of m- and p-Cresol to Fish in Short-term Tests

Species

Test type

ExposureperiodEffects [mg/l]
m-Cresol

Pimephales promelas

96 hflow through96 hstaticp-Cresol
EC50 = 16.5 (e)Geiger et al. (1986)*

LC50 = 28.6 (e)DeGraeve et al. (1980) *96 h

LC50 = 15.5 (n)Howland (1969)

static96 h

LC50 = 19 (n)Mattson et al. (1976)

flow through96 h

LC50 = 7.9 (e)DeGraeve et al. (1980) *flow through96 h

LC50 = 7.5 (e)Hodson et al. (1984)

static96 h

LC50 = 8.6 (n)LC50 = 7.4 (n)Howland (1969)

Brachydanio rerio

static96 h

LC50 = 15.9 (n)Lepomis macrochirus

static96 h

Leuciscus idus

static48 hSalmo trutta

staticSalvelinus fontinalis

Oncorhynchus mykiss

flow throughReference

LC50 = 55.9 (e)LC50 = 8.9 (e)Wellens (1982)
LC50 = 7.1 (n)Howland (1969)

LC50 = 17 (n)LC50 = 11 (n)Ruebelt et al. (1982)96 h

LC50 = 8.4 (n)LC50 = 4.4 (n)Howland (1969) *static96 h

LC50 = 7.6 (n)LC50 = 5.8 (n)Howland (1969) *Poecilia reticulata

semistatic

96 h

LC50 = 23.1 (n)Cyprinus carpio

static96 hGadus morrhua (eggs)

static96 h

Ictalurus melasstaticIctalurus punctatus

Saarikoski andViluksela(1982)
LC50 = 13.3 (n)Howland (1969)

EC50 = 5.0 (e)Falk-Petersen et al. (1985)96 h

LC50 = 57.5 (n)Howland (1969)

static96 h

LC50 = 39.7 (n)Howland (1969)

Perca flavescens

static96 h

LC50 = 10.0 (n)Howland (1969)

Gambusia affinis

static96 h

LC 50 =33 (n)Sangli and Kanabur (2000)

Lepidocephalichthys guntea

semistatic

96 h

LC50 = 14.0 (n)Kanabur and Sangli (1998)

EC50 > 30 (e)(n): nominal concentration * : studies which are flagged as key studies(e): effective concentration

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The most sensitive fish species in acute toxicity tests belong to the salmonids. Howland (1969)
conducted static tests on the toxicity of m-cresol to three trout species and of p-cresol to 9 fish
species. Among the tests with m-cresol Salvelinus fontinalis was most sensitive exhibiting a LC50
of 7.6 mg/l, while with p-cresol as the test substance the lowest LC50 was found for Salmo trutta(4.4 mg/l).
The effect values from tests on m- and p-cresols indicate toxicity in the same order of magnitude,with p-cresol being slightly more toxic.
A chronic toxicity test (early life stage) with P. promelas was conducted with p-cresol over a periodof 32 days. A NOEC of 1.35 mg/l was obtained. This is a nominal concentration (Barron andAdelman 1984). It has to be regarded that Pimephales promelas was not the fish species being mostsensitive in short-term tests.
Invertebrates
The acute toxicity of m-cresol to Daphnia magna was determined in a static immobilization test
after an exposure period of 24 h. Duplicate samples with each 10 individuals of 24 h old daphnids
were exposed to the test solutions. Analytical control was not performed. The nominal EC50 was
reported to be 25 mg/l (graphically determined) (Bringmann and Kühn 1982).
A comparable test was conducted with p-cresol. Kühn et al. (1988, 1989a) exposed each 20
daphnids in 4 replicates to p-cresol, the nominal EC50 was graphically determined to 4.9 mg/l.
The 3 valid test results, available for the short-term toxicity of m- and p-cresol on Daphnia magna,
allow a comparison of the acute toxicity of both substances on this species. The results demonstrate
a similar toxicity of both isomers.
Long-term tests to invertebrates are only available for p-cresol. In a semi-static test with Daphnia
magna, each 20 individuals (24 h old) in 4 replicates were exposed to p-cresol in a concentration
range of 0.003 - 10 mg/l. The test solutions were renewed 3 times per week, their stability wascontrolled by analytical monitoring. After 21 days of exposure a NOEC of 1 mg/l was determined(Kühn et al. 1988, 1989a).
Aquatic Plants
The cell multiplication inhibition of p-cresol on the alga Scenedesmus subspicatus was tested byKühn and Pattard (1990). The algae were exposed to concentrations between 0.8 and 100 mg/l.
Analytical control was not performed. Based on nominal concentrations a 48 h-EC50 of 21 mg/l andan EC10 of 4.6 mg/l (both related to growth rate) were determined.
In a study with macrophytes (Nobel 1983) NOEC-values for the endpoint photosynthesis (oxygen
production) of 0.22 mg/l to 1.08 mg/l for m-cresol and < 0.22 mg/l to 1.08 mg/l for p-cresol arereported and provide a hint towards higher sensitivity of macrophytes to cresols. However, as no
information is given about substance application, test design (no. of plants per vessel andreplication) and control performance, the study is considered invalid and is not used for the PNEC
derivation.

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Table 12:m- / p-CRESOL
Tests on Acute Toxicity of m-and p-Cresol to Invertebrates

Species

Test type

Daphnia magna

Daphnia pulicaria

ExposureperiodEffects [mg/l]
m-Cresol

Reference
p-Cresol

Static24 hEC50 = 4.9 (n)Kühn et al. (1988, 1989a) *Static48 h

EC50 = 7.7 (n)Kühn et al. (1989b)

Static24 hEC50 =19.2 (n)EC50 =12.4 (n)Devillers et al. (1987, 1988)

static24 hEC50 = 25 (n)Bringmann and Kühn (1982) *static24 hEC50 = 8.9 (n)Bringmann and Kühn (1977a) *flow through48 hEC50 > 99.5 (e)EC50 = 22.7 (e)DeGraeve et al. (1980) *(n): nominal concentration(e): effective concentration*: studies which are flagged as key studies

Table 13:

Tests on Long-term Toxicity of m-and p-Cresol to Fish and Invertebrates

Species

Test type

ExposureperiodEffects [mg/l]
m-Cresol

Reference
p-Cresol

Pimephales promelas

Early life stage

32 d

NOEC = 1.35 (n)Barron and Adelmann (1984)*

Daphnia magna

semistatic

21 d

NOEC = 1.0 (n)Kühn et al. (1988, 1989a) *Dugesia tigrina(aquatic flatworm)

semistatic

80 d

LC10 =2.0 (n)LC0 = 1.0 (n)Solski and Piontek (1987)(n): nominal concentration(e): effective concentration*: studies which are flagged as key studies

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Table 14:

m- / p-CRESOL
Toxicity of m- and p-Cresol to Aquatic Plants

Species

ExposureperiodScenedesmus subspicatus

48 h

Chlorella pyrenoidosa

72 hEffects [mg/l]
m-Cresol

EC50 = 127 (n)Endpoint

Reference

EbC10 = 2.3 (n)ErC10 = 4.6 (n)EbC50 = 7.8 (n)ErC50 = 21 (n)Biomass
Growth rate

Kühn and Pattard (1990) *EC50 = 116(n)Chlorophyll
content

Huang and Gloyna (1968)

p-Cresol(n): nominal concentration(e): effective concentration*: studies which are flagged as key studies

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Summary of aquatic effects:
The available ecotoxicity data for m- and p-cresol show that the toxicity of the two isomers is in thesame order of magnitude within the uncertainty range of laboratory effect tests. Long-term tests are
only available for p-cresol. However, from the similarity in acute toxicity testing, it can be expectedthat the long-term toxicity of both isomers is similar as well. For the isomeric mixture m/p-cresol noecotoxicity data are available. However, it is expected that the toxicity of the isomeric mixture iscovered by the data for m- and p-cresol. Therefore, for the hazard assessment of this category, allavailable ecotoxicity tests are considered together, independent from the isomer for which they
were determined.
Determination of PNECaqua
Results from long-term tests are available for fish, invertebrates and algae, the most sensitive
species being Pimephales promelas (NOEC = 1.35 mg/l), Daphnia magna (NOEC = 1 mg/l) and
Scenedesmus subspicatus (ErC10 = 4.6 mg/l). Applying an assessment factor of 10 to the lower
value, the Predicted No Effect Concentration (PNEC) for the aquatic compartment is determined form- and p-cresol and the isomeric mixture m/p-cresol: PNECaqua = 0.1 mg/l.
QSAR estimations using ECOSAR for phenolic compounds result in the following values:fish:

30d-NOEC = 2.216 mg/l
90d-NOEC = 0.121 mg/l

daphnia:

21d-NOEC = 1.571 mg/l

The values for the 30d fish test and the 21d daphnia test are in good agreement with theexperimentally determined values. Therefore, it cannot be excluded that a prolongation of the
exposure period in fish tests would result in a NOEC that is about an order of magnitude below theavailable NOEC of 1.35 mg/l. This would have also consequences for the PNECaqua.
Microorganisms
In a respiration inhibition test using activated sludge according to OECD 209 with m-cresol as test
substance, a 3 h-EC50 of 461.4 mg/l was obtained (Klecka and Landi 1985). In a similar test with pcresol, the 2 h-EC50 was 439.5 mg/l (Chan et al. 1999). Tomlinson (1966) studied the inhibition of
the first nitrification step (oxidation of NH4 to NO2) and obtained 4 h-EC75 values of 11.4 mg/l for
m-cresol and 16.5 mg/l for p-cresol.

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Table 15:

m- / p-CRESOL
Toxicity of Cresols to Microorganisms

Species

Domestic sewage sludge

ExposureperiodEffects [mg/l]
m-Cresol2hEndpoint

Reference

respiration

Chan et al. (1999) *respiration

Klecka andLandi (1985) *p-Cresol
EC50 = 439.53hEC50 = 461.44hEC75 = 11.4

EC75 = 16.5

nitrification

Tomlinson (1966) *Nitrosomonas sp.

24 h

EC50 = 0.78 **EC50 = 27

nitrification

Blum and Speece (1991)

Pseudomonas putida

16 h

EC3 = 53

cell multipl.

Bringmann and Kühn (1976)

Tetrahymena pyriformis(protozoa)

24 hEC50 = 157

growthSchultz et al. (1996)

24 h

EC50 = 160

growthYoshioka et al. (1985)

Entosiphon sulcatum(protozoa)

72 h

EC5 = 31cell multipl.

Bringmann (1978)

Chilomonas paramaecium(protozoa)

48 h

EC5 = 114

cell multipl.

Bringmann et al. (1980)

Uronema parduzci(protozoa)

20 h

EC5 = 62

cell multipl.

Bringmann and Kühn (1980)(n): nominal concentration(e): effective concentration*: studies which are flagged as key studies** This effect value has to be considered as invalid. The authors state that in the lower range (log IC50 < 1.5 µmol/l) the accuracy of the results are questionable.

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4.2

m- / p-CRESOLTerrestrial Effects

The toxicity of m-cresol to Lactuca sativa according to the OECD-Guideline 208 was examined by
Hulzebos et al. (1993). After an exposure period of 14 days, a nominal EC50 of 96 mg/kg soil (dw)
was obtained. The authors state that during the test period, the soil concentrations of most tested
phenols dropped to < 20 % of the initial soil concentration. It is not clear whether this is also true
for m-cresol.
4.3

Other Environmental Effects

No reliable data available.
4.4

Initial Assessment for the Environment

Environmental behaviour:
According to a Mackay Level I model calculation both m- and p-cresol are mainly distributed towater (96.3 %). Experimentally determined values for the Henrys’ law constant indicate slow
volatilization from surface waters. The experimentally determined Koc values of 34.58 for m-cresoland 48.66 for p-cresol indicate a low sorption potential.
In the atmosphere, indirect photodegradation by hydroxyl radicals is expected with estimated halflives of 6.0 – 8.2 hours.
With regard to its chemical structure m-cresols and p-cresols are not expected to hydrolyse underenvironmental conditions.
Aerobic biodegradation is considered to be the major removal mechanism in the hydrosphere,leading to complete mineralization. From the available test results m-cresol and p-cresol can beconsidered as being readily biodegradable under aerobic conditions.
In surface waters and sediments half-lives in the range of some hours to a few days are expected.
Photolytical degradation in surface waters as well as anaerobic degradation in lower sediment layers
are expected to be of minor importance.
For m-cresol, a BCF of 20 was obtained in a laboratory tests on fish, indicating a low
bioaccumulation potential. Because of the similarity of the log Kow the accumulation potential of
all cresols is assumed to be low.
Environmental effects:
Ecotoxicity data are available for both m- and p-cresol. Effect values with the same tested species(fish and daphnids) indicate toxicity in the same order of magnitude, with p-cresol being slightly
more toxic.
For the acute toxicity of cresols on aquatic species reliable experimental results from tests with fish,
daphnia, algae and microorganisms are available. Long-term tests were conducted for all threetrophic levels , the most sensitive species was Daphnia magna exhibiting a NOEC of 1 mg/l.
Applying an assessment factor of 10, a PNECaqua of 0.1 mg/l for m-, p-cresols is obtained.

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5m- / p-CRESOLRECOMMENDATIONS

Environmentm-Cresol, p-cresol and m/p-cresol mixtures are currently of low priority for further work. The
substances possess 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 atvery high exposure levels, they should nevertheless be noted by chemical safety professionals andusers.
Human Health:m-Cresol, p-cresol and m/p-cresol mixtures possess properties indicating a hazard for human health.
Based on data presented by the Sponsor country, adequate risk management measures are being
applied. Countries may desire to check their own risk management measures to find out whether
there is a need for measures beyond those which are being applied already. Cresols (mixed isomersof ortho-, meta and para-) are being tested in carcinogenicity studies under the U.S. National
Toxicology Program

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6

m- / p-CRESOLREFERENCES

Altschuh, J. et al. (1999) Chemosphere 39(11), 1871-1887
Atkinson R (1994) Gas-Phase Tropospheric Chemistry of Organic Compounds. J Phys Chem Ref
Data Monograph No. 2
ATSDR (1992) Agency for Toxic Substances and Disease Registry. Toxicological profile forcresols: o-cresol, p-cresol, and m-cresol. Atlanta, GA. NTIS no. PB93-110732
Barron MG and Adelman IR (1984) Canad. J. Fish. Aquat. Sci. 41(1): 141-150
Battersby NS and Wilson V (1989) Appl. Environ. Microbiol. 55: 433-439
Bayer AG (2002a) Calculation of the environmental distribution of m-cresol according to fugacity
model Mackay level I
Bayer AG (2002b) Calculation of the environmental distribution of p-cresol according to fugacity
model Mackay level I
Bayer AG (2002c) Ready Biodegradability: Closed Bottle Test, m-Cresol
Bayer AG (2003) m-/p-Cresols - internal data on production, processing, use pattern, and workplace
exposure; unpublished
BgVV (2001) Tätigkeitsbericht 2000/2001. 3.2 Fachbereich 2. p. 22-23
BioFax (1969a) Ind. Bio-Test Lab. Inc., data sheet p-Cresol, no. 5-5/69
BioFax (1969b) Ind. Bio-Test Lab. Inc., data sheet m-Cresol, no. 3-5/69
Blum DJW and Speece RE (1991) Research Journal WPCF 63 (3): 198-207
Blume HP and Ahlsdorf B (1993) Ecotoxicol Environ Safety 26: 313-332
Bone E, Tamm A, Hill M (1976) The production of urinary phenols by gut bacteria and their
possible role in the causation of large bowler cancer. Am J Clin Nutr 29: 1448-1454
Boyd SA (1982) Soil Science 134 (5): 337-343
Bray HG, Thorpe WV, White K (1950) Metabolism of derivatives of toluene. Biochem J 46: 275278
Bringmann G, Kühn R, Winter A (1980) Z. Wasser Abwasser Forsch. 13: 170-173
Bringmann G (1978) Z Wasser Abwasser Forsch 11: 210-215
Bringmann G and Kuehn R (1976) GWF-Wasser/Abwasser 117: 410-413
Bringmann G and Kuehn R (1977a) Z Wasser Abwasser Forsch 10: 161-166
Bringmann G and Kuehn R (1980) Z Wasser Abwasser Forsch 13: 26-31
Bringmann G and Kuehn R (1982) Z Wasser Abwasser Forsch 15: 1-6
BRRC (Bushy Run Research Center/Hazleton Laboratories) (1988a) Project report 51-509,
Developmental toxicity evaluation of o-, m-, or p-cresol administered by gavage to Sprague-Dawley(CD) rats, June, 1988 (at the request of CMA) EPA/OTS0517695

44

UNEP PUBLICATIONSOECD SIDS

m- / p-CRESOLBRRC (Bushy Run Research Centre/Hazleton Laboratories) (1988b) Project Report 51-508,
Developmental toxicity evaluation of o-, m-, or p-cresol administered by gavage to New ZealandWhite rabbits, June, 1988 (at the request of CMA) EPA/OTS0517695
BRRC(Bushy Run Research Center/Hazleton Laboratories) (1989) Project Report 51-634 Twogeneration reproduction study of m-Cresol administered by gavage to Sprague-Dawley (CD) rats,
November, 1989 (at the request of CMA) EPA/OTS0529224
BRRC(Bushy Run Research Center/Hazleton Laboratories) (1989) Teresa L. Neeper-Bradley andRochelle W. Tyl., Project report 52-512, Two-generation reproduction study of p-cresol (CAS No.
106-44-5) administered by gavage to Sprague-Dawley (CD) rats.. November 13, 1989.
Unpublished data submitted by Bushy Run Research Center toThe American Chemistry Council
Cresols Panel, Washington, DC.
Bruce AM, Smith H, Watson AA (1976) Cresol poisoning. Med Sci Law 16: 171-176
Boutwell RK, Bosch DK (1959) The tumor-promoting action of phenol and related compounds formouse skin. Cancer Res 19: 413-424
Chan C-M, Lo W, Wong K-W, Chung W-F (1999) Chemosphere 39 (9), 1421-1432
Cheng M and Kligerman AD (1984) Evaluation of the genotoxicity of cresols using sisterchromatid exchange (SCE). Mutat Res 137: 51-55
Cote MA, Lyonnais J, Leblond PF (1984) Acute Heinz-body anemia due to severe cresol poisoning:
successful treatment with erythrocytapheresis. Can Med Assoc J 130: 1319-1322
Crowley JP and Margard W (1978) Summary reports on determination of mutagenic/ carcinogenic
and cytotoxic potential of four chemical compounds to Sherwin Williams Company, unpublisheddata cited in EPA IRIS data base
Danish Product Register (2002) Quantity and Use of Specific Substances. 26 February 2002
Daugherty JP and Franks H (1986) Effect of monocyclic derivatives on DNA repair in human
lymphocytes. Res Commun Chem Path Pharmac 54: 133-136
DeBruin A (1976) Metabolism of occupational agents. In: Biochem Toxicol Environm Agents: 87170, Elsevier/North-Holland Biomedical Press, Amsterdam,
DECOS (Dutch Expert Commitee on Occupational Standards) (1998) Cresols (o-, m-, p-). Healthbased recommended occupational exposure limits 1998/27, Health Council of the Netherlands, Den
Haag
DeGraeve GM, Geiger DL, Meyer JS, Bergman HL. (1980) Acute and embryo-larval toxicity ofphenolic compounds to aquatic biota. Arch. Environ. Contam. Toxicol. 9: 557-568
Deichmann WB and Keplinger ML (1981) Phenols and phenolic compounds. In: Clayton GD and
Clayton FE (Ed.) Patty's industrial hygiene and toxicology. 3rd rev ed Vol 2A, Wiley and Sons,
New York, 2597-2601
Deichmann WB and Witherup S (1944) Phenolic studies VI: The acute and comparative toxicity ofphenol and o-, m-, and p-cresols for experimental animals. J Pharmac Exp Ther 80: 233-240
Desai S, Govind R, Tabak H (1990) ACS Symp. Ser. 422: 142-156
Devillers J, Chambon P, Zakarya D, Chastrette M, Chambon R (1987) Chemosphere 16: 1149-1163
Devillers J (1988) Sci Total Environ 76: 79-83
UNEP PUBLICATIONS

45

OECD SIDS

m- / p-CRESOL

EC (1996) Technical guidance document in support of the Commission Directive 93/67/EEC onrisk assessment for new notified substances and the Commission Regulation (EC) 1488/94 on risk
assessment for existing substances. Ispra, European Chemicals Bureau
EC (1999): Council directive 1999/13/EC of 11 March 1999 on the limitation of emissions ofvolatile compounds due to the use of organic solvents in certain activities and installations, O.J. L
85/1
Emery RM (1970) Water Res 4(7): 485-491
EU (1999) Commission decision 1999/217/EC of 23 February 1999 adopting a register offlavouring substances used in or on foodstuffs drawn up in application of Regulation (EC) No.
2232/96 of the European Parliament and of the Council of 28 October 1996
Evers J, Aboudan F, Lewalter J, Renner E (1994) Hemodialysis in metacresol poisoning. Clin
Investig 72: 472
Falk-Petersen IB, Kjorsvik E, Lonning S, Moller Naley A, Sydnes LK (1985) Sarsia 70, 11-16
Freitag D, Ballhorn l, Geyer H, Korte F (1985) Environmental Hazard profile of organic chemicals.
Chemosphere 14: 1589-1616
Gaffney JS, Streit GE, Spall WD, Hall JH (1987) Environ. Sci. Technol. 21, 519-523
Geiger DL, Poirier SH, Brooke LT, Call DJ (1986) Acute Toxicities of Organic Chemicals to
Fathead Minnows (Pimephales Promelas), Vol. III. Center for Lake Superior Environmental
Studies, University of Wisconsin-Superior
Gaikwad NW, WJ Bodell (2001) Formation of DANN adducts by microsomal and peroxidase
activation of p-cresol: role of quinone methide in DANN adduct formation. Chem.-Biol. Interact.
138, 217-229
Garrett JS (1975) Association between bladder tumours and chronic exposure to cresol andcreosote. J Occup Med 17, 492
Gleason MN, Gosselin RE, Hodge HC, Smith RP (1969) Clinical toxicology of commercial
products. Acute poisoning. third ed., The Williams & Wilkins Co., Baltimore, p. 42
Grossjean D (1991) Sci Total Environ 100, 367-414. As cited in HSDB (1993)
Hamaguchi F. and Tsutsui T (2000) Assessment of genotoxicity of dental antiseptics: ability ofphenol, guaiacol, p-phenolsulfonic acid, sodium hypochlorite, p-chlorophenol, m-cresol orformaldehyde to induce unscheduled DNA syntehsis in cultured Syrian Hamster embryo cells. Jpn J
Pharmacol 83: 273-276
Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E (1983) Salmonella mutagenicity test
results for 250 chemicals. Environm Mutagen 5, Suppl. 1: 3-142
Hawthorne SB and Sievers RE (1984): Environ Sci Technol 18, 483-490.
Hawthorne SB et al. (1992) Environ Sci Technol 26, 2251-62
Hazleton Laboratories America Inc. (1988a) HLA Study No. 10002-0-431 Mutagenicity test on
meta-cresol in a mouse lymphoma mutation assay, Kensington, USA (at the request of CMA),EPA-OTS0517693
Hazleton Laboratories America Inc. (1988b) HLA Study No. 10002-0-437 Mutagenicity test on mcresol in an in-vitro cytogenetic assay measuring chromosomal aberration frequencies in Chinese
46

UNEP PUBLICATIONSOECD SIDS

m- / p-CRESOL

Hamster Ovary (CHO) cells. Kensington, USA, June 28, 1988 (at the request of CMA),EPA/OTS0517691
Hazleton Laboratories America Inc. (1988c) HLA Study No.10002-0-447 Mutagenicity test on
meta-cresol in the rat primary hepatocyte unscheduled DNA synthesis assay. Kensington, USA,
June 28, 1988 (at the request of CMA)
Hazleton Laboratories America Inc. (1988d) HLA Study No. 10002-0-451 Mutagenicity test on
meta-cresol in a mouse bone marrow cytogenetic assay. Kensington, USA, January 31, 1989 (at therequest of CMA)
Hazleton Laboratories America Inc. (1988e) HLA Study No. 10002-0-431 Mutagenicity test on
meta-cresol in a mouse lymphoma mutation assay, Kensington, USA (at the request of CMA),EPA-OTS0517693
Hazleton Laboratories America Inc. (1988f) HLA Study No. 10002-0-437 Mutagenicity test on mcresol in an in-vitro cytogenetic assay measuring chromosomal aberration frequencies in Chinese
Hamster Ovary (CHO) cells. Kensington, USA, June 28, 1988 (at the request of CMA),EPA/OTS0517691
Hazleton Laboratories America Inc. (1988g, h) Mutagenicity tests on meta-cresol and para-cresol in
the in vitro transformation of BALB/C-3T3 cells assay, June 27, 1988 (at the request of CMA),EPA/OTS 517694
Hazleton Laboratories America Inc. (1989a) Ivett JL. Dominant lethal assay in mice; p-cresol., June27, 1989 (at the request of CMA), EPA/OTS0529223
Hazleton Laboratories America Inc. (1989b) HLA Study No. 10003-0-459DL, Single acuteexposure dose selection study on para-Cresol, submitted to Chemical Manufacturers Association(Sponsor study number CRE 9.0-DL-HLA)
Hazleton Labortories America, Inc. (1989) Seranau SC. Mutagenicity test on para-cresol Drosophila
Melanogaster sex-linked recessive lethal test. February 22, 1989 (at the request of CMA)
Hodson PV, Dixon DG and Kaiser KLE (1984) Measurement of median lethal dose as a rapid
indicationofcontaminant toxicity
to fish.
Environ.
Toxicol. Chem.
3(2),243-254
Howard PH (1989) Handbook of environmental fate and exposure data for organic chemicals.
Lewis publishers Michigan, USA
Howland RM (1969) Investigations in Fish Constrol 34: 1-10, US Department of the Interior,
Bureau of Sport Fisheries and Wildlife
HSDB (1993) U.S. Department of Health and Human Services. Hazardous Substances Data Bank(HSDB online database). National Toxicology Information Program, National Library of Medicine,
Bethesda, MD
Huang JC and Gloyna EF (1968) Water Res 2: 347-366
Hulzebos EM, Adema DMM, Dirven-Van Bremen EM, Henzen L, Van Dis WA, Herbold BA,
Hoekstra JA, Baerselman R, Van Gestel CAM (1993) Phytotoxicity studies with Lactuca Sativa insoil and nutrient solution. Environ Toxicol Chem 12 (6):1079-1094
IPCS (1995) Environmental Health Criteria 168: Cresols. Geneva, World Health Organization
International Programme on Chemical Safety
UNEP PUBLICATIONS

47

OECD SIDS

m- / p-CRESOL

Jansson T, Curvall M, Hedin A, Enzell CR (1986) In vitro studies of biological effects of cigarettesmoke condensate II. Induction of sister-chromatid exchanges in human lymphocytes by weakly
acidic, semivolatile constituents. Mutation Res 169: 129-139
Kanabur VV and Sangli AB (1998) Environ Ecol 16(2): 334-336
Kelly TJ et al. (1993) Ambient Concentration Summaries for Clean Air Act Title III Hazardous Air
Pollutants. USEPA/600/R-94/090. Final Report Research Triangel Park. As cited in HSDB (1993)
Klecka GM and Landi LP (1985) Chemosphere 14 (9): 1239-1251
Kligman AM (1972) cited in: Opdyke DLJ, Fragrance raw materials monographs. p-Cresol. Food
Cosmet Toxicol 12: 389-390, 1974
Kühn R and Pattard M (1990) Water Res 24(1): 31-38
Kühn R, Pattard M, Pernak KD, Winter A (1988) Schadstoffwirkungen von Umweltchemikalien im
Daphnien-Reproduktionstest als Grundlage für die Bewertung der Umweltgefährlichkeit inaquatischen Systemen. Institut für Wasser-, Boden- und Lufthygiene des Bundesgesundheitsamtes.
Kühn R, Pattard M, Pernak KD, Winter A (1989 a) Water Res. 23(4): 501-510
Kühn R, Pattard M, Pernak KD, Winter A (1989 b) Water Res. 23(4): 495-499
Kuwata et al. (1981) Anal Chem 53: 1531-1534
Levsen K et al. (1993) Int J Environ Anal Chem 52, 87-97
Lin CH and Yang JY (1992) Chemical burn with cresol intoxication and multiple organ failure.
Burns 18: 162-166
Mandel HG (1971) Pathways of drug biotransformation: biochemical conjugations. In: LaDu BN,
Mandel HG, Way EL (Eds.) Pathways of drug biotransformation. Williams and Wilkins, Baltimore,
149-186 (cited in NTP 1991)
Mattson V, Arthur JW, walbridge CT (1976) Acute Toxicity of Selected Organic Compounds toFathead Minnows. US-EPA, Report No.EPA-600/3-76-097
Mellon Inst Ind Res (1949) Special report on the acute toxicity of m-cresol. Univ. Pittsburgh, USA,
EPA/OTS 0517523
Microbiological Associates Inc., Mulligan LT (1988a) Subchronic toxicity of meta-cresol inSprague-Dawley rats, MBA Chemical No: 24, Study No. 5221.07, Final Report, Bethesda, USA (atthe request of Research Triangle Instiute: Dennis Dietz), NTIS Report No. PB88-195284
Microbiological Associates Inc., Mulligan LT (1988b) Subchronic toxicity of para-cresol inSprague-Dawley rats, MBA Chemical No: 25, Study No. 5221.08, Final Report, Bethesda, USA (atthe request of Research Triangle Instiute: Dennis Dietz), NTIS Report No. PB88-195292
Miller SL et al. (1998) : Exposure to Toxic Air Contaminants in Environmental Tobacco Smoke :An Assessment for California Based on Personal Monitoring Data. J. Exposure Analysis Environm.
Epidemiol. 8, 287-311
Minami M, Katsumata M, Tomoda A (1990) Methemoglobinemia with oxidized hemoglobins andmodified hemoglobins found in bloods of workers handling aromatic compounds and in those of aman who drank cresol solution. Biomed Biochim Acta 49: 327-333
Needham et al.(1984) Analytical Letters, 17(B14), 1555-1565
48

UNEP PUBLICATIONSOECD SIDS

m- / p-CRESOL

Nobel W, Mayer T, Kohler A (1983) Z. Wasser Abwasser Forsch. 16(3): 87-90
NTP (1991) Toxicity studies of cresols (CAS Nos 95-48-7, 108-39-4, 106-44-5) in F344/N rats and
B6C3F1 mice (feed studies), NTP-Tox 9. Research Triangle Park, NC, U.S. Department of Healthand Human Services, Public Health Service, National Institutes of Health, National Toxicology
Program, Report Date: February 1991
OECD (1998) Screening Information Data Set (SIDS) for High Production Volume Chemicals. Vol.
5, Part I. Organisation for Economic Co-operation and Development, Paris, October 1998
Pereima V (1975) Inhalational effect of cresol isomers at low concentrations and means for
improving detoxication processes in experiments on white rats. Lvov University, pp 86-90(Dissertation)
Pereima V (1977) Cytotoxicity of cresol isomers in aerosol in subtoxic concentrations. Vrachebnoe
Delo 5: 126-130
Pitter P (1976) Determination of biological degradability of organic substances. Water Research 10:231-235
Pool BL and Lin PZ (1982) Mutagenicity testing on the Salmonella typhimurium assay of phenolic
compounds and phenolic fractions obtained from smokehouse smoke condensates. Food Chem
Toxicol 20: 383-391
Pulich WM Jr, Winters K, Van Baalen C (1974) The effect of No. 2 fuel oil and two crude oils on
the growth and photosynthesis of microalgae. Mar. Biol. 28, 87-94
Renwick AG, Thakrar A, Lawrie CA, George CF (1988) Microbial amino acid metabolites andbladder cancer: No evidence of promoting activity in man. Hum Toxicol 7: 267-272
Roberts MS, Anderson RA, Swarbrick J (1977) Permeability of human epidermis to the phenolic
compounds. J Pharm Pharmacol 29: 677-689
Roempp (1999). Roempp Lexikon Chemie, 10th edition. G. Thieme Verlag, Stuttgart.
Rote Liste (2002) Win 2002/II, Version 3.0, Arzneimittelverzeichnis für Deutschland(einschliesslich EU-Zulassungen) der Verbände der pharmazeutischen Industrie BPI, VFA, BAH
und Deutscher Generikaverband e.V. für Microsoft Windows
RTI (Reseach Triangle Institute) (1992) Final report on the reproductive toxicity of meta-/paracresol in CD-1 Swiss Mice, prepared for the National Toxicology Program, Research Triangle Park,
NC, PB 92-191741
Ruebelt C, Dietz F, Kickuth R, Koppe P, Kunte H, Peschel G, Sonneborn M (1982) Schadstoffe im
Wasser. Band II, Phenole. Boldt Verlag, Boppard, S. 101-115
Saarikoski J and Viluksela M (1982) Ecotox Environ Safety 6: 501-512
Sangli AB, Kanabur VV (2000) Acute toxicity of cresol and chlorophenol to a freshwater Gambusia
affinis and their effects on oxygen uptake. Journal of Environmental Biology 21 (3): 215-217
SCCNFP (2000) The Scientific Committee on Cosmetic Products an Non-Food Products Intended
for Consumers. The 1st Update of the Inventory of Ingredients employed in Cosmetic Products.
Section II: Perfume and Aromatic Raw Materials, 24 October 2000.
Schaltenbrand W.E and Coburn SP (1985) Determination of phenol and p-cresol in urine. Clin
Chem 31: 2042-2043
UNEP PUBLICATIONS

49

OECD SIDS

m- / p-CRESOL

Scheline RR (1973) Metabolism of foreign compounds by gastrointestinal microorganisms.
Pharmacological Reviews 25: 451-523
Schultz TW, Bryant SE, Kissel TS (1996) Bull. Environ. Contam. Toxicol. 56: 129-134
Scully FE and Hoigne J (1987) Chemosphere 16 (4): 681-694
Semadeni M, Stocker DW, Kerr JA (1995) Int. J. Chem. Kinet. 27: 287-304
Shah JJ and Singh HB (1988) Environ Sci Technol 22, 1381-88
Sharp DW (1978) The sensitization potential of some perfume ingredients tested using a modified
Draize procedure. Toxicology 9: 261-271
Shelley WB (1974) p-Cresol: cause of ink-induced hair depigmentation in mice. Br J Dermatol 90,
169-174
Shelton DR and Tiedje JM (1981) Development of test for determining anaerobic biodegradation
potential. NTIS report: PB 84-166495, Springfield
Shelton DR, Tiedje JM (1984) Appl. Environ. Microbiol. 47: 850-857
Solski A and Piontek M (1987) Pol Arch Hydrobiol 34 (4): 543-550
Srour R.(2000, 2001) Aromatic intermediates and derivatives; collection of sheets, Paris, 2000,
2001
Swedish Product Register (2002) Communication to BUA
Swiss Product Register (2002) Communication to BUAThomas RG (1990) Volatilization from water. In: Handbook of chemical property estimation
methods, Lyman WJ, Reehl WF, Rosenblatt DH (Eds.), McGraw-Hill Book Company, New York:
15-16
Thomas WH et al. (1980) Mar Environ Res 4: 203-215
Thompson DC, Perera K, London R (1996) Studies on the mechanism of hepatotoxicity of 4methylphenol (p-cresol): effects of deuterium labeling and ring substitution. Chem-Biol Interact
101: 1-11
Tomlinson TG, Boon, AG, Trotman CNA (1966) J. Appl. Bact. 29 (2), 266-291
Tremp J et al. (1988) ACS Div Environ chem 192nd Natl Mtg 26 : 142-143. As cited in HSDB
(1993)TRGS 900 (2002) Technische Regeln für Gefahrstoffe 900: Limit values relating to air in theworkplace, BarbBl. 3, 2002
TRL (Toxicity Research Laboratories) (1986) TRL-Study #032-009: Subchronic neurotoxicity
study in rats of ortho-, meta- and para-Cresol, November 18, 1986 (at the request of Research
Triangle Instiute: Dietz DD) (Summary)
Ullmann (2002) Ullmann’s encyclopedia of industrial chemistry on CD-ROM, 6th ed., Wiley-VCH
UNEP (United Nations Environmental Program) (1998) Chemical Screening Information DataSets(SIDS) for High Volume Chemicals: o-Cresol, Vol. 5/I
Van Veld PA and Spain JC (1983) Chemosphere 12 (9/10): 1291-1305
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Vernot EH, MacEwen JD, Haun CC, Kinkead ER (1977) Acute toxicity and skin corrosion data forsome organic and inorganic compunds and aqueous solutions. Toxicol Appl Pharmacol 42, 417-423
Wellens HZ (1982) Wasser Abwasser Forsch 15: 49-52
Wellens HZ (1990) Wasser Abwasser Forsch 23: 85-98
Yoshioka Y, Ose Y, and Sato T (1985) Testing for the toxicity of Chemicals with Tetrahymena
pyriformis. Oxyge. Sci. Total Environ. 43(1-2), 149-157
Younger Laboratory (1974) Skin irritation in albino rabbits after application of o-, m- and p-Cresol(at the request of Productol Chemical Company, Whittler, California), EPA/OTS0517499

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m- / p-CRESOLANNEX: CATEGORY JUSTIFICATION
Identity:
Chemical name:m-Cresolp-Cresolm/p-Cresol mixtures

Since o-cresol was assessed earlier within the OECD HPV program, it is not included here (UNEP(United Nations Environmental Program) (1998), Chemical Screening Information Data Sets
(SIDS) for High Volume Chemicals: o-Cresol, Vol. 5/I)
Structural Formula:

OH

OH

CH3
CH3
m-Cresolp-Cresol

Molecular Formula:C 7 H 8O

Molecular weight:

108.14 g/mol

m-Cresol, p-cresol and mixtures of both isomers are considered as a category because of theirsimilarity in physico-chemical properties, environmental fate, ecotoxicity and toxicity. Bothisomers as well as their mixture are products of technical importance. m-Cresol, p-cresol andmixtures of both isomers are produced > 1000 t/y.
The 3 cresol products of technical importance considered here, are:Substance

Synonyms

CAS-No.

Composition

m-Cresol

3-Methylphenol

108-39-4

Purity > 99 %p-Cresol

4-Methylphenol

106-44-5

Purity approx. 99.9 %15831-10-4

60 - 75 % m-Cresol,
25 - 40 % p-Cresolm/p-Cresol
mixtures

Category Justification
Environment
Of particular importance to environmental effects are the values for partition coefficient (log Kow),
vapour pressure and water solubility.

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Available Physico-Chemical Data for Cresols:
Substance

m-Cresolp-Cresolm/p-Cresol

Vapour pressure (25°C)

0.147 hPa

0.147 hPa

Log Kow

1.96

1.94

1.94 -1.96

Water solubility (25°C)

22.7 g/l

21.5 g/l

24.4 g/l

Dissociation constant pKa

10.09

10.26

Vapour pressure and log Kow were determined for both isomers, the water solubility for bothisomers and the m/p-cresol mixture. The values are nearly identical for the pure isomers, so theisomer mixture can be assessed as well.
Cresols are weak acids. The pKa values of 10.09 and 10.26 resp. indicate that at environmentally
relevant pH values (5 - 9) both substance are largely non-dissociated.
For the assessment of the removal in biological treatment plants and degradation in environmental
compartments, results from biodegradation tests are crucial.
Available Data on Ready Biodegradability
MethodDurationm-CresolOECD 301 D

28 d

65 - 90 %OECD 301 C

40 d

80 - 95 %p-Cresol

Reference
Bayer AG (1988)

80 - 95 %Desai et al. (1990)

The OECD 301 D test reveals that m-cresol is readily biodegradable. As demanded by the OECD
guideline, the oxygen consumption was above 60 % after 28 days and the 10d window was fulfilled.
In a test comparable to OECD 301 C test biodegradation in the range of 80 – 95 % for bothcompounds occurred. The oxygen uptake curves are not reported. However, the authors state that all
test compounds revealed the lag phase, biodegradation phase and the plateau region within a periodof 10 days. Therefore, it can be concluded from this test that m- and p-cresol are readily
biodegradable. In addition, the rate constants for both m- and p-cresol were determined and foundto be similar.
Available Ecotoxicity Data
For the acute toxicity of cresols on aquatic species a large number of experimental results from tests
with fish, daphnids and algae are available. Long-term tests were conducted with fish, algae andinvertebrates.
In the following table only those tests are reported where both isomers have been tested in parallel.

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Toxicity of m - and p-cresol in Short-term Tests:
Species

ExposureperiodEffects [mg/l]
m-Cresolp-Cresol

96 hLC50 = 55.9 (e)LC50 = 28.6 (e)96 hLC50 = 8.9 (e)LC50 = 7.9 (e)96 hLC50 = 8.6 (n)LC50 = 7.4 (n)Leuciscus idus

48 h

LC50 = 17 (n)LC50 = 11 (n)Salmo trutta

96 hLC50 = 8.4 (n)LC50 = 4.4 (n)Salvelinus fontinalis

96 hLC50 = 7.6 (n)LC50 = 5.8 (n)Daphnia magna

24 hEC50 =19.2 (n)EC50 =12.4 (n)Daphnia pulicaria

48 h

EC50 > 99.5 (e)EC50 = 22.7 (e)Pimephales promelas
Oncorhynchus mykiss

Chlorella pyrenoidosa(n): nominal concentration

72 hEC50 = 50 - 250 (n)(e): effective concentration

EC50 = 100 - 250 (n)Effect values obtained from tests on both m- and p-cresol indicate a similar toxicity of both isomers,
with p-cresol being slightly more toxic.
For long-term tests the toxicity cannot be compared directly, as no test performed with both isomers
are available. However, from the similarity in acute toxicity testing, it can be expected that the longterm toxicity of both isomers is similar as well.
For the isomeric mixture m/p-cresol no ecotoxicity data are available. However, it is expected thatthe toxicity of the isomeric mixture is covered by the data for m- and p-cresol.
Available Toxicity Data (Human Health)
The available data indicate a very similar pattern of toxicity of m-cresol, p-cresol and of the m/pcresol mixtures:
The following data were identified:
Substance

m-Cresolp-Cresol

Cas-No.

108-39-4

106-44-5

m/p-Cresol mixtures

Acute toxicity

oral
dermalinhalation

√/+
√/+
√/+

√/+
√/+
√/+

Irritation

skin
eye

√/+
√/+

√/+
√/+

√/+

√/-

√/-

√/-

Repeated dose toxicity

√/+

√/+

√/+

Genetic toxicity

√/+
√/+

√/+
√/+

√/+
√/+

Carcinogenicity

X

X

Effect on fertility
Developmental toxicity

√/+
√/+

√/+
√/+

Sensitization

√/+

54

in vitroin vivo

Adequate data available

UNEP PUBLICATIONS√/+OECD SIDS

m- / p-CRESOL√

information available*

evaluation based on human experienceX

Testing being performed (o-/m-/p- isomer mixture)

All cresol isomers are well absorbed via all main exposure routes. The main metabolic pathway ishydroxylation of the benzene ring. p-Cresol can also be oxidized to hydroxybenzoic acid and, atleast in vitro, to a reactive quinone methide. For m- and p-cresol, elimination occurs mainly as
glucuronide and/or sulfate via urine, minor amounts via faeces.
The available acute toxicity data of the two isomers indicate similar toxicity profiles after oral
exposure, and a lesser toxicity of m-cresol in experiments with dermal exposure. m-Cresol and pcresol are corrosive substances.
There is no indication of a sensitizing effect of p-cresol from a limited guinea pig study and alimited human study. However, hypersensitivity reactions of some individuals to cresol (isomer
unspecified) have been mentioned in the literature.
For both isomers, as well as for the mixture of the two the NOAELs in 28- and 90-d feeding studies
are ≥ 50 mg/kg bw/day in rodents. At higher doses, there were indications of a transient impairmentof liver function and a dose dependant increase in liver weight was observed for m-, p- and the
mixture of cresols, but without histopathological correlate. Increases in kidney weight wereobserved with p-cresol and at higher doses with the m/p-cresol mixture.
p-Cresol exerted some clastogenic activity in vitro, but this activity was not reproduced in vivo. All
isomers were consistently tested negative in vivo.
There is no adequate data available to assess the carcinogenic potential of m- and p-cresol. Limited
studies gave an indication of a tumour promoting activity of m- and p-cresol. Carcinogenicity
studies in two species with the o-/m-/p-isomer mixture are currently performed within the U.S.
National Toxicology Program.
None of the isomers, and also not the mixture, was a reproductive toxicant. Mild developmental
toxicity was only seen at maternally toxic doses of p-cresol; there was no indication ofdevelopmental effects with m-cresol. Hence, slight developmental toxicity at maternally toxic doses
may also occur with the isomer mixture.
Based on the similarities in the results of studies on m-and p-cresol, inclusion of m/p-cresol mixture
in this report is justified.

UNEP PUBLICATIONS

55

OECD SIDS

m-CRESOLIUCLID
Data Set
Existing Chemical
CAS No.
EINECS NameEC No.
TSCA Name
Molecular Formula

:
:
:
:
:
:

ID: 108-39-4
108-39-4
m-cresol203-577-9
Phenol, 3-methylC7H8O

Producer related part
Company
Creation date

: Bayer AG: 11.01.1994

Substance related part
Company
Creation date

: Bayer AG: 11.01.1994

56

StatusMemo::

Printing date
Revision date
Date of last update: 24.05.2004: 02.06.1994: 24.05.2004

Number of pages: 120

Chapter (profile)
Reliability (profile)
Flags (profile): Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10: Reliability: without reliability, 1, 2, 3, 4
: Flags: without flag, non confidential, WGK (DE), TA-Luft (DE), Material
Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDSX AKTUELL EG / ICCAUNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

1.0.1

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

APPLICANT AND COMPANY INFORMATION

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

Flag
31.05.2002

:

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Bayer Corporation

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date

:
:
:
:

cooperating company
Concord Chemical Company

ADCHEMCO Corporation

Japan

Critical study for SIDS endpoint

American Chemistry Council Cresol Panel

United States

100 Bayer Road
PA 15205-9741 Pittsburgh
United States

UNEP PUBLICATIONS

57

OECD SIDS
1. GENERAL INFORMATION

58

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Dakota Gasification Company

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Honshu Chemical Industry Company, Inc.

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
LaPorte (formerly Inspec Fine Chemicals)

United States

United States

Japan

United States

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Merisol (Merichem-Sasol USA LLC)

Flag
01.08.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Mitsui Chemicals, Inc.

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Nippon Steel Chemical Company, Ltd.

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
Street:::::cooperating company
PMC Specialties Group, Inc.

United States

United States

Japan

UNEP PUBLICATIONS

59

OECD SIDS
1. GENERAL INFORMATION

60

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Town
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumiken Chemical Company, Ltd.

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumitomo Chemical Americas, Inc.

Flag
27.07.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumitomo Chemical Company, Ltd.

United States

United States

United States

Japan

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION
Flag
27.07.2001:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Critical study for SIDS endpoint

1.0.2

LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR

1.0.3

IDENTITY OF RECIPIENTS

1.0.4

DETAILS ON CATEGORY/TEMPLATE

1.1.0

SUBSTANCE IDENTIFICATION

1.1.1

GENERAL SUBSTANCE INFORMATION

Purity type
Substance typePhysical status
PurityColour
Odour

:
:
:
:
:
:

Flag
07.01.2003:

Organic
Liquid> 99

Critical study for SIDS endpoint
(1)

1.1.2

SPECTRA

1.2

SYNONYMS AND TRADENAMES

1-HYDROXY-3-METHYLBENZOL
Flag:

Critical study for SIDS endpoint

1-OXY-3-METHYLBENZOL
Flag:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint

3-HYDROXYTOLUOL
Flag
3-KRESOL
Flag
3-METHYLPHENOLFlag
M-HYDROXYTOLUOLUNEP PUBLICATIONS

61

OECD SIDS
1. GENERAL INFORMATION
Flag

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint:

Critical study for SIDS endpoint

M-KRESOLFlag
M-KRESYLSAEURE
Flag
M-OXYTOLUOLFlag
M-TOLYLALKOHOL
Flag
PHENOL, 3-METHYL
Flag
1.3

IMPURITIES

PurityCAS-NoEC-No
EINECS-Name
Molecular formula
Value

:
:
:
:
:
:

106-44-5
203-398-6
p-cresol< 1 % w/w

15.01.2003
PurityCAS-NoEC-No
EINECS-Name
Molecular formula
Value

(1)
:
:
:
:
:
:

7732-18-5
231-791-2
water
< .05

20.01.2003
1.4

ADDITIVES

1.5

TOTAL QUANTITY

62

(1)

Quantity:- tonnes produced in

Remark
Flag
28.05.2002::

28,500 t in 2000, estimated world capacity
Critical study for SIDS endpoint

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION
1.6.1

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

LABELLING

LabellingSpecific limits
Symbols
Nota
R-Phrases

:
:
:
:
:

S-Phrases:

RemarkFlag::

19. Adaption, EC-Index-No. 604-004-00-9
Critical study for SIDS endpoint

Classified
Class of danger
R-Phrases
Specific limits

:
:
:
:

as in Directive 67/548/EEC
toxic(24/25) Toxic in contact with skin and if swallowedFlag
16.11.2000:

Critical study for SIDS endpoint

Classified
Class of danger
R-Phrases
Specific limits

:
:
:
:

as in Directive 67/548/EEC
corrosive(34) Causes burns

Flag
16.11.2000:

Critical study for SIDS endpoint

Type of use
Category::type
Use in closed systemFlag
11.09.2000:

Critical study for SIDS endpoint

Type of use
Category::

industrial
Chemical industry: used in synthesisFlag
16.11.2000:

Critical study for SIDS endpoint

Type of use
Category::useIntermediates

1.6.2

as in Directive 67/548/EEC
T, , ,,,(24/25) Toxic in contact with skin and if swallowed(34) Causes burns(36/37/39) Wear suitable protective clothing, gloves and eye/faceprotection(45) In case of accident or if you feel unwell, seek medical advice
immediately (show the label where possible)

CLASSIFICATION

1.6.3

PACKAGING

1.7

USE PATTERNUNEP PUBLICATIONS

63

OECD SIDS
1. GENERAL INFORMATION

Flag
11.09.2000:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Critical study for SIDS endpoint

1.7.1

DETAILED USE PATTERN

1.7.2

METHODS OF MANUFACTURE

1.8

REGULATORY MEASURES

1.8.1

OCCUPATIONAL EXPOSURE LIMIT VALUES

Type of limit: MAK (DE)
Limit value: 22 mg/m3
Short term exposure limit value
Limit value: 22 mg/m3
Time schedule:
Frequency: times
Remark:all isomeres (CAS-Nr. 1319-77-3)
danger of cutaneous absorption
TRGS 900 (DE)
Critical study for SIDS endpoint

SourceFlag
24.05.2002::

Type of limit
Limit value::

MAK (DE)

Remark:danger of cutaneous absorption
MAK list, canc. category 3A

27.05.2002(2)

Type of limit
Limit value::

TLV (US)other: 5 ppm (= 22 mg/m³)

Remark:Flag
19.09.2000

:

(TWA)
all isomers
danger of cutaneous absorption
Critical study for SIDS endpoint

1.8.2

ACCEPTABLE RESIDUES LEVELS

1.8.3

WATER POLLUTIONClassified byLabelled byClass of danger

64

:
:
:

KBwS (DE)KBwS (DE)
2 (water polluting)

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION
1.8.4

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

MAJOR ACCIDENT HAZARDS

Legislation
Substance listed
No. in Seveso directive:::

Stoerfallverordnung (DE)yesRemark
17.07.2001:

App. I, No. 2

:
:
:
:

TA-Luft (DE)1.8.5

AIR POLLUTIONClassified byLabelled byNumberClass of danger

3.1.7 (organic substances)
I

1.8.6

LISTINGS E.G. CHEMICAL INVENTORIES

1.9.1

DEGRADATION/TRANSFORMATION PRODUCTS

1.9.2

COMPONENTS

1.10

SOURCE OF EXPOSURE

1.11

ADDITIONAL REMARKS

1.12

LAST LITERATURE SEARCH

Type of search
Chapters covered
Date of search:::Internal and External

Remark

:Toxicology: November 2002
Environmental aspects and ecotoxicology: January 2002
CAS number search in external and internal databases, e.g. HSDB, Aquire,
Biosis, Embase, Toxline, Scisearch.

22.01.2003
1.13

REVIEWS

UNEP PUBLICATIONS

65OECD SIDS
2. PHYSICO-CHEMICAL DATA

2.1

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

MELTING POINT

Value
Sublimation
MethodYear
GLP
Test substance

:
:
:
:
:
:

Remark
Flag
10.05.2004::

SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint

Value
Sublimation
MethodYear
GLP
Test substance

:
:
:
:
:
:

11.5 °C

11.8 °C
other: no data available
no dataother TS: m-cresol, no purity reported

other: no data available
no dataother TS: m-cresol, purity > 95 % according to product specification on
MSDS of Bayer

10.05.2004
Value
Sublimation
MethodYear
GLP
Test substance(3) (4)
:
:
:
:
:
:

11 - 12 °C
other: no data available
no dataother TS: m-cresol, no purity reported

10.05.2004
Value
Sublimation
MethodYear
GLP
Test substance

(5)
:
:
:
:
:
:

12 °C
other: no data available
no dataother TS: m-cresol, no purity reported

10.05.2004
Value
Sublimation
MethodYear
GLP
Test substance(6) (7)
:
:
:
:
:
:

12.2 °C
other: no data available
no dataother TS: m-cresol, no purity reported

10.05.2004
2.2

BOILING POINT

Value
Decomposition
Method
Year

66

(8)

:
:
:
:

202 °C atother: no data available
1996

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
GLP
Test substance::

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

no dataother TS: m-cresol, no purity reported

10.05.2004(5) (7)

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

Remark
Flag
10.05.2004

:
:

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

202.2 °C at 1013 hPaother: no data available
no dataother TS: m-cresol, no purity reported
SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint(8) (9)203 °C atother: no data available
1987
no dataother TS: m-cresol, no purity reported

10.05.2004
2.3

(6)

DENSITY

Type
Value
MethodYear
GLP
Test substance

:
:
:
:
:
:

ca. 1.03 g/cm³ at 20 °C
no dataother TS: m-cresol, purity > 95 % according to product specification on
MSDS

10.05.2004

(3)

Type
Value
MethodYear
GLP
Test substance

:
:
:
:
:
:

density
1.0336 g/cm³ at 20 °C
no dataother TS: m-cresol, no purity reported

Flag
10.05.2004:

Critical study for SIDS endpoint

Type
Value
MethodYear
GLP
Test substance

:
:
:
:
:
:

(8)
density
1.034 g/cm³ at °C
1987
no dataother TS: m-cresol, no purity reported

10.05.2004(9) (6) (5)UNEP PUBLICATIONS

67OECD SIDS
2. PHYSICO-CHEMICAL DATA
2.3.1

GRANULOMETRY

2.4

VAPOUR PRESSURE

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004.13 hPa at 20 °C

no dataother TS: m-cresol, purity > 95 % according to product specification on
MSDS of Bayer

10.05.2004(8) (3)

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

.147 hPa at 25 °C
other (measured)
1989
no dataother TS: m-cresol, no purity reported

Remark
Flag
10.05.2004::

SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

(10)
.28 hPa at 30 °C

no dataother TS: m-cresol, no purity reported

10.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

1.3 hPa at 50 °C

no dataother TS: m-cresol, purity > 95 % according to product specification on
MSDS of Bayer

10.05.2004
Value
Decomposition
MethodYear
GLP
Test substance(8) (3)
:
:
:
:
:
:

1.33 hPa at 52 °C

no dataother TS: m-cresol, no purity reported

10.05.2004
2.5

PARTITION COEFFICIENT

Partition coefficient

68

(6)

:

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
Log pow
pH value
MethodYear
GLP
Test substance

:
:
:
:
:
:

Remark
Flag
10.05.2004::

Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

1.96 at °C
other (measured)
no dataother TS: m-cresol, no purity reported
expertimental data, SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint(11)
1.96 at °C

no dataother TS: m-cresol, no purity reported

10.05.2004
Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

(7)
:
:
:
:
:
:
:

2.01 at °C

no dataother TS: m-cresol, no purity reported

10.05.2004
2.6.1

(7)

SOLUBILITY IN DIFFERENT MEDIA

Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
PKa
Description
StableDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Water
22.7 g/l at 25 °C

Remark
Flag
10.05.2004::

SRC (EPI Suite v 3.10) recommended value (measured)
Critical study for SIDS endpoint

Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.

:
:
:
:
:
:

at °C
at 25 °C

other: measured
1992
no dataother TS: m-cresol, no purity reported

(12)
Water
23.5 g/l at 20 °C
at °C

UNEP PUBLICATIONS

69

OECD SIDS
2. PHYSICO-CHEMICAL DATA
PKa
Description
Stable:::m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

at 25 °C

10.05.2004
Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
Stable

(7)
:
:
:
:
:
:
:
:
:

Water
24 g/l at 25 °C
5
20 g/l at °C
at 25 °C

07.05.2004
Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
Stable

(3)
:
:
:
:
:
:
:
:
:

Water
58 g/l at 100 °C
at °C
at 25 °C

10.05.2004
2.6.2

SURFACE TENSION

2.7

FLASH POINT

Value
Type
MethodYear
GLP
Test substance

(7)

:
:
:
:
:
:

86 °C
closed cup
other: DIN 51758
other TS: m-cresol, no purity reported

07.05.2004
2.8

70(6) (5)

AUTO FLAMMABILITY

Value
MethodYear
GLP
Test substance

:
:
:
:
:

575 °C atother: DIN 51794
2000
no dataother TS: m-cresol, no purity reported

Remark
10.05.2004:

autoignition temperature

Value

:

(13)
558 °C at

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

MethodYear
GLP
Test substance

:
:
:
:

other: no data available
1987
no dataother TS: m-cresol, no purity reported

Remark
10.05.2004:

autoignition temperature
(6)

2.9

FLAMMABILITY

2.10

EXPLOSIVE PROPERTIES

Remark20.11.2000:

Explosive limits: lower: 1.0 % by volume (45 g/m3)
(3)

2.11

OXIDIZING PROPERTIES

2.12

DISSOCIATION CONSTANT

Acid-base constantMethodYear
GLP
Test substance

:
:
:
:
:

10.1
other: calculation
2002

10.05.2004(14)

Acid-base constantMethodYear
GLP
Test substance

:
:
:
:
:

10.09
other: measured and calculated
1968
noother TS: m-cresol, no purity reported

Method:RemarkResultFlag
10.05.2004:::

Experimental data for cresols were taken from Kortuem G, Vogel W, andAndrussow K (1961) Dissociation Constants of Organic Acids in Aqueous
Solution. Butterworths, London
For experimental data: Secondary literature
Calculated result is pk = 10.1
Critical study for SIDS endpoint(15)

Acid-base constantMethodYear
GLP
Test substance

:
:
:
:
:

10.49
other: measured
1971
noother TS: m-cresol, no purity reported, but substance purified by distillation
under reduced pressure

Method:Remark
10.05.2004:

Measured according to Bordwell FG and BD Cooper (1952) J. Am. Chem.
Soc. 74, 1058
in 20 % water-ethanol (v/v) at 20 °C(16)

UNEP PUBLICATIONS

71

OECD SIDS
2. PHYSICO-CHEMICAL DATA

2.13

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

VISCOSITY

Test type
Test procedure

:
:

other

Remark18.10.2001:.0169 Pa*s at 20 degrees C

2.14

(3)

ADDITIONAL REMARKS

Remark:Maximum vapor concentration:
20 degrees Celsius: 0.58 g/m3
30 degrees Celsius: 1.2 g/m3
50 degrees Celsius: 5.2 g/m3

18.10.2001
Remark(8):

Refraction index (nD):
1.5438 at 20 degrees Celsius

18.10.2001(9)

Remark18.10.2001:

Remark:Refraction index (nD): 1.5398 at 20 degrees C(5)
I. Threshold odor concentration in water: 0.800 ppm
II. Threshold taste concentration in water: 0.002 ppm

18.10.2001

72

(17)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

3.1.1

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

PHOTODEGRADATION

Type:Light source:
Light spectrum:
Relative intensity:
INDIRECT PHOTOLYSIS
Sensitizer:
Conc. of sensitizer:
Rate constant:Degradation:
Deg. product:
Method
:
Year
:
GLP
:
Test substance:
Remark:Reliability:

Flag
10.05.2004:

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition:

Reliability:

Flag
11.05.2004:

Type
Light source
Light spectrum
Relative intensity
Deg. product

:
:
:
:
:

air
nm
based on intensity of sunlightOH
500000 molecule/cm³.00000000000873 cm³/(molecule*sec)
50 % after 6 hour(s)other (calculated): with SRC-AOPWIN, v1.90
2003

The calculated half-life is based on a mean OH radical concentration of
0.5E+6 OH radicals/cm3 given during the 24 hours/day as suggested in the
EU-Technical Guidance Document(2) valid with restrictions
Generally accepted calculation method
Critical study for SIDS endpoint
(18)
air
nm
based on intensity of sunlightother (measured)
1995
no dataother TS: m-cresol, purity > 99 %Determination of the temperature-dependency of the
OH-radical reaction under simulated tropospheric conditions
With a OH radical concentration of 1 000 000 molec cm-3 anda temperature of 299 K, the half-life is 3.8 h
kOH = 5.17 x 10E-12 exp[(686+-231)/T] cm3 molec.-1 s-1 for atemperature range of 299-373 K
test substance concentration 0.05-5 ppm
reference compound (o-cresol) 0.05-2.3 ppm
radical source methylnitrite 1.5-11 ppm together with NOx
2-70 ppm(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions
Critical study for SIDS endpoint
(19)
air
nm
based on intensity of sunlight

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

MethodYear
GLP
Test substance

:
:
:
:

other (measured): critical review
1994
no dataother TS: m-cresol, no purity reported

Remark:Result:Reliability:

Flag
11.05.2004:

With a OH radical concentration of 1 000 000 molec/cm3, thehalf-life is 3.0 h at room temperature
K[OH] = 64 [10E-12 cm3 molecule-1 s-1]
K[NO3] = 9.74[10E-12 cm3 molecule-1 s-1]
K[O3] = 1.9 [10E-19 cm3 molecule-1 s-1]
(1) valid without restriction
Critical review, evaluation of all available experimental
data
Critical study for SIDS endpoint

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:ResultReliability

:
:

(20)
air
nm
based on intensity of sunlightother (measured)
1990
no dataother TS: m-cresol, purity > 99 % (obtained from Aldrich Chemical
Company)smog chamber experiment with black light irradiation
dry air pressure 735 Torr
Temp. 296+-2 K
irradiation time 4-20 min
reference substance: propene
OH radical concentration: (1-3) x 10E7 molecule cm-3
k[OH] = 67.8 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

11.05.2004

(21)

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:Result:Reliability

:

air
nm
based on intensity of sunlightother (measured)
1987
no dataother TS: m-cresol, no purity reported
I. Smog chamber experimentII. Inkrement method
I. observed: k[OH] = 57 [10E-12 cm3 molecule-1 s-1]
II. calculated: k[OH] = 94 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

11.05.2004

74

(22)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
TypeLight source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:ResultReliability::

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

air
nm
based on intensity of sunlightother (measured)
1978
no dataother TS: m-cresol, no purity reported
smog chamber
Temp. 300 +-1 K
reference substances: n-butane, neopentane
initial concentration ca. 0.25 ppm for m-cresol
OH radical concentration: (1-4)x10E6 molecule cm-3
k[OH] = 67 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

11.05.2004(23) (24)TypeLight source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Result:Reliability

:

air
nm
based on intensity of sunlight1989
no dataother TS: m-cresol, no purity reported
K[OH] = 59 [10E-12 cm3 molecule-1 s-1]
t[1/2] = 0.3 d(4) not assignablesecondary literature

11.05.2004(25)

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result
Test condition
Reliability:::

other (measured)
1985
no dataother TS: m-cresol, no purity reported, but in most cases purity exceeded
98 %substance adsorbed onto silica gel (100 ng/g)
irradiated with UV lamp (290 nm) in a microphotoreactor
degradation 33.3% of applied amount
17 h at 15 degrees C(3) invalid
Unsuitable test system

11.05.2004
3.1.2

(26)

STABILITY IN WATER

Remark:Based on the chemical structure of the compound hydrolysis
is not expected under temperature and pH values occuring in

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3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:

Flag08.01.2003

:

3.1.3

the environment.
(2) valid with restrictions
Expert judgement
Critical study for SIDS endpoint

STABILITY IN SOIL

TypeRadiolabel
Concentration
Soil temperature
Soil humidity
Soil classification
Year
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

laboratory
°C

1990
no
other TS: m-cresol, no purity reported
Bench-scale experiments with contaminated soil.
Determination of passive evaporation and biodegradation ofcresolspassive evaporation half-life 4.2 - 4.8 weeks
biodegradation: after 4 days below detection limit
Passive evaporation: plastic petri plates (88x18 mm) placedon canopy-covered table. Temp. 10-17 degrees C, humidity 75%
Shake-flask biodegradation test: 8-25 g soil mixed with 50
ml buffer solution; shaken for 4 days
(3) invalid
Methodological deficiencies

07.05.2004

76

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

(27)

Type
Radiolabel
Concentration
Soil temperature
Soil humidity
Soil classification
Year
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

Method:Remark:laboratory
yes°Cother: see Method below
1985
noas prescribed by 1.1 - 1.4
Inocolum: subsurface microbial community of a pristine aquifer (Lula,
Okla.)
Soil: aquifer solid sample, unconsilated sand, from a depth of 4.5-5.6 m
below surface
All substances were radiolabeled.
Incubation period: 8 months
Determination of mineralization via 14CO2 evolution
The highest percent biodegradation achieved for nearly all the substancestested was 35% (e.g. anilin, which is the standard reference substance forall ready tests in OECD 301 achieved after 100 days only 15%
biodegradation).

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Result:Reliability:

15.01.2003
3.2.1

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004- After 160 days and at a concentration of 39 ng/g m-cresol in soil, ca.15%
mineralization was observed.
- The percent mineralized increased slowly and linearly with time.
- For the majority of the test compounds no adaptation period wasobserved.
(3) invalid
No standard test procedure. Test design can only be used to assess
degradation in soil of the pristine aquifer of Lula, Okla.
(28)

MONITORING DATA

Type of measurement
Media
Concentration
Method::::other: contamination at a special working place

Remark:Reliability:

Combined m-/p-cresol isomers were detected among other chemicals in
the indoor air at a shale oil wastewater facility at a concentration of 5.1 ppb.
(2) valid with restrictions
Basic data given(29)

20.01.2003
3.2.2

FIELD STUDIES

3.3.1

TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

volatility
water - air% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: measured
1999

Method:Result:

Test condition:

Thermodynamic column method of Brunner et al. 1990 applied [Brunner S,
Hornung E, Santl H, Wolff E, Pringer OG, Altschuh J, Brueggemann R(1990) Henry´s law constants for polychlorinated biphenyls: Experimental
determination and structure-property relationship. Environ Sci Technol 24,
1751 - 1754]:- Aqueous solution of the TS produced in a generator column- Solution is passed through gas liquid desorption column where it contacts
a gas stream and the partition equilibrium is reached- Gas and water are separated: water flows to the receiver dosing funnel,
the gas is conducted into an absorption vessel where the TS is absorbed inorganic solvent
Henry's law constant (25 degrees C):
H = 3.5 E-5 calculated to
H = 8.67 E-2 Pa.m3.mol-1- Temperature 25 °C- Gas phase: Nitrogen- Liquid phase: Demineralized, distilled water- Analysis: GC/ECD

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Reliability:

Flag
10.05.2004

:

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

adsorption
water - soil
% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: batch equilibrium method similar to OECD Guideline 106
1982

RemarkResult
Test condition:::

Reliability:

Flag
10.05.2004:

Koc value was determined for clay loam soil
Koc=34.58
Soil: Brookston clay loam soil, collected from top 15 cm,
air-dried, 5.10% organic matter, pH 5.7
soil/solution ratio 1:10
TS concentrations 5, 10, 20, 30, 50 mg/l, deoxygenated bypurging with N2
triplicate samples, temp. 20+-1 degrees C, incubation period 24 h(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with general accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

3.3.2(2) valid with restrictions
basic data given
Critical study for SIDS endpoint
(30)

(31)

DISTRIBUTION

Media
MethodYear:::

air - biota - sediment(s) - soil - waterCalculation according Mackay, Level I
2001

Result:

Test condition:

Calculated distribution between environmental compartments:
Air:
2.33 %
water:
96.32 %
soil:
0.69 %
bottom sediment: 0.65 %suspended sediment: 0.001 %biota:
0.0004 %data used in calculation
temperature (°C):
25molar mass (g/mol): 108.14
vapor pressure (Pa): 14.7
water solubility (g/l): 22.7
log Kow:
1.96

Reliability

78

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:

volumes in unit world (m3)air:
6 000 000 000
water:
7 000 000
soil:
45 000sediment:
21 000susp. sediment:
35
biota (fish):7(2) valid with restrictions

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Flag
11.12.2002:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

generally accepted calculation method
Critical study for SIDS endpoint
(32)

3.4

MODE OF DEGRADATION IN ACTUAL USE

3.5

BIODEGRADATION

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Control substance
Kinetic::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Result
Test condition::

Reliability:

Flag
11.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Control substance
Kinetic::

aerobic
predominantly domestic sewage.8 mg/l related to COD (Chemical Oxygen Demand)
related to= 90 (±) % after 28 day(s)7 day(s) = 45 - 80 %14 day(s) = 70 - 90 %21 day(s) = 75 - 70 %28 day(s) = 90 - 90 %%other: phenol, 0.8 mg/l
28 day(s) = 73 %%OECD Guide-line 301 D "Ready Biodegradability: Closed Bottle Test"
1988
noother TS: m-cresol pure
10-day window criteria is met
Inoculum- Type of sludge: activated sludge- Source: treatment plant, receiving domestic sewage- Sampling site: Odenthal
Concentration of control substance: 0.8 mg/l
Analytical parameter: Oxygen consumption
Test temperature: 20 degrees C
Test was performed in two paralleles.
(2) valid with restrictions
Guideline Study
Critical study for SIDS endpoint(33)
aerobic
predominantly domestic sewage
2.4 mg/l related to COD (Chemical Oxygen Demand)
related to= 65 (±) % after 28 day(s)7 day(s) = 55 - 58 %14 day(s) = 58 - 66 %21 day(s) = 61 - 65 %28 day(s) = 65 - 65 %%other: phenol, 2.4 mg/l
28 day(s) = 69 %UNEP PUBLICATIONS

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m-CRESOL
ID: 108-39-4
DATE: 24.05.2004%
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Remark:Result:

Test condition:

Reliability:

11.05.2004

80

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition:

OECD Guide-line 301 D "Ready Biodegradability: Closed Bottle Test"
1988
noother TS: m-cresol pure
In two further tested concentrations (8 and 24 mg/l) the dissolved oxygen
was completely emaciated within 7 days (concentration of control
substance 8 and 24 mg/l for tests with 8 and 24 mg/l of test substance,
respectively. Also i n these control experiments, oxygen was emaciated).
Compared to the test with 0.8 mg/l the extent of degradation is lesser at 2.4
mg/l presumably due to the fact that most of the oxygen was used up at thehigh test substance concentration (10-day criteria met in only one of thetwo replicates)
Inoculum / test organism- Type of sludge: activated sludge- Source: treatment plant, receiving domestic sewage- Sampling site: Odenthal
Concentration of control substance: 2.4 mg/l
Analytical parameter: Oxygen consumption
Test temperature: 20 degrees C
Test was performed in two paralleles.
(2) valid with restrictions
Guideline Study(33)
aerobic
activated sludge, domestic
100 mg/l related to Test substance
related to
80 - 95 (±) % after 40 day(s)other: comparable to OECD Guide-line 301 C
1981
noother TS: m-cresol, purity > 99 %Initial sludge concentration: 30 mg d.w./l; aniline asreference compound
Incubation period: 20-40 days; no oxygen uptake curve given;degradation of reference substance aniline >/= 60 % within 28 days
The oxygen uptake curves are not reported. However, the authors statethat all test compounds revealed the lag phase, biodegradation phase andthe plateau region within a period of 10 days, indicating that the 10-day
window criteria is met.
First order biodegradation constant (hr-1): ln k = -5.77
maximum specific substrate uptake rate per unit biomass km = 17.3 / day(Aniline 16.1, Phenol 16.9).
m-Cresol is slightly better biodegradable than phenol and aniline.
Inoculum /test organism- Type of sludge: activated- Source: municipal treatment plant, receiving predominantly domestic
sewage- Initial cell concentration: 30 mg/l
Test system- Culturing apparatus: Sapromat- Closed vessels used: yes

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3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:

Flag
11.05.2004:

Type
Inoculum
Contact time
Degradation
ResultDeg. product
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result
Test condition::

Reliability:

Flag
24.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Result
Test condition
Reliability

:
:
:

Flag
24.05.2004

:

Type

:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Initial test substance concentration: 100 mg/l
Duration of the test: 20-40 days
Test conditions- Composition of synthetic medium: OECD
- Test temperature: 25 degrees C
Reference substance: aniline 100 mg/l(2) valid with restrictions
study comparable to OECD Guideline 301 C
Critical study for SIDS endpoint(34)
aerobic
activated sludge, industrial
96 (±) % after 10 day(s)OECD Guide-line 302 B "Inherent biodegradability: Modified Zahn-Wellens
Test"
1990
no dataother TS: m-cresol, no purity reported
90% degradation during the log-phase (8 days)
Test substance conc. 50-400 mg/l DOC, 200-1000 mg/l COD
acclimatization phase 2 days(2) valid with restrictions
Guideline study; basic data given
Critical study for SIDS endpoint(35)
aerobic
activated sludge, adapted
200 mg/l related to COD (Chemical Oxygen Demand)
related to95.5 (±) % after 5 day(s)other: batch system (similar to OECD 302B "Zahn-Wellens Test")
1976
noother TS: m-cresol, no purity reported- Test compound was sole source of carbon- Inoculum density: 100 mg dry matter/l; gradual increase of TS
concentration during 20 days adaptation period- With volatile substances a test without inocculum was done todifferentiate the actual biological degradation from the losses due to mere
volatilization
Initial degradation rate: 55.0 mg COD/g/h
20 +- 3 degrees C; pH 7.2; mineral salts medium; dark; continuously stirred(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
basic data given
Critical study for SIDS endpoint(36)
anaerobic

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82

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:

anaerobic sludgeyes

Method:Result:

Test condition:

Reliability:

Flag
07.05.2004:

primary anaerobic sludge from 12 treatment plants receiving
mainly domestic wastewater were diluted to
10 % in a mineral salts medium, test substanceconcentration: 30 mg/l; secondary anaerobic sludge from 2
treatment plants diluted to 10 % in a mineral salts medium,
test substance: 50 mg/l;
incubation for 8 weeks; triplicate samples
primary sludges:
no degradation was observed in 4 sludges; degradation ranged from 55 to
103 % in 6 sludges (lag times for approx 20 % of theoretical CH4
production: 4-6 weeks); insufficient data for 2 sludges.
secondary sludge:
degradation was 92% after 4 weeks with the first sludge and
90% after 5 weeks with the second (degradation related totheoretical methane and CO2 production)
35 degrees C, due to storage of sludges before incubation, lag phase of
methanogenesis could be increased in some sludges(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint
(37)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition
Reliability

:
:

Flag
07.05.2004

:

1981
no
other TS: m-cresol, no purity reported
74-82-8 200-812-7 methane

anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
56 day(s)(±) % after
yes
1984
no
other TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
primary and secondary anaerobic sewage sludge from 9
treatment plants diluted to 10 % in a mineral salts medium;
degradation measured as gas pressure increase
data have been published by the authors as a NTIS-study (previous data
set)
in 2 different secondary sludges >75% degradationin 9 different primary sludges degradation 0-103%
incubation for 8 w at 35 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint(38)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

Flag
07.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Remark:Result:Reliability:

24.05.2004
Type
Inoculum::

Concentration:

Contact time
Degradation::

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
yes
1988
no
other TS: m-cresol, no purity reported (obtained from Aldrich Chemicals)
74-82-8 200-812-7 methane
primary anaerobic digesting sludge receiving a mixture ofdomestic and industrial wastewaterlag time 40 days, accompanied with inhibition of gas
production
net total gas production was 75 % +/- 15 % of the theoretical production(CH4+CO2)- medium 2-3 g dw/l sludge- incubation for >= 60 d at 35 degrees C- 3 replicates- sterile controls for abiotic gas production- gas production measured with hand-held pressure meter(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetailCritical study for SIDS endpoint(39)
aerobic
activated sludge, domestic.05 mg/l related to Test substance
related to35.6 (±) % after 5 day(s)other: Activated sludge test
1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given
The bioaccumulation factor of the substance and its
metabolites in activated sludge was 1100
The readily biodegradable compounds methanol and phenol were about
equally degraded like m-Cresol (41, 37 and 36 %)(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(26)
aerobic
other bacteria: acclimatized mixed culture of pentachlorophenol-degrading
bacteria
5 mg/l related to Test substance
related to
29 day(s)(±) % after

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
ResultKinetic of testsubst.

::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

ResultReliability::

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

38 hour(s) 50 %46 hour(s) 90 %%%%other: Die-away Test
1990
noother TS: gas chromatographic grade
no lag phase(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail24.05.2004

(40)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Result
Test condition::

Reliability:

aerobic
other: denitrifying cultures from unadapted mixed wastewater.39 mg/l related to Test substance
related to
100 (±) % after 17 day(s)other: measured
1989
noother TS: m-cresol, no purity reported
lag phase 3 days, completely degraded in 17 d
inoculum prepared by mixing waste water samples from 12
denitrifying treatment plants
incubated at 27 degrees C in the dark(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail24.05.2004

84

(41)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Result:

Test condition:

Reliability:

anaerobic
other: municipal sewage sludge from primary anaerobic digesters
50 mg/l related to Test substance
related to
56 day(s)100 (±) % after 49 day(s)
yes
1983
no
other TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
substance disappeared completely after 7 weeks
net CH4 production >90% of theoretical value
no transformation products observed
mineral salt medium with 10% sludge
Temperature 35 degrees C(2) valid with restrictions

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

(42)

Type
InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:

anaerobic
anaerobic sludgeyesRemarkResult::

Test condition:

Reliability:

sensitivity of acid formers and methanogenic consortia examined
at <= 400 mg/l, m-cresol was not fermented andshowed no inhibition of methane formation from degradable
substrates as compared to control cultures; 1000 mg/l
inhibited the methane production significantly (60 % ofcontrol values)
screening optimized for mechanistic study
m-cresol concentration: 200, 400 or 1000 mg/l
incubation for 6 w at 37 degrees C(4) not assignable
No standard test procedure, but in accordance with generally acceptedscientific standards; not relevant for purpose of HPV program1983
noother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane

07.05.2004

(43)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Deg. products:

Result:

Test condition:

Test substance
Reliability::

anaerobic
other: anaerobic sludge, adapted
300 mg/l related to Test substance
related toyesother: see test condition
1986
noother TS: m-cresol, no purity reported (Aldrich chemicals) (methyl 14Clabelled from Pathfinder Lab.)74-82-8 200-812-7 methane
Degradation: ca. 100 % after 9 days
Most of the methyl carbon of m-cresol (87 %) was converted to CH4.
preincubation for 2-3 months
incubation for 20 d at 37 degrees C
14C-methyl labeled(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

(44)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to1982
noother TS: m-cresol, purity > 95 %UNEP PUBLICATIONS

85

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Deg. products:

74-82-8

Method:Result:

Test condition:

Reliability:- Sludge from 2 municipal plants- Methane production monitored- HPLC to monitor disappearance of substratemineralization (related to theoretical methane and CO2
production) was 92% after 4 weeks with the first sludge and
90% after 5 weeks with the second
incubation at 35 degrees C in the dark, 10 % sludge inoculum, duplicate
tests(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(45)07.05.2004
Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Result
Test condition::

Reliability:

200-812-7 methane

anaerobic
other: anoxic lake sediment.1 mg/l related to Test substance.8 mg/l related to Test substance1982
noother TS: m-cresol, purity > 95 %
74-82-8 200-812-7 methane
after 29 weeks no significant CH4 or CO2 formation observed
incubation at 20 degrees C in the dark with occasional
shaking(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

86

(45)

Type
Inoculum::

Concentration:

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

ResultReliability::

anaerobic
other bacteria: acclimatized mixed culture of pentachlorophenol-degrading
bacteria
5 mg/l related to Test substance
related to
29 day(s)(±) % after
144 hour(s) 10 %197 hour(s) 50 %236 hour(s) 90 %%%other: Die-away Test
1990
noother TS: m-cresol, gas chromatographic grade
10-day window criteria is met(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetailUNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

12.05.2004

(40)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Result:

Test condition:

Reliability:

07.05.2004

anaerobic
other: phenol-enriched methanogenic culture
100 mg/l related to Test substance
related to
100 (±) % after 58 day(s)
yes
1988
no
other TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
lag time 42 d, complete disappearance after 58 d,
the CH4 production was 85 % of the theoretical production
nominal test concentrations m-cresol 50, 100, 150, 250, 300, 400, 500, and
700 mg/l + phenol 200 mg/l
incubation at 35 °C with continuous shaking(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(46)

Type
InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:

anaerobic
other: shallow anaerobic alluvial sand aquifer
yes

Method:Result:

Test condition:

Reliability:

2 sampling sites: 1 methanogenic, 1 sulfate-reducing
both aquifers receive leachate from a municipal landfill
lag time 43 days under sulfate-reducing and 46-90 days undermethanogenic conditions, no data for complete degradation given
test medium: 50 g [wet weight] of aquifer solids and 50 ml
of groundwater
incubation at room temperature in the dark, quadruplicates
preincubation 5 days, addition of 150 to 200 µM test
substance(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail1986
noother TS: m-cresol, no purity reported (obtained from Aldrich Chemical Co.)
74-82-8 200-812-7 methane

07.05.2004

(47)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

anaerobic
other: undefined methanogenic consortia from river sediment
54 mg/l related to Test substance
related to
yes
1989
no
other TS: m-cresol, no purity reported

UNEP PUBLICATIONS

87

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Deg. products:

74-82-8

Method:Result:

Test condition:

Reliability:

black anoxic mud collected from a river inoculated in amineral medium (10% w/v)
non-acclimated consortia: turnover rate 1.10 µmol/day/g
sediment dw (lag-phase 16 d)
acclimated consortia: turnover rate 2.37 µmol/day/g sediment dw (lagphase 0 d, based on a 24-days-incubation period), the CH4 production was
96 % of the theoretically possible yield
incubation at 28 degrees C in the dark
cultures were refed with 60 mg/l test substance every 2-4 w
for a total of 18 months(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(48)

07.05.2004
Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Result:Reliability:

200-812-7 methane

aerobic
10 mg/l related to Test substance
related to
3 day(s)26 - 100 (±) % after 3 day(s)other: cultivation method
1987
other TS: m-cresol, no purity reported in abstract
biodegradation in river water = 100 %biodegradation in sea water = 26 %The authors assume the compound to be moderately to easily
biodegradable(4) not assignable
Japanese reference with short abstract in English

24.05.2004

(49)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Result:

Test condition
Reliability::

07.05.2004
Type
Inoculum
Concentration

88

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:::

anaerobic
other: microcosm containing aquifer and ground water
18 mg/l related to Test substance
related toyes
1989
no dataother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
lag time 110 days, disappearance after approx. 225 d (values taken from agraphics)
methanogenic conditions in a microcosm(3) invalid
Insufficient documentation(50)
anaerobic
other: anoxic aquifer
300 µmol/l related to Test substance
related to

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result:Reliability:

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

1990
no dataother TS: m-cresol, no purity reported
anoxic aquifer slurries held under sulfate- andnitrate-reducing conditions
m-cresol was largely degraded in less than 6 ddegradation dependant on sulfate, inhibited by 1.0 mM
molybdate, not influenced by bromoethanesulfonic acid(4) not assignable
only abstract available

07.05.2004

(51)

3.6

BOD5, COD OR BOD5/COD RATIO

3.7

BIOACCUMULATION

Species
Exposure period
Concentration
BCF
Elimination
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Leuciscus idus melanotus (Fish, fresh water)
3 day(s) at °C.05 mg/l
20
no data

Remark:Test condition:

Reliability:

Flag
12.05.2004:

Determination of radioactivity includes possible metabolized and/or
incorporated intermediates
The authors report BCF in different tables with 17 or 20
5 fish (2-4 g) were exposed in a closed system andconcentrations determined by following radioactivity in fish and water; BCF
values related to wet weight
20-25 degrees C; pH 7; hardness 100 mg CaO/l(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetailCritical study for SIDS endpoint(26)

Species
Exposure period
Concentration
Elimination
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

other: Chlorella fusca (algae)
24 hour(s) at °C.05 mg/l
no data

Remark:In this study BCF-values of 40 and 4,900 for algae are reported without
explanation for the difference.

1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given

1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given

UNEP PUBLICATIONS

89

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Test condition
Test substance
Reliability:::

12.05.2004

It is a common observation that test substance adsorbes at the surface of
the algae. Due to the high surface / volume ratio a high BCF could beobtained.
20-25 degrees C
14C-m-cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(26)

Species
Exposure period
Concentration
BCF
Elimination
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other: Activated Sludge
5 day(s) at °C

Remark:Test substance
Reliability::

Values of bioaccumulation factors range from 10 up to 42,800.
Esters and higher alcohols are placed in the intermediate range between
3,000 and 5,000. Sodium acetat with an accumulation factor of 29,100 is
remarkable. In this ranking m-Cresol belongs to the group of compoundswith low accumulation potential.
Correlation between accumulation factors and physico-chemicalparameters was not practicable.
14C-m-cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail.
(26)

12.05.2004
3.8

1100
1985
no
other TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given

ADDITIONAL REMARKS

Memo

:

biodegradation under anaerobic conditions

Method:Result:

Test substance:

Reliability:

enrichment cultures prepared by addition of 3 g/l m-cresol
once per week
initial concentration 200-300 mg/l test substanceincubation at 37 degrees C in the dark
1st step: incorporation of CO2 giving
4-hydroxy-2-methylbenzoic acid
2nd step:
2a: dehydroxylation to 2 methylbenzoic acid (not further
metabolized) to a minor degree
2b: ring reduction, ring fission and beta-oxidation toacetate. Ring reduction appeared to be the rate-limiting
step, because no subsequent intermediates accumulated
1. U-ring-14C m-cresol
2. methyl-14C m-cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail11.12.2002

90

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(52)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY
4.1

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

ACUTE/PROLONGED TOXICITY TO FISH

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

MethodResult::

Test condition:

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

MethodResult::

Test condition:

flow throughOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
8.9
yes
other: US EPA, Methods for acute toxicity tests with fish,
macroinvertebrates, and amphibians. Nat. Environm. Res. Center, Corvallis(1974)
1980
no dataother TS: m-cresol, no purity reported
Mean length/mean weight of fish: 7.9 cm/6.0 g
sublethal effects: hyperactivity, rapid operculation,
sensitive to disturbance and gathering at the surface
DILUTION WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- Conductance: 1212.3 µmhos/cm at 25 degrees C
TEST SYSTEM- Concentrations: 1:2 dilution series- Number of replicates: 2- fish per replicate: 10- Test temperature: 14 degrees C- Dissolved oxygen: 6.5 mg/l (84.5% of saturation)- pH: 8.1
- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(53)
flow throughPimephales promelas (Fish, fresh water)
96 hour(s)
mg/l
55.9
yes
other: US EPA, Methods for acute toxicity tests with fish,
macroinvertebrates, and amphibians. Nat. Environm. Res. Center, Corvallis(1974)
1980
no dataother TS: m-cresol, no purity reported
Mean length/mean weight of fish: 4.9 cm/1.6 g
sublethal effects: loss of equilibrium, erratic swiming andtwitching at a test substance concentration of 49.8 mg/l
DILUTION WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- Conductance: 1212.3 µmhos/cm at 25 degrees C

UNEP PUBLICATIONS

91

OECD SIDS
4. ECOTOXICITY

92

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
TEST SYSTEM- Concentrations: 1:2 dilution series- Number of replicates: 2- fish per replicate: 10- Test temperature: 14 degrees C- Dissolved oxygen: 6.5 mg/l (84.5% of saturation)- pH: 8.1
- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticSalmo trutta (Fish, fresh water, marine)
96 hour(s)
mg/l
= 8.4

Method:Result:

Test condition
Reliability

:
:

Flag
07.05.2004:

10 acclimated fish exposed per concentration, 20 served ascontrols.
LC50 (6 h) = 11.0 mg/l
LC50 (24 h) = 8.6 mg/l
LC50 (48 h) = 8.4 mg/l
12 degree C, reconstituted water(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticSalvelinus fontinalis (Fish, estuary, fresh water)
96 hour(s)
mg/l
= 7.6

Method:Result:

Test condition:

10 acclimated fish exposed per concentration, 20 served ascontrols.
LC50 (6 h) = 11.4 mg/l
LC50 (24 h) = 8.2 mg/l
LC50 (48 h) = 7.6 mg/l
at concentrations of 6 to 20 mg/l, the approximate
incidences of surfacing were 20 %12 degree C, reconstituted water

(53)

no
1969
no
other TS: m-cresol, reported to be "purified grade"

(54)

no
1969
no
other TS: m-cresol, reported to be "purified grade"

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
= 8.6

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrols.
LC50 (6 h) = 14.9 mg/l
LC50 (24 h) = 10.4 mg/l
LC50 (48 h) = 10.2 mg/l
In an additional test under flow-through conditions aconcentration of 10 mg/l caused total incapacitation in 15
of 20 fish within 11.5 min, after which a recovery to ahigher level of activity was observed
12 degree C, reconstituted water(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint
(54)

no
1969
no
other TS: m-cresol, reported to be "purified grade"

07.05.2004

(54)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

semistatic
Poecilia reticulata (Fish, fresh water)
96 hour(s)
mg/l
23.12

MethodTest condition
Reliability:::

80 % of the test solution renewed at 12 h intervals
25-27 degrees Celsius, pH 7(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

no
1982
no
other TS: m-cresol, purity 99 % (BDH Chemicals)

07.05.2004
Type
Species
Exposure period
Unit
LC0

(55)
:
:
:
:
:

staticBrachydanio rerio (Fish, fresh water)
96 hour(s)mg/l11UNEP PUBLICATIONS

93

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

LC50
LC100
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Test condition
Reliability

:
:

15.9
22
no
other: Pruefrichtlinie UBA (summer 1980)1982
no dataother TS: m-cresol, no purity reported
pH 7.5 +- 0.3(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

07.05.2004

(56)

Type
Species
Exposure period
Unit
EC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticGadus morrhua (Fish, fresh water)
96 hour(s)
mg/l
> 30

Method:Result:

Test condition
Reliability::

effect endpoints: death, pathology, inhibition of cleavage
and differentiation, pigment defects
parallel test with larvae (6 days after hatching) showed
pigment effects at 10 and 30 mg/l
5 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

yes
1985
no
other TS: m-cresol, purity > 98 % as determined by GC (obtained from
Merck)

07.05.2004

(57)

Type
Species
Exposure period
Unit
LC0
LC50
LC100
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)
mg/l
10
17
22
no
other: Test procedure of the Abwasserabgabengesetzentwurf (Deutscher
Bundestag 1974)1982
noother TS: m-cresol, no purity reported(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

07.05.2004

94

(58)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

Cyprinus carpio (Fish, fresh water)
24 hour(s)
mg/l
25
1959
other TS: m-cresol, no purity reported
results from: Albersmayer and Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analytical monitoring, noinformation about the test substance. Further details are missing

07.05.2004

(59)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

Rutilus rutilus (Fish, fresh water)
24 hour(s)
mg/l
23
1959
other TS: m-cresol, no purity reported
results from: Albersmayer and Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analytical monitoring, noinformation about the test substance. Further details are missing

07.05.2004

(59)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

Tinca tinca (Fish, fresh water)
24 hour(s)
mg/l
21
1959
other TS: m-cresol, no purity reported
results from: Albersmayer and Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analytical monitoring, noinformation about the test substance. Further details are missing

07.05.2004
Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring

(59)
:
:
:
:
:
:
:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)
mg/l
6
no

UNEP PUBLICATIONS

95

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Method:Year
GLP
Test substance:::

Reliability:

other: Mann, H., Fischtest mit Goldorfen zur vergleichenden Pruefung derakuten Toxizitaet von Wasserinhaltsstoffen und Abwaessern, Praktische
Erfahrungen aus 3 Ringtesten, Z. f. Wasser- u. Abwasser-Forschung 9,103-109 (1976)1978
noother TS: m-cresol, no purity reported(4) not assignable
Secondary literature not available (Mann 1976)

07.05.2004

(17)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticother: Pleuronectes sp. (plaice)48 hour(s)mg/l
10 - 33

Test condition
Reliability::

15 degrees C(4) not assignablesecondary literature

no
1971
no
other TS: cresol, isomer not specified

07.05.2004

(60)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

Lepomis macrochirus (Fish, fresh water)
96 hour(s)mg/l
10 - 13.6
1971
other TS: m-cresol, no purity reported(4) not assignablesecondary literature

12.05.2004

(61)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

Oryzias latipes (Fish, fresh water)
48 hour(s)
mg/l
24
1986
other TS: m-cresol, no purity reported(4) not assignablesecondary literature, original source unknown

12.05.2004
Type
Species
Exposure period

96

(62)
:
:
:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Unit
LC0
LC50
LC100
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability

:

mg/l
10
17 - 19
21 - 26
noother: Bestimmung der Wirkung von Wasserinhaltsstoffen auf Fische. DEV,
L 15 (1976)1978
noother TS: m-cresol, no purity reported(4) not assignable
Insufficient documentation

07.05.2004

(63)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

other: Agonus cataphractus (poacher)48 hour(s)mg/l
10 - 33
1960
other TS: m-cresol(4) not assignablereference not available

12.05.2004
4.2

(64)

ACUTE TOXICITY TO AQUATIC INVERTEBRATESTypeSpecies
Exposure period
Unit
EC0
EC50
EC100
Analytical monitoring
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Method:Result
Test condition::

Reliability:

Flag
07.05.2004:

staticDaphnia magna (Crustacea)
24 hour(s)
mg/l
13
25
50
no
other: immobilisation test according to Bringmann & Kühn: Z. Wasser
Abwasser Forsch. 10, 162-166 (1977)1982
noother TS: m-cresol, no purity reported
Exposure of 24 h old Daphnia (strain IRCHA); 10 individuals
per concentration, duplicate samples
effect values refer to nominal test substance concentrations
20 degrees C; initial pH 8.0 +/-0.2; water saturated withoxygen; hardness: 16° d.h. (corresponding to 286 mg CaCO3/l)(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(65)

UNEP PUBLICATIONS

97

OECD SIDS
4. ECOTOXICITY

98

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Type
Species
Exposure period
Unit
LC50
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Test condition:

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
EC0
EC50
EC100
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

RemarkTest condition::

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
Method
Year

:
:
:
:
:
:
:
:

flow through
Daphnia pulicaria (Crustacea)
48 hour(s)mg/l> 99.5yesother: US EPA, Methods for acute toxicity test with fish,
macroinvertebrates, and amphibians. Nat. Environm. Res. Center, Corvallis(1974)
1980
noother TS: m-cresol, no purity reported
DILUTION AND TEST WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- pH: 8.1
- Oxygen content: 6.5 mg/l (84.5% of saturation)- Conductance: 1212.3 µhos/cm at 25 degrees C- Number of replicates, individuals per replicate: 10- Test temperature: 14 +- 1 degrees C- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(53)
Daphnia magna (Crustacea)
24 hour(s)
mg/l
1.6
8.9
25
no
1977
no
other TS: m-cresol, no purity reported
Effect endpoint: immobilisation
Hardness 16 degrees (German), pH 7.6-7.7, 20-22 degrees
Celsius(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint(66)
Daphnia magna (Crustacea)
24 hour(s)
mg/l
19.2
no
other: AFNOR (1974)
1987

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

GLP
Test substance::no dataother TS: m-cresol, purity > 95 %RemarkResult
Test condition:::

Reliability:

Effect endpoint: immobilisation
Result is reported as 24h IC50 "0.178 mmol/l" (which equals 19.2 mg/l)
Reconstituted hard water 200 mg/l CaCO3
pH 7.8-8.2
dissolved oxigen >25% of saturation(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation(67) (68)07.05.2004
Type
Species
Exposure period
Unit
LC50
Limit Test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

other: not specified
Daphnia magna (Crustacea)
48 hour(s)
mg/l
18.8
no
no dataother: according to the method described by Parkhurst et al. 19771979
noother TS: m-cresol, no purity reported

Method:Test condition:

Test substance
Reliability::

Parkhurst BR, Gehrs CW, Rubin IB (1977): Proceedings of ASTM 2nd
Annual Symposium on Aquatic Toxicology, 122-130
Daphnia magna used in the test were adults.
100-ml test beakers were filled with 80 ml test solution and 4 daphnia. All
the tests were run in triplicate.
Temperature during the test: 25 +/- 0.5°C
12h light/dark cycle
Test solution was prepared with filtered spring water (pH 7.8 alkalinity mg/l,
hardness 140 mg/l)
Control beakers were used
48h-EC50 values were obtained by PROBITThe test substance was obtained from an effluent(3) invalid
Methodological deficiencies (method description is in the other reference
from the same author). Age of daphnias used in the test is not clearlyspecified: test daphnias were "adults" (in the OECD guideline a 24h-olddaphnia is suggested); temperature during the test was 25°C (in theguideline is suggested: 18-22°C); 12 daphnia were used for each test
concentration (in the guideline 40 daphnias are suggested)(69)

07.05.2004
Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

staticDaphnia sp. (Crustacea)
48 hour(s)
mg/l
28
no

Method:test organisms were reared from daphnids collected insurface water1959
noother TS: m-cresol, no purity reported

UNEP PUBLICATIONS

99

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Remark:Test condition
Reliability::

TT = Toxicity threshold; test organisms were reared fromdaphnids collected in surface water
river water, pH 7.5(3) invalid
Experimental details missing. Study does not follow any guideline,
concentrations tested were not reported, no information about theapplication method of the test substance is given. Neither O2/pH
monitoring nor analytical monitoring were applied

12.05.2004

(70)

Type
Species
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

ResultReliability::

other aquatic mollusc: Glossosiphonia complanata

other TS: m-cresol, no purity reported
perturbation level: 1.1 mg/l(4) not assignable
Secondary literature

12.05.2004

(71)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

other aquatic arthropod: Limnoria tripunctata
100 hour(s)
mg/l
100

other TS: m-cresol(4) not assignable
Reference not available

12.05.2004
4.3

(64)

TOXICITY TO AQUATIC PLANTS E.G. ALGAE

Species
Endpoint
Exposure period
Unit
TT
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Scenedesmus quadricauda (Algae)
biomass
8 day(s)mg/l
15Method:Remark:Test condition:

incubation of 10 ml test solution (algae in defined mineralsalts medium)TT (toxic threshold concentration) refers to nominal test
substance concentration and was determined at 3 %effect compared to the control
27 degrees C; initial pH 7.0

100

noother: Cell multiplication inhibition test
1977
noother TS: m-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY
Reliability

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:(3) invalid
It is unclear whether the algae are within the exponential growth throughout
the whole exposure period of 8 days.
(72)

Species
Endpoint
Exposure period
Unit
EC0
EC50
EC100
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Chlorella pyrenoidosa (Algae)
other: chlorophyll content
72 hour(s)
mg/l
< 50
127
250
no
no

Result:

Test condition:

Reliability:

1000 mg/l: complete destruction of chlorophyll
EC50 was not reported in the study, but it can be taken from the graph
TEST ORGANISMS- Strain: Emerson strain- Test temperature: 25 +- 1 degrees C- pH: 7.0
- Photoperiod: continuous illumination
TEST PARAMETER: chlorophyll(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

07.05.2004

1968
noother TS: m-cresol, no purity reported

12.05.2004(73)

Species
Endpoint
Exposure period
Unit
TGK
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Microcystis aeruginosa (Algae, blue, cyanobacteria)
other: cell multiplication
8 day(s)mg/l
13Remark:Reliability:

TGK = Toxicity treshold, determined at 1% effect compared tocontrol(3) invalid
It is unclear whether the algae are within the exponential growth throughout
the whole exposure period of 8 days.
(74) (75)07.05.2004
Species
Endpoint
Exposure period
Unit
NOEC
LOEC
EC50
EC100

:
:
:
:
:
:
:
:

no
other: Modified DEV L9 (cell multiplication inhibition test)
1975
noother TS: m-cresol, no purity reported

other aquatic plant: Potamogeton lucens
other: photosynthesis
21 day(s)
mg/l
.22
.65
.65
> 1.08

UNEP PUBLICATIONS

101

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:

MethodTest condition
Reliability

:
:
:

no
1983
no
other TS: m-cresol, no purity reported
simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 uS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions not indicated. No
information about application mode, number of plants, controls, test
concentrations, statistics, analytics.

07.05.2004(76)

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton coloratus
other: photosynthesis
21 day(s)mg/l
1.08> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 uS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions not indicated. No
information about application mode, number of plants, controls, test
concentrations, statistics, analytics.

no
1983
no
other TS: m-cresol, no purity reported

07.05.2004(76)

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton crispus
other: photosynthesis
21 day(s)mg/l
1.08> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 uS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions not indicated. No
information about application mode, number of plants, controls, test
concentrations, statistics, analytics.

no
1983
no
other TS: m-cresol, no purity reported

07.05.2004
Species
Endpoint
Exposure period

102

(76)
:
:
:

Agmenellum quadruplicatum (Algae)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Unit
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result:Reliability

:

1974
no
other TS: m-cresol, no purity reported
algae cells embedded in agar, test substance absorbed ondiscs (12.7 mm) which are placed directly on the agar
surfaceincubation 5 to 8 days
no effect with 0.5 mg test substance on the platewith 1 mg inhibition between 1 to 10 mm from the disc edge,
with 10 mg complete killing within a zone of 36 mm(3) invalid
Unsuitable test system

10.05.2004(77)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

other algae: Chlorella autotrophica

Method:Result:Reliability:

algae cells embedded in agar, test substance absorbed ondiscs (12.7 mm) which are placed directly on the agar
surfaceincubation 5 to 8 days
with 1 mg inhibition between 1 to 4 mm from the disc edge,
with 2 mg 1nhibition between 3 to 35 mm from the disc edge
(3) invalid
Unsuitable test system

1974
noother TS: m-cresol, no purity reported

10.05.2004(77)

Species
Endpoint
Exposure period
Unit
TT
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Scenedesmus quadricauda (Algae)
biomass
96 hour(s)mg/l40RemarkReliability::

TT = toxicity treshold(3) invalid
Methodological deficiencies

noother: Cell multiplication inhibition test
1959
noother TS: m-cresol, no purity reported

07.05.2004
Species
Endpoint
Exposure period
Unit
MTL
Method
Year

(70)
:
:
:
:
:
:
:

Ankistrodesmus falcatus (Algae)
biomass
10 day(s)
mg/l
100
1976

UNEP PUBLICATIONS

103

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

GLP
Test substance::noother TS: m-cresol, no purity reported

Method:RemarkResult::Reliability:

described in: Denson & Bold, The University of Texas
Publication No. 6022, 72 (1960)
MTL = median tolerance limit
sublethal concentration 100 mg/l
lethal concentration 500 mg/l(4) not assignable
Insufficient documentation

12.05.2004
4.4

(78)

TOXICITY TO MICROORGANISMS E.G. BACTERIA

TypeSpecies
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
activated sludge, domestic
3 hour(s)
mg/l
461.4
no
OECD Guide-line 209 "Activated Sludge, Respiration Inhibition Test"
1985
noother TS: m-cresol, reagent grade

Remark:Test condition
Reliability

:
:

Flag
07.05.2004:

synthetic sewage stock solution slightly different from OECD
guideline; reference substance 1,5-dichlorophenol
21 degrees C; continuous aeration with 0.5-10 l/min(1) valid without restriction
Guideline study
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
EC75
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
activated sludge of a predominantly domestic sewage

Method:RemarkTest condition
Reliability

:
:
:

Flag
07.05.2004:

Quantitative determination of the nitrification rate (1ststep, NH4 to NO2),
colorimetric measurement of the NO2/NO3 concentration;
static test system
Pre-cleaned activated sludge in particle-free communal waste
water (BOD5: 250 mg/l; NH4-N/l: 50-80 mg)
effect: inhibition of ammonia oxidation
Exposure period: 2-4 h; 25 degree C; pH 7.6-7.8(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

104

(79)

mg/l
11.4
no
other: inhibition of nitrification process
1966
noother TS: m-cresol, no purity reported(80)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Type
Species
Exposure period
Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
other bacteria

Method:Result:

Test condition
Reliability::

6 different pure bacteria cultures: 3 isolated from alaboratory activated sludge, 2 from activated sludge from amunicipal plant receiving some industry wastewater, and 1
from a lake sediment
Effect: 50 % resazurin reduction (determination of
dehydrogenase activity)from laboratory sludges: EC50 = >500, 225, and 410 mg/l
from activated sludges: EC50 = 360 and >500 mg/l
from lake sediment: EC50 = >500 mg/l
21 degrees C; incubation 30-60 min(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail

no
other
1985
no
other TS: m-cresol, purity 99.5 %12.05.2004

(81)

Type
Species
Exposure period
Unit
IC 50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Aerobic heterotrophic
49 hour(s)
mg/l
440
no

MethodRemark::Test condition
Reliability::

culture obtained from mixed liquor of a treatment plant
Effect: inhibition of respiration; prolonged incubationcompared with ISO 8192
25 and 35 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

1991
noother TS: m-cresol, no purity reported

07.05.2004

(82)

Type
Species
Exposure period
Unit
IC 50
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::aquatic
other bacteria: Methanogenic bacteria
96 hour(s)
mg/l
890
no
other: Owen, W.F.: Bioassay for Monitoring Biochemical Methane Potential
and Anaerobic Toxicity. Water Res. 13, 485 (1979)1991
noother TS: m-cresol, no purity reported

UNEP PUBLICATIONS

105

OECD SIDS
4. ECOTOXICITY
RemarkTest condition
Reliability

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:::

Effect: inhibition of gas production
35 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

07.05.2004

(82)

Type
Species
Exposure period
Unit
IC 50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Nitrosomonas sp. (Bacteria)
24 hour(s)
mg/l
.78
no
other: Inhibition of nitrification, comparable to ISO/DIS 9509
1991
noother TS: m-cresol, no purity reported

MethodRemarkTest condition
Reliability

:
:
:
:

culture obtained from mixed liquor of a treatment plant
Effect: inhibition of N-oxidation
25 degrees C(3) invalid
In principal the test is comparable to standard methods,
but the authors state that the compounds with log IC50<1,5 umol/l had
questionable accurate results, so that this effect value has to be consideredinvalid.
(82)

Type
Species
Exposure period
Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
anaerobic microorganisms

Method:Result:Reliability:

phenol-enriched methanogenic culture
nominal concentrations 50, 100, 150, 250, 300, 400, 500, and
700 mg/l m-cresol + 200 mg/l phenol
incubation at 35 degrees C
m-cresol concentrations above 150 mg/l inhibited theanaerobic phenol degradation(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

07.05.2004

yes
1989
no
other TS: m-cresol, no purity reported

07.05.2004
Type
Species
Exposure period
Unit
TT
Analytical monitoring
Method
Year
GLP

106

(46)
:
:
:
:
:
:
:
:
:

aquatic
Pseudomonas putida (Bacteria)
16 hour(s)
mg/l
53
no
other: Cell multiplication inhibition test
1977
no

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Test substance:other TS: m-cresol, no purity reported

Remark:Reliability:

TT = Toxicity threshold; determined at 3 % effect compared
to control(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

07.05.2004(75) (72)Type
Species
Exposure period
Unit
EC10
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Mixed marine bacteria culture
16 hour(s)
mg/l
33.4
324 - 326
noother: Static bioassay (determination of bacterial growth)
1989noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

mixed culture of 13 unidentified bacterial strains isolated
from sea water
Incubation at 25-30 degrees Celsius, artificial saltwater(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004(83) (84)Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Chilomonas paramaecium (Protozoa)
48 hour(s)
mg/l
114
no
other: cell multiplication inhibition test1980
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

TT = Toxicity threshold; determined at 5 % effect compared
to control
20 degrees C; initial pH 6.9(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004
Type
Species
Exposure period
Unit
TT
Analytical monitoring
Method
Year
GLP

(85)
:
:
:
:
:
:
:
:
:

aquatic
Entosiphon sulcatum (Protozoa)
72 hour(s)
mg/l
31
no
other: cell multiplication inhibition test
1978
no

UNEP PUBLICATIONS

107

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Test substance:other TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

TT = Toxicity threshold; determined at 5 % effect compared
to control
25 degrees C; initial pH 6.9(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

(86)

Type
Species
Exposure period
Unit
LC100
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Tetrahymena pyriformis (Protozoa)
24 hour(s)
mg/l
375
no
other: Microtox
1978
noother TS: m-cresol, no purity reported

Test condition
Reliability::

28 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(87)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Uronema parduzci (Protozoa)
20 hour(s)
mg/l
62
no
other: cell multiplication inhibition test1980
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

TT = Toxicity threshold; determined at 5 % effect compared
to control
25 degrees C; initial pH 6.9(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004
Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

108

(88)
:
:
:
:
:
:
:
:
:
:

aquatic
Photobacterium phosphoreum (Bacteria)
5 minute(s)
mg/l
11
no
other: Microtox assay
1983
no dataother TS: m-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Remark:Reliability:

07.05.2004

effect: reduction of bioluminescence
Secondary literature. Not enough information supplied for assessment.
Although the author suggests that Microtox may lack reproductibility due tovariations in bacterial cell suspensions, no information is supplied on themaintenance of the lyophilized bacteria, their age, duration of reconstitution
and other important parameters.
(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.
(89)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Photobacterium phosphoreum (Bacteria)
15 minute(s)
mg/l
8
no
other: Microtox assay
1987
noother TS: m-cresol, analytical grade (either from Merck or EGA Chemie)

Remark:Reliability:

Not enough information supplied for assessment of the test used (Testdone according to Beckman manual). Although it is suggested that
Microtox may lack reproducibility due to variations in bacterial cellsuspensions [Bitton G (1983) Bacterial and Biochemical Tests forAssessing Chemical Toxicity in the Aquatic Environment: A Review. Crit
Rev Environ Control 13: 51 -67], no information is supplied on themaintenance of the lyophilized bacteria, their age, duration of reconstitution
and other important parameters.
(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.
(90)

07.05.2004
Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Photobacterium (Vibrio) fischeri (marine)
5 minute(s)
mg/l
8.2
no
other: Microtox assay
1981
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

Although it is suggested that Microtox may lack reproducibility due tovariations in bacterial cell suspensions [Bitton G (1983) Bacterial andBiochemical Tests for Assessing Chemical Toxicity in the Aquatic
Environment: A Review. Crit Rev Environ Control 13: 51 -67], no
information is supplied on the maintenance of the lyophilized bacteria, theirage, duration of reconstitution and other important parameters. In contrast
to Bulich [Bulich AA (1977), Aquatic Toxicology: Second conference ASTM
STP 667, American Society for Testing of Materials, Philadelphia, pp 98 106], pH not buffered.
15 degrees C(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.
(91)

07.05.2004

UNEP PUBLICATIONS

109OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Type
Species
Exposure period
Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
Escherichia coli (Bacteria)
19 day(s)MethodResult::

Test condition
Reliability::

Incubation in microcosms containing sterile sea water
Number of viable cells remained constant
Number of culturable cells decreased, no plasmids weredetected. Changes in membrane protein composition observed.
After transfer into rich medium without test substance,
growth resumed and plasmids were again detectable.
Test concentration 1 µg/l, 18 degrees C(3) invalid
Tested organism not relevant for environment

no
1983
no
other TS: m-cresol, no purity reported

07.05.2004(92) (93)Type
Species
Exposure period
Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
Pseudomonas putida (Bacteria)
48 hour(s)MethodResult
Test condition
Reliability

:
:
:
:

in the culture medium absorbance at 660 nm was measured
absorbance 0.46 with 0.5 g/l and 0.22 with 1 g/l
30 degrees C(3) invalid
Experimental details missing

no
1989
no
other TS: m-cresol, no purity reported

07.05.2004

(94)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Photobacterium phosphoreum (Bacteria)
30 minute(s)
mg/l
11.8
no
other: Microtox
1981
no dataother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

Inhibition of bioluminescence
Secondary literature; not enough information for assessment of cited result
20 degrees C(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals(95)

12.05.2004
Type

110

:

aquatic

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Species:

Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Remark:Test condition:

Reliability:

07.05.2004

other bacteria: gentechnologically constructed luminescent bacteria
originating from wastewater treatment plant
30 minute(s)mg/l
68 measured/nominalnoother: Microtox assay
1986
no dataother TS: m-cresol, no purity reported
Inhibition of bioluminescence
Modified microorganisms used which represent the metabolic potentials
present in a wastewater treatment plant and some properties of a marineorganism, but which are not identical to any known species in naturalenvironments- Wastewater bacteria (Eschericia coli) which were obtained from awastewater treatment plant- Bacteria obtained the luciferase operon of Vibrio fischeri by transfer fromluminescent E. coli
- Incubation at 20 °C- Result calculated from the difference of the luminescence between
controls and test substance taking into account the light emissions at 0 and
20 °C(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.
(95)

Type
Species
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
Escherichia coli (Bacteria)
2 hour(s)
mg/l
1000

Result:

Test condition
Reliability::

endpoint related to growth inhibition
no effect on cell size
37 degrees C(3) invalid
Methodological deficiencies

1954
noother TS: m-cresol, no purity reported

12.05.2004

(96)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Escherichia coli (Bacteria)

Method:Remark:test organisms isolated from river water
endpoint: inhibition of glucose metabolism
TT = toxicity treshold; determined at 5 % effect compared to

mg/l
600
no
1959
no
other TS: m-cresol, no purity reported

UNEP PUBLICATIONS

111

OECD SIDS
4. ECOTOXICITY

Reliability

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:

control(3) invalid
Methodological deficiencies

07.05.2004(70) (97)Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Pseudomonas fluorescens (Bacteria)

Remark:Reliability:

TT = toxicity treshold; determined at 5 % effect compared tocontrol
endpoint: inhibition of glucose metabolism(3) invalid
Methodological deficiencies

mg/l
40
no
1960
no
other TS: m-cresol, no purity reported

07.05.2004

(70)

Type
Species
Exposure period
Unit
EC0
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Pseudomonas Stamm Berlin 33/2

RemarkReliability::

Effect endpoint: cell multiplication inhibition(4) not assignable
Insufficient documentation

mg/l
180
no
other
1982
no
other TS: m-cresol, no purity reported

07.05.2004

(58)

Type
Species
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

aquatic
Paramaecium caudatum (Protozoa)

ResultReliability::

pertubation level 0.9 mg/l(4) not assignablesecondary literatureother TS: m-cresol, no purity reported

12.05.2004
Type
Species
Exposure period
Unit
Method
Year
GLP

112

(71)
:
:
:
:
:
:
:

aquatic
other protozoa: Vorticella campanula

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Test substance:other TS: m-cresol, no purity reported

ResultReliability::

pertubation level 0.5 mg/l(4) not assignablesecondary literature

12.05.2004

(71)

4.5.1

CHRONIC TOXICITY TO FISH

4.5.2

CHRONIC TOXICITY TO AQUATIC INVERTEBRATES

4.6.1

TOXICITY TO SEDIMENT DWELLING ORGANISMS

4.6.2

TOXICITY TO TERRESTRIAL PLANTS

Species
Endpoint
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other terrestrial plant: Lactuca sativa Ravel R2
growth14 day(s)mg/kg soil dw
96
OECD Guide-line 208 "Terrestrial Plants, Growth Test"
1993
no dataother TS: m-cresol, purity >= 95 %MethodResult::Reliability:

Flag
07.05.2004:

analytical monitoring at start and end of test
EC50 based on nominal concentration; for most of theexamined phenols (including m-cresol) applied concentrations dropped but
remained larger than 50 % of the nominal values.
The 7-d EC50 was 69 mg/kg soil (original dimension µg/g soil).
(2) valid with restrictions
Guideline study; applied test concentrations not stable
during the test period
Critical study for SIDS endpoint(98)

Species
Endpoint
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Lactuca sativa (Dicotyledon)
emergence
3 day(s)mg/l53other: Seed germination test
1978
noother TS: m-cresol, no purity reported

Method:Result:As described by Reynolds 1975 (Characterization of osmotic restraints on
lettuce fruit germination. Ann. Bot. 39, 791-796) and 1977 (Comparative
effects of aliphatic com-pounds on inhibition of lettuce fruit germination.
Ann. Bot. 41, 637-648)- Lettuce cultivar Great Lakes- Germination temperature 30 °C
Result was reported as "0.49 mmol/l" which equals 53 mg/l

UNEP PUBLICATIONS

113

OECD SIDS
4. ECOTOXICITY
Reliability

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:(2) valid with restrictions
Basic data given

07.05.2004(99)

Species
Endpoint
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other terrestrial plant: Lactuca sativa Ravel R2
growth16 day(s)mg/l50

Method:Result:Reliability:

semistatic test in nutrient solution, renewed 3 times/week
nutrient solution as described in Steiner, A.A.: Soilless
culture. Proceedings, Sixth Colloqium of the International
Potash Institute, Florence, Italy, 324-341 (1968);
analytical monitoring of TS at start and end of exposure andbefore renewal of test solution
EC50 based on nominal concentration; TS concentration before renewal oftest solution > 50% of initial concentration(3) invalid
unsuitable test system(98)

07.05.2004

1993
no dataother TS: m-cresol, purity >= 95 %Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Raphanus sativus (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilled water
24 degrees C, 10h light, 14 h dark
3 replicates of 20 seeds
Concentr. Germination rate% Growth rate %g/l
1 day 4 days Radicle Hypocotyl

Reliability

:

1989
no
other TS: m-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10
0
0
1
0
5.3
2.0
0.1
82.6 95.0
80.8(3) invalid
Methodological deficiencies

104.7

07.05.2004(100)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Brassica rapa (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:seeds exposed to test compounds dissolved in distilled water

114

1989
no
other TS: m-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

ResultReliability

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004::

24 degrees C, 10h light, 14 h dark
3 replicates of 20 seeds
Concentr. Germination rate% Growth rate %g/l
1 day 4 days Radicle Hypocotyl
10
0
0
1
0
0
0.1
85.8 91.5
54.9(3) invalid
Methodological deficiencies

72.8

07.05.2004(100)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Brassica campestris var. chinensis (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilled water
24 degrees C, 10h light, 14 h dark
3 replicates of 20 seeds
Concentr. Germination rate% Growth rate %g/l
1 day 4 days Radicle Hypocotyl

Reliability

:

1989
no
other TS: m-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10
0
0
1
0
0
0.1
100
100
86.5
(3) invalid
Methodological deficiencies

77.1

07.05.2004

(100)

4.6.3

TOXICITY TO SOIL DWELLING ORGANISMS

4.6.4

TOX. TO OTHER NON MAMM. TERR. SPECIESSpecies
Endpoint
Exposure period
Unit
LD50 oral
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other avian: Agelaius phoeniceus (red-winged blackbird)
mortality

Test condition:

Reliability:

birds pre-conditioned to captivity for 2 to 6 weeks
dosed by gavage with solution in propylene glycol or bypellets resp. gelatin capsules(2) valid with restrictions
Unsuitable test system

mg/kg bw
113
1983
no dataother TS: m-cresol, no purity reported

07.05.2004(101)

UNEP PUBLICATIONS

115

OECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

4.7

BIOLOGICAL EFFECTS MONITORING

4.8

BIOTRANSFORMATION AND KINETICS

Remark:Test substance
Reliability::

In aquarium water of 12 species of freshwater fish 48 h
after exposure to 3-15 mg/l m-cresol, cresyl sulphate(55-64% of 14C recovered) or m-hydroxybenzoic acid (0-39 %)were foundIn bile of 11 species, cresyl glucuronide (63-74 %), cresyl
sulphate (8-20 %) and m-hydrobenzoic acid (5-12 %) were
foundUnchanged m-cresol detected in both aquarium water and bile
m-[U-14C]cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail17.10.2001
4.9

(102)

ADDITIONAL REMARKS

Memo

:

Sea urchin test

Remark:Test substance:

Reliability:

Strongylocentrotus droebachiensis (sea urchin):static test, 5 degrees C
Determined effect endpoints: death, pathology, inhibition ofcleavage and differentiation, pigment defects
EC50 (96 h): ca. 30 mg/lother TS: m-cresol, purity > 98 % as determined by GC (obtained from
Merck)(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

(57)

Memo

:

Tree neoplasms

Remark:Test substance
Reliability::

m-cresol (1.5 % v/v) showed a toxicity rating from 3-4 (0 =no injury, 5 = complete kill within 14 d) in tomato crowngall tumors incited by Agrobacterium tumefaciens.
other TS: m-cresol, no purity reported(3) invalid
Unsuitable test system

07.05.2004

(103)

Memo

:

Hela cell screening

Remark:Test substance
Reliability::

In a rapid-cell culture assay with HeLa cells, m-cresol(4x10-5 to 4x10-3 M, 4 h incubation) showed aconcentration-dependent inhibition of 3H labeled thymidine
incorporation into DNA
incubation 4 hother TS: m-cresol, no purity reported(3) invalid

116

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
Unsuitable test system

07.05.2004(104) (105)

Memo

:

MolluscRemark:Test substance
Reliability::

Teredo diegensis (Mollusca):
LC50 (72 h): 100 mg/lother TS: m-cresol(4) not assignable
Reference not available

07.05.2004(64)

UNEP PUBLICATIONS

117

OECD SIDS
5. TOXICITY
5.0

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

TOXICOKINETICS, METABOLISM AND DISTRIBUTIONIn Vitro/in vivo
: In vivo
Type: Distribution
Species: dog
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle:Route of administration
Exposure time
Product type guidance
Decision on results on acute tox. tests
Adverse effects on prolonged exposure
Half-lives: 1st:
2nd:rd
3 :Toxic behaviour:
Deg. product:Result:Reliability:

25.10.2002

:
:
:
:
:

oral unspecified

Following oral exposure cresols in the body initially concentrate in the
blood, liver, brain followed by more widespread distribution in the lungs,
kidneys and other unspecified organs (no further details given)(4) not assignablesecondary literature(106)

In Vitro/in vivo
: In vivoType: Toxicokinetics
Species: rabbit
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle: other: sodiumhydroxycarbonate
Route of administration: gavage
Exposure time:
Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:
Toxic behaviour:
Deg. product:
Method: other: see freetext ME
Year: 1949GLP: no
Test substance: other TS: m-cresol, not specified further
Method118:

Approx. 200 mg/kg bw was administered to 10 rabbits (sex not mentioned)
as single dose as solution in bicarbonate by gavage. Urine was collected
over a period of 24-48 hours and the levels of free and conjugated cresol
was estimated by the method of Folin O. and Ciocalteu V., J. biol. Chem.
73, 627 (1927). Metabolites were identified with the method described in

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Result:Reliability:

Flag
06.02.2004:

Bray et al., Biochem J. 41, 212 (1947) and 43, 561 (1948)
absorption and excretion:
Within 24 hours 84 % of the m-Cresol dose was excreted in the urine
indicating that at least this amount was absorbed through thegastrointestinal tract and urinary excretion was the main route ofelimination.
metabolism:
The principal metabolic pathway was conjugation wit h glucuronic andsulphuric acids: 10% of the dose were discovered as ethereal sulphate and60% of the dose as etheral glucuronide and 1% of the dose as free cresol.
About 3 % of the dose was conjugated 2,5-dihydroxytoluene; conjugated
3,4-dihydroxytoluene was only discovered in traces.
(2) valid with restrictions
no information on sex of rabbits used, no information on distribution in thetissueCritical study for SIDS endpoint(107) (108)

In Vitro/in vivo
: In vitroType: Absorption
Species: other: human skin
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle: water
Route of administration: dermal
Exposure time
: 250 minute(s)Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:
Toxic behaviour:
Deg. product:
Method
:
Year
:
GLP
:
Test substance: other TS: m-cresol, not specified further
Method:Result:Reliability:

Flag
06.02.2004:

In Vitro/in vivo
Type
SpeciesNumber of animals:::

The permeability of m-Cresol was measured across 2.5 cm2 epidermal
membranes from human abdominal skin. The membranes were supported
in a glass cell and the amount of m-Cresol passing to the receptor vessel
measured spectrophotometrically. Each test was conducted at least in
duplicate and at 25 Degree Celsius
The permeability coefficient of m-Cresol was 2.54 x10 (exp)-4 cm/min andthe lag time for a 0.4%w/v solution was 15 min. The thresholdconcentration for damage i.e. the aqueous concentration at which thepermeability coefficient began to increase was 1.0 %w/v.
(2) valid with restrictions
in vitro investigation
Critical study for SIDS endpoint(109)
In vivoother: dogs and rabbits

UNEP PUBLICATIONS

119OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
Males
Females::

Males
Females

:
:
:

Doses
VehicleRoute of administration: oral unspecified
Exposure time:
Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:
Toxic behaviour:
Deg. product:
Method
:
Year
:
GLP
:
Test substance: other TS: m-cresol, not specified further
Remark:Reliability
Flag
06.02.2004::

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males
Females
VehicleMethodYear
GLP
Test substance:::

Result:Reliability:

Flag
06.02.2004:

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females

:
:
:

120

m-Cresol undergoes entero-hepatic circulation when administered orally todogs and rabbits.
(2) valid with restrictions
Critical study for SIDS endpoint(110) (111)
In vivo
Toxicokinetics
other

:
:
:
:
:
:
:
:
:

other TS: m-cresol, not specified further
At physiological pH, the conjugated metabolites of phenolic compounds are
ionized to a greater extent than the parent compound, which reduces renal
reabsorption and increases elimination with the urine.
In addition to urinary excretion, cresols are excreted in the bile, but themost part undergoes enterohepatic circulation. There are known species
differences in the specific conjugation reactions of cresol isomers and therelative amounts of glucuronide and sulfate conjugates therefore differ
between species and also vary with dose.
(2) valid with restrictions
basic information
Critical study for SIDS endpoint(110) (112) (113) (114)
In vivo
Absorption
rat

:
:

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Doses
Males
Females:::

10 mg/m3, 4 hrs a day for 100 d up to 4 months
VehicleRoute of administration: inhalation
Exposure time
: 4 hour(s)Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:
Toxic behaviour:
Deg. product:
Method
:
Year
:
GLP
:
Test substance: other TS: m-cresol, not specified further
Result:Reliability:

Flag
06.02.2004

:

5.1.1

Female rats were exposed to 10 mg/m3 m-cresol 4 hours perday, daily for 100 d up to 4 months. m-Cresol reached aconcentration of 12.2 ug/g lung tissue; the neutral red
sorption on day 3 resp d 39 was 133 % resp. 152 % of thecontrol value as a marker for cytotoxicity. Full recovery
did not occur.
(2) valid with restrictions
information on absorption via lung, but study description suffer fromdeficiencies
Critical study for SIDS endpoint(115)

ACUTE ORAL TOXICITY

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:LD50
242 mg/kg bw
rat
male
5
other: noneother: 5 rats/dose group, 4 doses, undiluted liquid, time of recovery: up to
14 days1969
no dataother TS: m-cresol, purity not given, M.P.: 11-12 C, B.P.: 202,8 C
dosage onset of sympt.
mortality
mortality
mg/kg bw
0-4 hrs
0-4hrs day3 day6 day7 cumulat.
147
215
316
464

S
S
S
S

1/5
3/5
4/5

1/5
1/5

1/5

0/5
2/5
4/5
5/5

S=signs of intoxication: Hypoactivity, tremors, convulsions,salivation, prostration
survivors: recovery within observation time, gross necropsy:
no significant findings

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121

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
decedents, gross necropsy: inflammation of thegastrointestinal tract, hyperemia of lungs, liver andkidneys(2) valid with restrictions
no information on strain used , no information on statistical evaluation given
Critical study for SIDS endpoint(116) (117)

Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 2010 mg/kg bw
rat
no datano data

Reliability:(4) not assignablesecondary citation

LD50= 2020 mg/kg bw
rat
Wistarmale/female
10
other: olive oil
1500, 1700, 2000, 2200, 2400 mg/kg bw
other: 5 rats/sex/dose, 6 doses, administration as a 10% solution in olive oil
to non-fasted Wistar rats by gavage to give doses of 1500-2700 mg/kg bw,
observation time was not reported, section was not performed
1944
no dataother TS:m-cresol, purity: 96-98 %1500 mg/kg: 0 % dead, 1700 mg/kg: 20 % dead, 2000 mg/kg: 40 % dead,
2200 mg/kg: 70 % dead, 2400 mg/kg: 70 % dead,time of death not mentioned
signs of poisoning: twitching of isolated bundles of muscles anduncoordinated movement of the legs, irregular pulse and difficulties inbreathing(2) valid with restrictions
post-exposure observation time not reported
Critical study for SIDS endpoint(118)

other: oilno dataother: 10 % solution was used1974
no dataother TS: m-cresol, not specified further

06.02.2004
Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method122(112) (119)
:
:
:
:
:
:
:
:
:

LD50
= 520 mg/kg bw
rat
male
10
water
other: 10 rats/ dose were fed with a 10 % aqueous solution, 5 doses,
observation period: 14 d, gross examination

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Year
GLP
Test substance

:
:
:

1949
no
other TS: purity no data

Remark:Reliability:

at the dosage level used the rats developed tremor within a
few minutes, deaths occurred within a few hours(4) not assignable
Documentation insufficient for assessment

18.09.2002

(120)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 828 mg/kg bw
mouse

Reliability:(4) not assignablesecondary citation

no dataother: oilother: 10 % oil solution
1974
no dataother TS: purity not mentioned

17.12.2002(112) (119)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Result:Reliability:

10.01.2003
Type:other: dose selection study for MNT
mouse
male/female
6other: corn oil
400, 800, 1200, 1600, 2000 mg/kg bw (dose volumes: 5 ml/kg bw)
other: 3 mice/sex and dose received one dose by gavage:
400,800,1200,1600,2000 mg/kg bw, post dose observation for 2 d for toxic
effects and mortality
1989
yesother TS: Purity: 99.8 %the study was performed in order to select doses for a mouse in vivo bonemarrow cytogenetic assay (see chapter 5.6)
2000 mg/kg:immediately after dosing all mice showed
convulsions, experienced difficulties in breathing, and were
extremely lethargic; mortality: 6/6
1600, 1200 mg/kg: all mice showed convulsions 2-4 min. after
dosing, experienced breathing difficulties and lethargy;
mortality: 1600 mg/kg: 6/6; 1200 mg/kg: male 1/3, female
2/3, all other rats showed signs of recovery
800 mg/kg: all mice showed convulsions 4-5 min. after dosingwith difficulty in breathing and lethargy, no rat died; allshowed signs of recovery after 2 d
400 mg/kg: all mice apparently healthy(2) valid with restrictions
only 2 days post-exposure observation;
preliminary dose range finding study(121)
other: LD

UNEP PUBLICATIONS

123

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:= 1400 mg/kg bw
rabbitno data1other: waterother: single oral gavage of a 20 % aqueous emulsion, 4 doses, time till
death was recorded
1944
no dataother TS: purity not mentioned
620 and 940 mg/kg: no death; 1400 mg/kg: 8 hrs until death;
2100 mg/kg 90 min. till death(4) not assignable
study reporting suffers from deficiencies

17.12.2002

(118)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

other: LD
640 - 1000 mg/kg bw
dog

Remark:Reliability:

640 mg/kg: transitional aggitation, staggering gait,
sedation, recovery
1000 mg/kg: death within 30 min after application probably
due to aspiration(4) not assignable
study reporting suffers from deficiencies

no data2
no dataother: single application by gavage, no further data
1907
no dataother TS: no data on purity

17.12.2002
5.1.2

(111)

ACUTE INHALATION TOXICITY

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Exposure time
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability

:

124

LC50
> .71 mg/l
rat
male
6
other: air
1 hour(s)other: 6 rats exposed to 0.71 mg/l for 1 hr, room temperature, up to 14 dpost exposure observation, gross necropsy
1969
no dataother TS: m-cresol, M.p.: 11-12 C; B.P.: 202.8 C
Mortality. 0/6; signs of intoxication: none; gross autopsy:
no significant findings(2) valid with restrictions

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:Result:Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Exposure time
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability:

no information about strain used, exposure time : 1 hr, only one
concentration
Critical study for SIDS endpoint
(116)
LC50
= 58 mg/m³
rat
no datano datano datano dataother: aerosol-exposure; no further data1975
other TS: m-cresol, not specified further
the mean lethal concentration of m-cresol was measured. The original data
are not published and no further experimental details are availabel from theciting literature
Clinical signs of toxicity included irritation of mucous membranes,
neuromuscular excitiation and convulosions; hematuria at very highconcentrations (no further information)(2) valid with restrictions
Secondary citation from peer-reviewed data source
Critical study for SIDS endpoint(122)
other: inhalation of mistrat
no data
6
8 hour(s)other: mist was generated by holding the compound in a bath of 170
degree Celsius, observation period: 14 d1949
noother TS: no data on purity
all rats survived the exposure period; only 1/6 failed togain weight during the observation period(4) not assignable
documentation suffers from significant deficiencies

18.09.2002
Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Exposure time

(120)
:
:
:
:
:
:
:
:
:

other: inhalation of saturated vapour
rat
no data6other: air
8 hour(s)UNEP PUBLICATIONS

125OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Method:Year
GLP
Test substance:::

Remark:Reliability:

Flag
06.02.2004

:

5.1.3

other: exposure to saturated vapour produced at room temperature by
bubbling air at 2.5 l/min, observation period 14 d1949
noother TS: m-cresol, not specified further
m-Cresol did not affect rats in 8 h exposure periods, all of the rats gained
weight during the observation period(2) valid with restrictions
description considered of sufficient quality to allow evaluation
Critical study for SIDS endpoint(120)

ACUTE DERMAL TOXICITY

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 1100 mg/kg bw
rat

Reliability:(4) not assignablesecondary citation

no datano dataother: no data
1974
no dataother TS: no data

17.12.2002(112) (119)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:

LD50= 2050 mg/kg bw
rabbitno datano data5other: none
1000, 1470, 2150, 3160 mg/kg bw
other: 5 rabbits/dose, 4 doses, exposure time not mentioned, up to 14 days
post exposure observation time1969
no dataother TS: m-cresol, M.P.: 11-12 C; B.P.: 202.8 C
Dosage onset of symp.
mortality
mg/kg 4-12 hrs
12-24 hrs day3
1000
1470
2150
3160

S
S

4/5
4/5

mortality
cumulative
0/5
0/5
4/5
4/5

S = signs of intoxication from 4 hrs up to 12 hrs p.a.:lacrimation, salivation,
hypersensitivity, convulsion, hypoactivity:dermalirritation: severely burned, severe edema

126

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
gross necropsy-survivors: no significant findings
gross necropsy-decedents: hyperemia of lungs and kidneys(2) valid with restrictions
no information about strain used, statistical evaluation not given
Critical study for SIDS endpoint

Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 2830 mg/kg bw
rabbit

Method:Reliability:

Flag
06.02.2004:

The method used was essentially that of Smyth et al. 1962 (Am. Ind. Hyg.
Ass. J. 23, 95-107) except three females/dose were tested 24 hr occlusive
exposure to the neat material was followed by a 14-day observation period.
the most probable LD50 value was determined by the method ofThompson 1947 (Bact. Rev.11, 115-145) of moving averages. Clinicalsigns and purity of the Ts are not reported.
(2) valid with restrictions
no guideline study: Doses used, clinical signs and purity of Test substanceare not reported
Critical study for SIDS endpoint
(123)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability

:

(116)

female3no dataother: see freetext ME
1977
no dataother TS: m-cresol, not specified further

LD50= 1860 mg/kg bw
rabbitmale
10other: undiluted
other: application to the slipped trunk of rabbits for 24 hours under 'Vinylite'
sheeting, gross examination1949
noother TS: purity no data
original data: 1.80 ml/kg
severe necrosis and erythema of the skin and kidney damage(bloody urine in the urinary bladder), congested pancreas,mottled liver and abdominal wall hemorrhagia were noted(4) not assignable
documentation insufficient for assessment

18.09.2002
5.1.4

(120)

ACUTE TOXICITY, OTHER ROUTES

Type
Value
Species
Strain

:
:
:
:

LD50
= 168 mg/kg bw
mouse

UNEP PUBLICATIONS

127

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Sex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Reliability:

no datano datai.p.
unspecified
other: no datano(4) not assignableunusual application route18.09.2002

(124)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time

:
:
:
:
:
:
:
:
:
:

other: LD= 100 mg/kg bw
guinea pig

Reliability:(4) not assignableunusual application routeno datai.p.

18.09.2002

(124)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Reliability:

other: LD= 900 mg/kg bw
rat
no dataother: no datas.c.
other: no datanoother TS: no data
(4) not assignableunusual application route18.09.2002
Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
Method
Year

128

(124)
:
:
:
:
:
:
:
:
:
:
:
:

other: LD= 450 mg/kg bw
mouse
no datawaters.c.
othe: no data
1905

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

GLP
Test substance::noother TS: no data

Reliability:(4) not assignableunusual application route18.09.2002

(125)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time

:
:
:
:
:
:
:
:
:
:

other: LD= 500 mg/kg bw
rabbitReliability:(4) not assignablesecondary literatures.c.

18.09.2002

(126)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
Method

:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

other: LDcatno data1other: olive oils.c.
other subcoutaneous admininstration of a 10 % solution, 1 cat/dose 7
doses, hours till death were recorded
1944
no dataother TS: 10 % in olive oil
hours until death:
80 and 120 mg/kg: no death; 180 mg/kg: 27 hours, 280 mg/kg:
4 hours; 420 mg/kg: 12 hours; 620 mg/kg: 7 hours; 940 mg/kg:
5.5 hours(4) not assignableunusual application route18.09.2002

(118)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time

:
:
:
:
:
:
:
:
:
:

other: LD= 120 mg/kg bw
cat

Reliability:(4) not assignableunusual application routes.c.

18.09.2002(125)

UNEP PUBLICATIONS

129

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Reliability:

other: LD
ca. 120 mg/kg bw
cat
no datano datas.c.
other: no data1905
noother TS: no data
(4) not assignableunusual application route18.09.2002

(125)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time

:
:
:
:
:
:
:
:
:
:

other: LD= 300 mg/kg bw
guinea pig

Reliability:(4) not assignableunusual application routeno datas.c.

18.09.2002

(124)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Reliability:

other: LD= 250 mg/kg bw
other: frog
no data
1
water
s.c.
other: no data1905
noother TS: no data
(4) not assignableunusual application route05.02.2004
Type
Value
Species
StrainSex
Number of animals
Vehicle
Doses

130

(125)
:
:
:
:
:
:
:
:

other: LD
rabbit1other: water

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Route of admin.
Exposure time
Method

:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

i.v.
other: intravenous injection to 1 rabbit per dose of an 0.5 % aqueous
solution, 4 doses, time until death was recorded
1944
no dataother TS: purity no data
hours until death: 120 and 180 mg/kg: no death; 280 mg/kg:
15 hours; 420 mg/kg: 7 hours(4) not assignableunusual application route18.09.2002

(118)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Reliability:

other: LD= 150 mg/kg bw
dog
no dataother: no datai.v.
other: no datanoother TS: no data
(4) not assignableunusual application route18.09.2002
5.2.1

(124)

SKIN IRRITATION

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

rabbit.5 other: ml
Semiocclusive
4 hour(s)6Method:Reliability

:

Flag

:

TS applied to the clipped backs or flanks of the rabbits. The material wascovered by a surgical gauze two layers thick, gauze patches were held inplace with strips of Elastoplast tape for 4 hours. After 4 hrs the patches
were carefully removed and the test areas were evaluated for visible tissue
destruction.
evaluation criterias:
When visible tissue destruction occurred in at least 2/6 rabbits, the test
materials were classified as corrosive (no further details given).
(2) valid with restrictions
Limited documentation
Critical study for SIDS endpoint

corrosiveother: see freetext ME
1977
no dataother TS: m-cresol, not specified further

UNEP PUBLICATIONS

131OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

06.02.2004(123)

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability:

Flag
06.02.2004:

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

rabbitundiluted
no datano data6highly irritatingother: 0.5 ml undiluted TS was applied to the intact and to the abradedskin, time of observation: 24 and 72 hours
1969
no dataother TS: m-Cresol, M.P.:11-12 C; B.P.: 202.8 C
intact skin, erythema. edema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6
abraded skin, erythema, edema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6
no tissue destruction and/or necrosis reported, no further details reported
Summary: irritation score: 8.00/8.00(2) valid with restrictions
limited documentation; no information on exposure time and conditions
Critical study for SIDS endpoint(116)
rabbitother: see methodno datano data5highly irritatingother: 0.01 ml on the skin of the rabbit belly: undiluted and 10 % solution in
acetone1949
noother TS: no data on purity
undiluted m-cresol: necrosis of the skin (belly);
10 % solution in acetone: 2/5 severe erythema; 3/5 erythemaand moderate oedema
These reactions relegate to grade 6/10
(4) not assignable
documentation insufficient for assessment

18.09.2002(120)

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
Method

:
:
:
:
:
:
:
:
:
:

Year

:

132

rabbitundiluted
Semiocclusive
4 hour(s)6corrosiveother: conducted in accordance with Fed. Reg.37,No.57§173.240,1972;
evaluated according to Draize, J.Pharm.Exp.Therap. 82, 1944
1974

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

GLP
Test substance::no dataother TS: no data on purity

Reliability:(4) not assignable
documentation insufficient for assessment

18.09.2002(127)

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:Reliability:

rabbitother: see remarks

Paper discs were soaked with 30 ul of m-cresol (dilutions
1:1 to 1:64) and kept secured on the shaved dorsal skin for
30 min. Then 6 ml/kg bw of a 1 % solution of Evan's blue
were injected i.v.. After 10 min the rabbits weresacrificed, the dorsal skin was exfoliated, spread on glass
plates, and lighted from behind. The paper discs were
removed and the sites of application were examined.
The lowest concentration causing dye exsudation was found at
a dilution of 1:16 (6.25 %).
The lowest concentration causing corrosion was found at adilution of 1:2 (50 %).
(4) not assignableunusual test method

18.09.2002
5.2.2

(128)

EYE IRRITATION

Species
Concentration
Dose
Exposure time
Comment
Number of animals
VehicleResultClassification
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

rabbitundiluted.1 ml
unspecified
no data
6

Remark:after 24 hrs: cornea, iris, conjunctivae: 87.3 (mean score) mean score forcornea: 60, mean score for iris: 10, mean score for conjunctivae: 18)
after 48 hrs: cornea, iris, conjunctivae: 87.3 (mean score)mean score for cornea: 60, mean score for iris: 10, mean score for
conjunctivae: 18)
after 72 hrs: cornea, iris, conjunctivae: 87.3 (mean score)mean score for cornea: 60, mean score for iris: 10, mean score for
conjunctivae: 18)

highly irritatingother: undiluted 0.1 ml, time of reading: 24, 48 and 72 hours
1969
no dataother TS: m-cresol, M.P.: 11-12 C; B.P.: 202.8 C

UNEP PUBLICATIONS

133

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability:

Flag
06.02.2004:

Species
Concentration
Dose
Exposure time
Comment
Number of animals
VehicleResultClassification
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

summary: irritation score: 87.3/110(2) valid with restrictions
observation time should be longer to evaluate reversibility
Critical study for SIDS endpoint(116)
rabbitother: see method
unspecified

highly irritatingother: instillation of a 5 % solution and a 1 % solution, solvent: propylene
glycol1949
noother TS: no data on purity
5 % solution: severe damage of the cornea
1.0 % solution: was harmless
result: Grade 9/10
(4) not assignable
documentation insufficient for assessment

18.09.2002

(120)

5.3

SENSITIZATION

5.4

REPEATED DOSE TOXICITY

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Sub-acuteratmale/female
Sprague-Dawley
inhalation
2 weeks (14 exposures)
6 hrs/d, 7 d
2 weekstarget conc.: 20 ug/l of an 0.25 % solution in 1.6 % aquous glycerolother: yes, waterother: see freetext ME
2001
yesother TS: m-cresol, not specified further

Method:6 rats/sex /group, nose-only exposure to an aerosol, target conc. 20 ug/l,target pulmonary dose: 504 ug/kg bw/day
observations for mortality, moribundity twice daily during exposure andduring recovery, clinical observations (hematology, blood chemistry) within
one hour of exposure during exposure and during recovery period, recordof body weight prior to first exposure and weekly during exposure andduring recovery period,
complete necropsy was performed on all animals at completion of
exposure and recovery period including external and internal examination:body orifices, body cavities, external and cut surfaces, record of organ

134

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m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Result:Reliability:

06.02.2004
Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
Method

:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability:

weights at terminal and recovery necropsies: liver, kidneys, lungs, spleen,
adrenal glands, thymus, testes, ovaries, organ weight to terminal bodyweight ratios were calculated.
Microscopic examination on respiratory tract (target tissue) of the first 5
rats/sex/group
statistical methods:
one way analyses of variance (ANOVA)
observed concentration: 27 ug/l, achieved pulmonary dose level: 690 ug/kg
bw
no animal died during the study,
no treatment related clinical signs; incidental observations in all treatmentgroups including control groupswere salivation, diarrhea, wet inguinal fur,
red material around nose and eyes, alopecia, lesions and red material
around nose seen sporadically and in low frequencies during recovery
period.
Body weights, body weight gain, hematology, blood chemistry were notstatistically different from control group.
terminal and recovery sacrifices:no statistically differences in organ weights when compared to controls andno test-article related gross or histopathologic lesions. Observed minor
inflammatory or degenerative changes observed in peribronchial,
perivascular and subserosal regions were evaluated as incidental findings
in rodent inhalation studies(4) not assignable
study suffers from deficiencies: only 1 dose used, solvent (aquous glycerol)
was not the control, detailed data of the results were not presented, result
description did not differ between phenol and m-cresol(129) (129)Sub-acuterat
maleno dataoral feed
28 d
daily
no
0, 20, 150, 500 mg/kg diet (approx. 0, 1.86, 13.95 or 45.8 mg/kg bw/d)yes, concurrent no treatment
ca. 45.8 mg/kg bw
other: 10 rats/group, TS was prepared as a 2.0 % corn oil solution andblended with the diet; diets were prepared fresh weekly. Control rats
received basal diets containing 2 % corn oil, necropsy of all animals
1969
no dataother TS: M.P.:11-12 C; B.P.: 202.8 C
No deaths occurred during the study and no untoward
behavioural reactions were noted.
At necropsy, no significant gross lesions were noted among
the test animals, when compared to the control animals.
(4) not assignable
documentation insufficient for assessment

18.09.2002
Type
Species
Sex
StrainRoute of admin.
Exposure period

(116)
:
:
:
:
:
:

Sub-acuteratmale/female
other: F344/N
oral feed
28 days

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OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

continuously in dietno0, 300, 1000, 3000, 10000 or 30000 ppm (see freetext RM)
yes
3000 ppm
other: see freetext ME1991
yesother TS: purity > 98 %Method:Remark:Result:

SIZE OF STUDY GROUP:
5 male and 5 female mice per group
TIME HELD BEFORE STUDY: 13-15 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into groups per sex
DIET: NIH-07 rat ration
ANIMAL ROOM ENVIRONMENT:
temperature: 72° +/-3° F, humidity: 50 % +/-15 %, Fluorescent light: 12
hrs/day, room air changes : 10-12 changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly, and at termination,
feed consumption by cage recorded twice weekly
NECROPSY AND HISTOLOGIC EXAMINATION:
necropsy and tissue collection performed for all animals. A complete
histopathologic examination was conducted on all control animals, allanimals in the highest dose group with at least 60 % survivors at study
termination, and all aninmals in higher dose groups inclusive of early
deaths. The following organs and/or tissues were included in complete
histopathological examinations, as well as any tissue masses, grosslesions, and associated regional lymph nodes: adrenals, aorta, bone(sternebrae, femur, or vertebrae, including marrow), brain, bronchi, clitoral
gland, epididymis, oesophagus, heart, kidney, large intestines (caecum,colon, rectum), liver, lungs, lymph nodes (mesenteric), mammary glands,
nasal cavity and turbinates, oral cavity, ovaries, pancreas, parathyroids,
pharynx, pituirary, preputial gland, prostate, salivary glands, scrotal sac,seminal vesicles, skin, small intestine (duodenum, ileum, jejunum), spleen,
stomach, testes, thymus, thyroid, tongue, trachea, tunica vaginalis, urinary
bladder, uterus and Zymbal's glands. Target organs and gross lesions
were examined at lower doses until a no-observed chemical effect wasdetermined. Target organs included the following: uterus and ovaries.
Organ weights recorded for brain, liver, right kidney, thymus, heart, andlungs of all animals, and the right testis of all males.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test
mean compound consumption (mg/kg bw/day):males
females0 ppm
00300 ppm
25
251000 ppm
85
82
3000 ppm
252
252
10000 ppm
870
862
30000 ppm
2470
2310
no mortallity; no clinical signs of toxicity were observed
and30000 ppm: mean final body weight sign. decreased: male (p</=0.05),
female (p</=0.01), sign. reduced mean body weight gains, males, femalesp</=0.01); reduced foodconsumption in males and females during the first week ofthe study;
no gross lesions were noted at necropsy,

136

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5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability
Flag
30.04.2003

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
Method

:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Method:at study termination organ weights (w) were sign. increased:
liver: male, abs. w. at 10000 ppm (p</=0.01), rel. w. from 10000 ppm(p</=0.01), females, rel. w. from 10000 ppm (p</=0.05), right kidney: male,
female, rel. w. at 30000 ppm (p</=0.05); brain, male, rel. w. at 30000 ppm,
female, abs. w at 30000 ppm (p</=0.05),rel.w. at 30000 ppm (p</=0.01),
No histomorphologic changes were reported from these organs.
Histological evaluation , characterized by average severity score based ona scale of 1 to 4 (1=minimal, 2=mild, 3=moderate, 4= marked) revealed
effects: uterine atrophy in 4/5 females at 30000 ppm
NOAEL = 3000 ppm (male, female)(1) valid without restriction
Critical study for SIDS endpoint(130)
Sub-chronicratmale/female
Sprague-Dawley
gavage13 w
once daily
1w
0, 50, 150 or 450 mg/kg bw/d in corn oil
yes, concurrent vehicle= 50 mg/kg bw
other: 30 rats/sex/dose, add.10 rats/sex for baseline clin. Pathol., interim
kill at week 7, terminal kill at week 14, blood samples for hematology,
clin.chemistry; urinalysis; gross and microsc. pathology; stat. anal.:
Dunnett's t-t1986
yesother TS: purity: 98.6 %Dose selection was based on the results of a range-finding study
30 rats/sex/dose,
additional 10 rats/sex/dose for baseline clinical pathology
interim kill at week 7.
Body weights were recorded on test day1 and weekly thereafter; individual
food consumption data were collected weekly;
moribund/mortality check twice daily (moribund rats were killed andnecropsied); physical examination weekly; ophthalmologic examination
during quarantine period and in test week 13
HAEMATOLOGY
haemoglobin, haematocrit, protrombin time (PT), erythrocyte count,reticulocyte count, toal and differential leucocyte count, activated partial
thromboplastin time (APTT)
CLINICAL CHEMISTRY
sodium, chloride, potassium, direct and total bilirubin, alkaline
phosphatase, total cholesterol, albumin, CO2, SGPT, SGOT, glucose,
BUN, globulin (calculated), total protein, creatinine, A/G ratio (calculated)
URINALYSIS
appearance, volume, colour, specific gravity, pH, protein, glucose, ketone,
bilirubin, urobilinogen, haemoglobin, microscopic examination
PATHOLOGY
determination of weights of:heart, liver, spleen, brain, kidneys (individually), gonads (individually,
adrenals, thyroid/parathyroid
examination of all control rats and high dose rats at study termination as
well as those that died during the study:
all gross lesions,brain (3 levels), spleen, bone (with marrow), skeletal muscles, salivary

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OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
gland, mammary gland, thymus, thyroid (with parathyroid), lungs (withmainstem bronchi), trachea, liver, urinary bladder, testes, prostate, ovaries,
corpus and cervix uteri, eye, pituitary gland, lymph node, spinal cord, heart,
aorta, siatic nerve, pancreas, oesophagus, kidneys, small and large
intestine, adrenals, stomach
STATISTICAL ANALYSIS
One-way Analysis of Variance tests with Dunnett's t-test
MORTALITY/CLINICAL OBSERVATIONS:
450 mg/kg: one high dose male was found dead on day 5 (cause notevident),
signs of intoxication:
450 mg/kg bw, male, female:lethargy, tremors, hunched posture, rough hair coats post dosing
BODY WEIGHT
was sign reduced (p</=0.05): male, week 2-5, 13 at 450 mg/kg bw andweek 6-12, 14 from 150 mg/kg bw; female, week 11 at 450 mg/kg bw
body weight gain was reduced (p</=o.05): male, week 1-3 at 450 mg/kg bw
and week 4-13 from 150 mg/kg bw; female, week 1 at 450 mg/kg bw
FOOD CONSUMPTION
was sign. reduced (p</=0.05): male: 50 mg/kg bw, week 1, 2, 9, 11, 12;
150 mg/kg bw week 3, 6, 8, 12, 13; 450 mg/kg bw week 1-4, 6-9, 11;female: 50 mg/kg bw, week 4, 150 mg/kg bw, week 4, 11, 450 mg/kg bw,
week1, 4, 6
CLINICAL PATHOLOGY
clinical chemistry, haematology and urinalyses parameters were notaffected by treatment
OPHTHALMOLOGY
treatment related lesions were not seen
ORGAN WEIGHTS
organ weights were not affected by treatment
PATHOLOGY
treatment-related gross and histomorphology lesions were not in evidence
NOAEL (female) = 150 mg/kg bw/day
NOAEL (male) = 50 mg/kg bw/day(1) valid without restriction
Critical study for SIDS endpoint(131)

Result:Reliability
Flag
05.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
LOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Sub-acutemouse
male/female
B6C3F1oral feed
28 dayscontinuously in dietno0, 300, 1000, 3000, 10000 or 30000 ppm (see freetext RM)
yes
ca. 300 ppm
other: see freetext ME1991
yesother TS: m-cresol, purity > 98 %Method:SIZE OF STUDY GROUP:
5 male and 5 female mice per group
TIME HELD BEFORE STUDY: 13-15 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into groups per sex
DIET: NIH-07 mouse ration
ANIMAL ROOM ENVIRONMENT:138

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Remark:Result:temperature: 72° +/-3° F, humidity: 50 % +/-15 %, Fluorescent light: 12
hrs/day, room air changes : 10-12 changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly, and at termination,
feed consumption by cage recorded twice weekly
NECROPSY AND HISTOLOGIC EXAMINATION:
necropsy and tissue collection performed for all animals. A complete
histopathologic examination was conducted on all control animals, allanimals in the highest dose group with at least 60 % survivors at study
termination, and all aninmals in higher dose groups inclusive of early
deaths. The following organs and/or tissues were included in complete
histopathological examinations, as well as any tissue masses, grosslesions, and associated regional lymph nodes: adrenals, aorta, bone(sternebrae, femur, or vertebrae, including marrow), brain, bronchi, clitoral
gland, epididymis, oesophagus, gallbladder, heart, kidney, large intestines(caecum, colon, rectum), liver, lungs, lymph nodes (mesenteric), mammary
glands, nasal cavity and turbinates, oral cavity, ovaries, pancreas,parathyroids, pharynx, pituirary, preputial gland, prostate, salivary glands,
scrotal sac, seminal vesicles, skin, small intestine (duodenum, ileum,jejunum), spleen, stomach, testes, thymus, thyroid, tongue, trachea, tunica
vaginalis, urinary bladder, uterus and Zymbal's glands. Target organs andgross lesions were examined at lower doses until a no-observed chemical
effect was determined. Target organs included the following: uterus andovaries and mammary gland. Organ weights recorded for brain, liver, rightkidney, thymus, heart, and lungs of all animals, and the right testis of all
males.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test
mean compound consumption (mg/kg bw/day):males
females0 ppm
00300 ppm
53
661000 ppm
193
210
3000 ppm
521
651
10000 ppm
1730
2080
30000 ppm
4710
4940
mortality:
0 ppm: 1/5 male; 10000 ppm: 1/5 females; 300000 ppm: 2/5
males, 2/5 females;
Signs of toxicty:
at 30000 ppm: male, female;hunched posture, rough hair coat, thin appearance, lethargy andtremor,hypothermia (only females),at 10000 ppm: males and females, hunched posture, rough hair coat,females only: laboured respiration lethaty, sunken eyes
final mean body weight reduced at 30000 ppm in males (p</=0.01) and infemales (p</=0.05)
at study termination organ weights (w) were sign. increased:
liver: male rel. w. from 3000 pp. (p</=0.05), female, rel. w. from 300 ppm(p</=0.05); right kidney: male, rel. w. at 3000 ppm, female rel. w. at 30000
ppm (p</=0.05); brain: male, rel. w. at 30000 ppm (p</=0.01).
No histopathologic changes were reported from these organs.
histopathological evaluation,characterized by average severity score basedon a scale of 1 to 4 (1=minimal, 2=mild, 3=moderate, 4=marked), revealed
effects:
30000 ppm: female, moderate mammary gland atrophy, mild ovary atrophy
and moderate uterus atrophy
LOAEL (female) = 300 ppm (66 mg/kg bw/day), based on the increase inrelative liver weight
NOAEL (male) = 1000 ppm (193 mg/kg bw/day)

UNEP PUBLICATIONS

139

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
Method

:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

ResultReliability::(1) valid without restriction
Critical study for SIDS endpoint
(130)
mouse
femaleother: CBA/J
dermal6w
3 times/week
6 months
0.5 % in acetone
yesother: 5 rats, application of the substance to depilated or clipped lower
back by mist spray; observation of the hair colour of the new hair regrowth
were made weekly
1974
no dataother TS: no data on purity
No depigmentations of the regrowthed hair were observed.
(4) not assignablespecial study

18.09.2002
5.5

(132)

GENETIC TOXICITY ‘IN VITRO‘

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Sister chromatid exchange assay
human lymphocytes
0 -1.0 mM
no datano datanegative
other: see freetext ME
1986
no dataother TS: purity: 99.2 %Method:Remark:Reliability:

Lymphocyte fraction from healthy donors were grown in Medium 199 with
Earles salts. After 24 hrs of cultur m-Cresol diluted in DMSO was added for
88-90 hrs.
Positive control: Styrene-7,8-oxide
Statistical Method: Linear regression analysis
Results of the positive control or solvent control in comparison to p-cresol
were not given.
(2) valid with restrictions
Study description suffers from deficiencies: no information aboutcytotoxicity and wether a metabolic activation system was used or not, only
summary results given(133)

05.02.2004
Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result

140

:
:
:
:
:
:

Ames test
Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538
up to 2 mg/plate (solubility limit); vehicle: water
not cytotoxic
with and without

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Method:Year
GLP
Test substance:::

Remark:Reliability:

17.12.2002

other: according to Ames,Proc.Natl.Acad.Sci.70, 2281(1973);
Mutat.Res.31,347(1975);
Nestmann,Cancer Res.39.4412(1979); Environ.Mutagen.1,361(1979)1980
no dataother TS: m-cresol from commercial source (Aldrich)
According to the authors the result was "presumably negative, but solubility
did not allow the testing of the compound in amounts that result in bacterial
toxicity"
Metabolic activation: with and without (liver S-9 mix from Aroclor 1254
induced rats)(2) valid with restrictions
limited documentation
(134)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Ames test
Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537
no data

Reliability:(4) not assignable
documentation insufficient for assessmentwith and without
negative
other: according to Ames, Mutation Res. 31, 347 (1975)1980
no dataother TS: no data on purity

20.09.2002

(135)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Unscheduled DNA synthesis
rat primary hepatocytes
502, 251, 100, 50.2, 25.1, 10.0, 5.02, 2.51, 1.0, 0.502 ug/ml in DMSO
concentration range: 502 - 25.1 ug/ml: excessive toxicity
without
negative
other: OECD Guide-line 482, see freetext ME with additional informations
1988
yesother TS: m-cresol, purity: 99.8 %Method:Result:Reliability
Flag
06.02.2004::

DOSE SELECTION: Doses were chosen following a preliminary
experiment
SOLVENT: DMSOCONTROLS: solvent and 1-acetylaminofluorene (2-AAF) served as
negative and positive controls, respectively
EVALUATION CRITERIA: a dose related increase of at least 6 grains per
nucleus after subtraction of the concurrent negative control value
m-Cresol was evaluated as not causing UDS in cultured rat hepatocytes.
The positive control was functional.
(1) valid without restriction
Critical study for SIDS endpoint
(136)

Type
System of testing
Test concentration:::

Cycotoxic concentr.
Metabolic activation::

Sister chromatid exchange assay
cultured male human fibroblasts
0, 0.08, 0.8, 4, 8 mM dissolved in ethanol; 10, 30 mM dissolved in Eagle's
Minimal Essential Medium (MEM)> 8 mM cytotoxic response
without

UNEP PUBLICATIONS141

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Result
MethodYear
GLP
Test substance

:
:
:
:
:

negative
other: see freetext ME
1984
no dataother TS:m-cresol, purity: > 99 %Method:Remark:Reliability:

Flag
06.02.2004:

m-Cresol was added to the cells and incubated, in
triplicate, at 37 C for 2 hours. Following exposure, the cells were washed,reincubated in the absence of the test chemical for 48 hours, harvested
and SCE frequency and cell-cycle kinetics analysed
SOLVENT: m-Cresol was dissolved in
95% ethanol at concentrations up to and including 8 mM andin Eagle's minimum essential medium (MEM) at concentrations above this.
CONTROLS: 95% Ethanol and mitomycin C were used as negative andpositive controls respectively.
EVALUATION CRITERIA: positive if a dose-dependant significant incrase
in SCE frequencies compared to control is observed..
STATISTICAL ANALYSIS: Dunnett's test
m-Cresol did not induce significant increases over the control SCE
frequencies. The positive control was functional.
m-Cresol caused a small but statistically significant
decrease in cell-cycle progression at 8 mM (864 mg/l) andabove, indicative of a small cytotoxic response(2) valid with restrictions
only tested in the absence of metabolic activation and no information on
GLP
Critical study for SIDS endpoint
(137)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability:

other: DNA amplification
SV40-transformed CHO cell
5.0 mM in DMSO
without
negative
other: cells were incub. for 4d with m-cresol, then viability of the cells wasdetermined, SV40-DNA content was detected by hybridization according toLavi,Proc.Natl.Acad.Sci. (USA)80,6144,1981;Winocour,Proc.Natl.Acad.
Sci.(USA)77,48
1989
no dataother TS: purity: 98 %(4) not assignablespecial study

24.09.2002

(138)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

other: SV40 Mammilian Inductest
Syrian hamster kidney cells (SV40)
0.0001-0.0000001 ml

RemarkReliability::

Mammalian inductest(4) not assignablespecial test

142

without
positive
other
1983
no
no data

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

24.09.2002

(139)

Type
System of testing::

Test concentration
Cycotoxic concentr.
Metabolic activation
Result
Method

:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

Ames test
Salmonella typhimurium TA 100, TA 1530, TA 1535, TA 1538,TA 1950, TA
1951, TA 1952, G 46
0.5 % in ethanol
no dataambiguous
other: according to Ames Mutat. Res. 31,347 (1975); Science 176, 47(1972)
1975
no dataother TS: no data on purity
a questionable effect was produced in
the strain TA 1535
(4) not assignable
documentation insufficient for assessment

20.09.2002

(140)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability:

other: SOS-Chromotest
Escherichia coli PQ37
no datawithout
positive
other: After termination of the nitrosation of m-cresol with ammonium
sulphamate, test was performed according to Quillardet, Mutat. Res.
147,65 (1985)1989
no dataother TS: no data
(4) not assignable
documentation insufficient for assessment

24.09.2002

(141)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

other: Prophage induction assay
Escherichia coli / Bacteriophage lambda

Reliability:(4) not assignable
abstract only

positive20.09.2002
Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
Method
Year

(142)
:
:
:
:
:
:
:
:

Cytogenetic assay
Allium cepa
without
negative
1948

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m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

GLP
Test substance::noother TS: no data on purity

RemarkReliability::

marginal effects(4) not assignable
documentation insufficient for assessment

20.09.2002

(143)

Type
System of testing
Test concentration:::

Cycotoxic concentr.
Metabolic activation
Result
Method

:
:
:
:

Year
GLP
Test substance:::

Method:Result:Reliability:

Flag
06.02.2004:

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Cytogenetic assay
Allium cepa
0, 0.015, 0.02 and 0.025 % in destilled water
no datano datapositive
other: treatment period: 0: 3 hrs; 0.015 24 hrs; 0.02: 5 hrs; 0.025: 5 hrs
1965
noother TS: no data on purity

Reliability:(4) not assignable
documentation insufficient for assessment

Mouse lymphoma assay
L 5178 Y (TK +/-) cellswith and without S9-mix: 52.0, 78.0, 104, 156, 260, 312, 416, 520 ug/ml in
DMSOwith and without S9-mix: 520 ug/ml;
with and without
negative
other: similar to OECD Guideline 476, No differentiation between large andsmall colonies, see also freetext ME
1988
yesother TS: m-cresol, purity: 99.8 %S9-MIX of rat liver was used as metabolic activation system
SOLVENT: DMSOCONTROL: DMSO and ethylmethane sulfonate, 3-methylcholantrene
served as negative and positive cotrol, respectively
EVALUATION CRITERIA: a solitive response was indicated by a > two-foldincrease of mutant frequency over the concurrent background frequencies
m-cresol was evaluated as nonmutagenic in the mouse lymphoma cellsystem.
The positive controls were functional(2) valid with restrictions
no differentiation between small and large colonies, statistical evaluation
not mentioned
Critical study for SIDS endpoint(144)

20.09.2002
Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

144

(145)
:
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:

Ames test
Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538
0, 0.5, 5, 50, 500, 5000 ug/plate dissolved in DMSO
5000 ug/platewith and without
negative
other: see freetext ME
1982
no dataother TS: m-cresol, purity: 98 %UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Method:RemarkReliability
Flag
06.02.2004

:
:
:

Type
System of testing
Test concentration
Cycotoxic concentr.

:
:
:
:

Metabolic activation
Result
Method

:
:
:

Year
GLP
Test substance:::

Method:RemarkReliability

:
:

Flag
06.02.2004:

Type
System of testing
Test concentration:::

Cycotoxic concentr.

:

Metabolic activation
Result
Method

:
:
:

Year
GLP
Test substance:::

Method:Plate incorporation assay according to Ames, Mutation Res. 31, 347(1975),
S9-MIX: of Aroclor pretreated rat liver
SOLVENT: DMSOCONTROL: DMSO and sodium azide, 2-nitrofluorene, 9-aminoacridine, 2amino anthracene served as negative and positive control
DATA EVALUATION: Significance level for positive dose-response effects
were obtained with the Joncheere test
STATISTICAL ANALYSIS: Joncheere test
The positive controls were functional(1) valid without restriction
Critical study for SIDS endpoint(146)
Ames test
Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537
0.0, 3.3, 10.0, 33.0, 100.0, 333.0 ug/plate in water as solvent
to select dose range the chemical was checked for toxicity to S. typh. TA
100 (details not given)
with and without
negative
other: preincubation methodology according to Ames, Mutat. Res. 31,347(1975) and Yahagi, Cancer Lett. 1,91 (1975); see also freetext ME
1983
no dataother TS: m-cresol, purity: 97 %SOLVENT: water
S9-MIX: prepared from male Syrian Hamster liver anf from male spragueDawley rat liver, that were injected with Arocolor 1254:
CONTROL: water and : 2-aminoanthracenen, 4-nitro-o-phenylene diamine,
sodium azide, 9-aminoacridine served as negative and positive control;
DATA EVALUATION: oisitive response was indicated by a reproducable,
dose-related increase wether it be twofold over tthe background or not
STATISTICAL METHODS: based on the models presented by Margolin
the positive controls were functional(2) valid with restrictions
only 4 strains of Salmonella typhimurium were used
Critical study for SIDS endpoint(147)
Cytogenetic assay
Chinese Hamster Ovary (CHO) cells
without S9-mix: (1)+(2): 198, 297, 398, 495 ug/ml DMSO ; with S9-mix:(1)+(2): 250, 500, 749, 999 ug/ml, (3) 699, 749, 799, 898, 998, 1100 ug/ml
DMSO
Preliminary rangefinding assays were performed with and without
metabolic activation to determin cytotoxicity: >=898 ug/ml: toxic
with and without
negative
other: preliminary range finding studies; in accordance with OECD
Guideline 473, see also freetext ME
1988
yesother TS:m-cresol, purity: 99.8 %Duplicate CHO cultures were incubated for 17.2 hrs with 198-495 ug/ml of
the test substance in the nonactivation aberrations assay.
The metabolic activation cultures were treated with 250-1100 ug/ml of thetest substance for 2 hours

UNEP PUBLICATIONS

145

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
Solvent: DMSOCONTROL: DMSO and Mitomycin C, cyclophosphamide served as
negative and positive control, respectively
STATISTICAL ANALYSIS: Fisher's Exact Test with an adjustment for
multiple comparisons
The positive controls were functional(1) valid without restriction
Critical study for SIDS endpoint

RemarkReliability
Flag
06.02.2004

:
:
:

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
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:
:

Unscheduled DNA synthesis
other: Syrian Hamster Embryo (SHE) cells
1, 3, 10 uM, vehicle: medium
not determinedwith and without
positive
other: according to OECD Guide-line 482: not tested up to cytotoxicity
2000
no dataother TS: m-cresol, purity: >=98 %Result:Reliability:

Flag
06.02.2004:

A dose-dependent positive result was only obtained when tested in thepresence of a metabolic activation system. It was not tested up tocytotoxicity.
(2) valid with restrictions
not tested up to cytotoxic concentration, no data on GLP, no positive or
negative controls reported
Critical study for SIDS endpoint
(149)

5.6

(148)

GENETIC TOXICITY ‘IN VIVO‘

TypeSpecies
Sex
StrainRoute of admin.
Exposure period
Doses
Result
Method

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Year
GLP
Test substance:::

Remark:Result:146

Cytogenetic assay
other: mouse bone marrow cells
male/female
ICR
gavageonce
0, 96, 320, 960 mg/kg bw in corn oil
negative
other: in accordance with OECD Guideline 475, 5 mice/sex/dose, bonemarrow cells, sacrifice 6,24,48 hrs post treatment, negative and positive
controls, stat. method: Kruskal-Wallis test
1989
yesother TS: m-cresol, purity: 99.8 %dose finding study: see chapter 5.1.1
CONTROL: corn oil and cyclophphamide served as negative and positive
control
EVALUATION CRITERIA: positive response is indicated by statisticallysignificant dose-related increase in the number of structural aberrattions at
3 dose levels
The treatment did not increase the frequency of chromosomal aberrations,indicating that m-cresol was not clastogenic under the conditions of thisassay. The positive control was functionalmortality: 3/5 male mice in the 960 mg-group
signs of toxicity:
960 mg-group: within 10 min after dosing: squinty eyes, scruffy coats, mild
tonic convulsions and rapid breathing which ceased after 30 min.,

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
breathing difficulties
320 mg/kg bw: slightly scruffy coats within 22 hours after dosing
96 mg/kg bw: no signs of toxicity(1) valid without restriction
Critical study for SIDS endpoint

Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Doses
Result
MethodYear
GLP
Test substance

:
:
:
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:
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:
:
:

Sister chromatid exchange assay
mouse
male
DBA
i.p.
single application
0, 200 mg/kg bw dissolved in sunflower oil
negative
other: see freetext ME
1984
no dataother TS: m-cresol, purity: 99 %Method:Result:Reliability:

m-Cresol was administered to 2 or 3 intact or hepatectomized male miceby single intraperitoneal injection. After 30 min, DNA labelling was initiatedusing BrdU. After a further 21 hr the animals were killed, cells isolated andharvested and sister chromatid exchange (SCE) frequency in bone marrowcells, alveolar macrophages and regenerating liver cells analysed. Someof the mice were partially hepatectomized to induce liver cell regeneration
NEGATIVE CONTROLS: 0.35 ml sunflower oil (4 intact and 5
hepatectomized male mice, bone marrow cells, alveolar macrophages, liver
cells)
Positive Control: 5 mg cyclophosphamide/kg bw (2 intact male mice, bonemarrow cells and alveolar macrophages)
STATISTICAL ANALYSIS: One way analysis of variance; Dunnett's test forcomparison
No increase in SCE frequencies in the intact mice as wellas in the partially hepatectomized mice.
The dose tested was overtly toxic to the mice, causing lethargy,
piloerection and lacrimation.
The positive control was functional(2) valid with restrictions
only one dose tested and no information on GLP
(137)

(150)

06.02.2004
5.7

CARCINOGENICITY

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
ResultControl group
MethodYear
GLP
Test substance

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mouse
femaleother: Sutter
dermal12 w (I) or 20 w (II)twice weekly
no25 ul of a 20 % (I) or 5.7 % (II) solution in benzene

Remark:Groups of 20-29 Sutter strain mice:

yes, concurrent vehicle
other: Initiation-promotion test (see remarks)
1959
noother TS: m-cresol, not specified further

UNEP PUBLICATIONS

147

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
I. method: initiator: single dermal appl. of 0.3 % DMBA in
acetone;m-cresol was applied as promotor to theback of each mouse
I. result: 14/29 mice (12/12 benzene control animals)
survived and in 50 % (0 % in control animals)
skin papillomas were found; no carcinomas weredetected
II.method: initiator: 0.3 % DMBA in benzene;
promotor: m-cresol was applied to the back ofeach mouse
II.result: 17/20 mice (18/20 benzene control animals)
survived and in 24 % (0 % in control animals)
skin papillomas were found; no carcinomas weredetected
m-cresol was evaluated as promotor(2) valid with restrictions
no data on purity, benzene a known carcinogen as solvent, high mortality
rate
Critical study for SIDS endpoint(151)

ResultReliability

:
:

Flag
06.02.2004:

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
ResultControl group
MethodYear
GLP
Test substance

:
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:

other: in vitro cell transformation assay

Method:Result:Reliability:

Flag
06.02.2004:

40CFR 795.285 (modified), preliminary clonal cytotoxicity test, performanceof the test according to Kakunaga, Int. J. Cancer 12, 463, 1973, without
metabolic activation, negative and positive controls
Meta-cresol did not induce cell transformation in this assay; cytotoxicity: 48
nl/ml(2) valid with restrictions
non-validated test system
Critical study for SIDS endpoint(152)

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
ResultControl group
Method

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Year

:

148

other: mouse BALB/c-3T3 cells

0.57 - 48 nl/ml culture medium
negativeyesother: see freetext ME
1988
yesother TS: m-cresol, purity > 99 %other: in vitro cell transformation assay
other: mouse BALB/c-3T3 cell

6 - 72 nl/ml culture medium
negativeyesother: preliminary cytotoxicity test, performance of the test according to
Kakunaga, Int. J. Cancer 12, 463, 1973, with metabolic activation
1988

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

GLP
Test substance

:
:

yes
other TS: m-cresol, purity > 99 %Result:Reliability:

Flag
06.02.2004:

m-cresol did not produce significant increases in the number oftransformed foci, cytotoxicty: 62 nl/ml(2) valid with restrictions
non-validated test system
Critical study for SIDS endpoint

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
ResultControl group
MethodYear
GLP
Test substance

:
:
:
:
:
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:
:
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:

other: in vitro cell transformation assay

RemarkResultReliability:::

abstract only
m-cresol induced cell transformation(4) not assignable
abstract
documentation insufficient for assessment(153)

other: Syrian Hamster embryo (SHE) cells

positive
other: no details reported
1987
no dataother TS: no data on purity

17.12.2002
5.8.1

(154)

TOXICITY TO FERTILITYType: Two generation study
Species: rat
Sex: male/female
Strain: Sprague-Dawley
Route of admin.
: gavage
Exposure period: 27 w
Frequency of treatm.
: once/d, 7 d/w
Premating exposure periodMale: 10 w
Female : 10 w
Duration of test
: 29 w
No. of generation:
studies
Doses: 0, 30, 175 or 450 mg/kg bw/d in corn oil
Control group: yes, concurrent vehicle
NOAEL parental: 30 mg/kg bw
NOAEL F1 offspring: ca. 175 mg/kg bw
Method: other: TSCA Health Effects Test Guideline for specific organ/tissue toxicity- Reproduction/Fertility effects (EPA, 1983), see also freetext ME
Year: 1989GLP: yes
Test substance: other TS: m-cresol, purity: 99.4 %Method:25 rats/sex/dose (F0) were administered m-Cresol in corn oil. Exposure
began 10 weeks prior to breeding and continued in the females throughout
mating, gestation and lactation.

UNEP PUBLICATIONS

149

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
25 randomly selected F1 pups/sex/dose were gavaged with the appropriate
concentration of m-cresol for 11 weeks and then bred to produce F2 litters(dosing was continued throughout mating, gestation and lactation)
F2 offspring was sacrificed at weaning.
reproductive indices: mating indices for males and females, fertility indicesfor males and females, gestational index, live birth index, 4-day survivalindex 7-day survival index, 21-day survival index, lactation index
Necropsy and pathology:
all F0 and F1 parental rats in all groups were subjected to a complete
necropsy ; 25 male and 25 female adults from the controls and from thehigh dose groups were subjected to histopathology examination: pituitary,
vagina, uterus, ovaries. testes, epididymides, seminal vesicles, prostateand other tissues with gross lesions identified as potentially treatment
related; any of thze above organs or tissues showing gross alterations
were also evaluated microscopically in other dose groups
A complete gross necropsy and histopathologic examination wereconducted for any parental rat dying on test
Gross necropsy included examination of the external surfaces, all orificwes,
cranila cavity, carcass, external and cut surfaces of the brain and spinal
cord, the thoracic,abdominal and pelvic cavities and their viscera, cervicaltissues and organs
a gross internal examination on any F1 and F2 pup appearing abnormal or
dying on testA complete gross necropsy and histopathologic examinations
were conducted for any animals dying on test.

Result:statistical methods:
Levene's test,ANOVA, t-test corrected by Bonferroni method, KruskalWallis test, Mann Whitney U-test, Fishers exact test
F0: pre-breed dosing period:
450 mg/kg: f,m: significant reduced body weight, signs of
toxicity: hypoactivity, ataxia, twitches, tremors,
prostration, unkempt appearance(males), urine stains,
audible respiration perinasal encrustration and perioral
wetness; mortality: 7/25 m, 5/25 f;
175 mg/kg: sacrifice due to trauma 1/25 m
F0: breed period:
450 mg/kg: maternal gestat. and lactat. bw sign. reduced,
mortality: 450 mg/kg:2/20 f; 175 mg/kg: 1/25 f;
reproductive parameters including gestational length were
unaffected by treatment
F1:
litter size, sex ratio, litter viability, pup survival were
unaffected by treatment; 450 mg/kg: reduced female pup bw
F1 pre-breed period:slightly reduced bw in m (450, 175,30 mg/kg) and in f (450,30 mg/kg);
signs of toxicity: 450 mg/kg bw: hypoactivity, ataxia twitches, tremors
prostration urine stains, audible respiration and perioral wetness (also at
175 mg/kg
females); mortality: 450 mg/kg 3 m and 4 f;
F1 breed period:
450, 175, 30 mg/kg: reduced bw in m; maternal gestational
and lactational bw reduced in 450 mg/kg f; mortality during
gestation: 1 f each at control, 30, 175 mg/kg and 3 f at 450 mg/kg, mortality
during lactation: 3 f at 450 mg/kg
Reproductive parameters including gestational parameters
were unaffected by treatment
F2:
litter size and sex ratio unaffected; F2 pup lactational

150

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
index was reduced at 450 mg/kg
450 mg/kg: pup bw and pup bw gain was reduced and pup deaths
increased.
Pathology:
all groups: there were no treatment related gross lesions or
histologic lesions in F0, F1 and F2 rats which survived toscheduled sacrifice.
dead prior to schedule: F0,F1 m: lesions in brain , thymic
regions, lungs, decrease in number of sperm in epididymides,
atrophied seminal vesicles and coagulation glands,
epididymitis; F0,F1 f: lesions in the brain, lungs
NOAEL (fertility): 450 mg/kg bw
The exact A/D ratio cannot be calculated. But it can beassumed that the A/D ratio would be less than 1 (<30.0 mg/kg
bw/day/175.0 mg/kg bw) indicating no increased risk tooffspring in the absence of parental toxicity.

Reliability
Flag
06.02.2004
5.8.2

:
:

A/D ratio: exposure level at which there were no observableeffects in adults/the exposure level at which there were noobservable effects in offspring(1) valid without restriction
Critical study for SIDS endpoint(155)

DEVELOPMENTAL TOXICITY/TERATOGENICITY

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
NOAEL maternal tox.
NOAEL teratogen.
Result
Method

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Year
GLP
Test substance:::

Method:rat
femaleSprague-Dawley
gavageday 6 through day 15 of gestation
daily
until gd 21
0, 30, 175 or 450 mg/kg bw/d dissolved in corn oil
yes, concurrent vehicle
ca. 175 mg/kg bw
ca. 450 mg/kg bw
see freetext RS
other: following the TSCA Health Effects Test guidelines for SpecificOrgan/Tissue Toxicity - Developmental Toxicity (EPA, 1984,1987)
1988
yesother TS: m-cresol, purity: 99.4 %Dose selection was based on the results of a range-finding study.
Solvence: corn oil
25 mated females/group, 50 control females, all females were weighed ond
gd 0, 6, 11, 15, and 21, food consumption was measured throughout
gestation, all females were examined daily for clinical signs, for mortality
and morbidity
sacrifice on gd 21:
does were evaluated for body weight, liver and gravid uterine weight,
number of corpora lutea and number of status of implantation sites (i.g.
resorptions, dead fetuses, live fetuses)
live fetuses were dissected from uterus, counted and weighed, examinedfor external malformations and variations, and for visceral malformaltionsand variations, and for soft tissue craniofacial malformations
statistical analysis:
Levene's test, ANOVA, pooled t-test, Kruskal-Wallis test, Mann-Whitney U-

UNEP PUBLICATIONS

151

OECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004
test, Fisher's exact test
maternal toxicity:
no deaths, no abortions or early deliveries
450 mg/kg:
significant reduced food consumption, reduced maternal body weights andweight gain during dosing period; reduced gestational weight gain (day 021);
clinical signs of toxicity: hypoactivity, ataxia, tremors, audible respiration,
perioral wetness;increased relative but not absolute liver weights no embryotoxicity or
teratogenicity was observed at any
dosage level(1) valid without restriction
Critical study for SIDS endpoint(156)

Result:Reliability
Flag
06.02.2004::

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group

:
:
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:
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:
:

rabbitfemaleNew Zealand whitegavageday 6 through day 18 of gestation
once daily
until day 29 of gestation
0, 50, 150, 300 or 500 mg/kg bw/dyesRemark:Result:Reliability:

8 rabbits/dose
range-finding study
50 mg/kg: one doe aborted; ataxia, twitching, gasping,
audible, labored and rapid respiration;
increased relative liver weights
150 mg/kg: maternal mortality 2/8; reduced foodconsumption o gd 7-9; significantly
depressed body weight gain for gd 6-12;
cleft palace in 1 fetus>= 300 mg/kg:reduced food consumption on gd 6-10;
significantly elevated clinicals signs of
toxicity (CNS and cardiopulmonary categories;
see at 50 mg/kg)
300 mg/kg: maternal mortality 1/8; one doe aborted;
reduced body weight on gd 12 andsignificantly depressed body weight gainon gd 6-12; increased preimplantation loss
and increase in dead fetuses/litter;
forelimb and pectoral girdle anomalies in
4 fetuses in 2 litters; cleft palate in
1 fetus; small tongue
500 mg/kg: maternal mortality 8/8(2) valid with restrictions
dose range finding study

12.11.2002
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group

152

(157)
:
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:
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:

rabbitfemaleNew Zealand whitegavageday 6 through day 18 of gestation
once daily
until day 29 of gestation
0, 5, 50 or 100 mg/kg bw/day
yes, concurrent vehicle

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

NOAEL maternal tox.
NOAEL teratogen.
Method

:
:
:

Year
GLP
Test substance:::

Method:Result:Reliability
Flag
06.02.2004::

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group

:
:
:
:
:
:
:
:
:

rat
femaleWistars.c.
day 7 through day 17 of gestation
daily
until post partum
90 mg/kg bw/d (30 ml/kg bw 0.3 %)yes

Result:Reliability:

m-cresol was used as the solvent at a concentration of 0.3%; no negative effects on F0- or F1-generation were observed
when compared with control animals.
(3) invalid
application route is not relevant for the human situation

ca. 5 mg/kg bw
ca. 100 mg/kg bw
other: following the TSCA Health Effects Test guidelines for SpecificOrgan/Tissue Toxicity - Developmental Toxicity (EPA, 1984,1987)
1988
yesother TS: m-cresol, purity: 99.7 %Dose selection was based on the results of a range-finding study.
14 mated females/group, 28 control females, all females were weighed ond
gd 0, 6, 12, 18, 24 and 29, food consumption was measured throughout
gestation, all females were examined daily for clinical signs, for mortality
and morbidity
sacrifice on gd 29:
does were evaluated for body weight, liver and gravid uterine weight,
number of corpora lutea and number of status of implantation sites (i.g.
resorptions, dead fetuses, live fetuses)
live fetuses were dissected from uterus, counted and weighed, examinedfor external malformations and variations, and for visceral malformaltionsand variations, and for soft tissue craniofacial malformations
statistical analysis:
Levene's test, ANOVA, pooled t-test, Kruskal-Wallis test, Mann-Whitney Utest, Fisher's exact test>= 50 mg/kg: audible respiration and ocular discharge
No embryotoxicity or teratogenicity was observed at any
dosage employed.
(1) valid without restriction
Critical study for SIDS endpoint(158)

12.11.2002(159)

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group

:
:
:
:
:
:
:
:
:

rat
femaleWistars.c.
day 17 of gestation until 21 days after birthdaily
until 8 w post partum
90 mg/kg bw/d (30 mg/kg 0.3 %)yes

Result:m-cresol was used as the solvent at a concentration of 0.3%; no negative effects on F0-, F1- or F2-generation wereobserved when compared with controls (no fetotoxicity,normal postnatal development, normal behaviour and

UNEP PUBLICATIONS

153

OECD SIDS
5. TOXICITY

Reliability

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:

fertility).
(3) invalid
application route is not relevant for the human situation

12.11.2002(160)

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group

:
:
:
:
:
:
:
:
:

Mouse
Femaleother: ICR-SLC
s.c.
day 6 through day 15 of gestation
Daily
until 5 w post partum
no data
Yes

Result:Reliability:

m-cresol was used as the solvent; no signs of fetotoxicity
or teratogenicity, no maternal toxicity.
(3) invalid
application route is not relevant for the human situation

12.11.2002(161)

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group

:
:
:
:
:
:
:
:
:

RabbitFemaleno datas.c.
day 6 through day 18 of gestation
Daily
until >= 12 d after exposure
30 mg/kg bw/d (10 ml/kg 0.3 %)Yes

Result:Reliability:

m-cresol was used as the solvent at a concentration of 0.3%; decreased maternal food consumption and body weight gain
after day 14 of gestation, increased average number of
implantations and reduced mean body weights in male
fetuses, no increase of anomalies.
(3) invalid
application route is not relevant for the human situation

12.11.2002
5.8.3

(162)

TOXICITY TO REPRODUCTION, OTHER STUDIESType
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result
Method

:
:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance

:
:
:

154

Other
In vivoRatmale/female
other: Fisher 344/N
oral feed
28 dcontinuously in diet28 d0, 300, 1000, 3000, 10000, 30000 ppm
yes, concurrent no treatment
see freetext RS
other: the reproductive organs were examined as part of the 28-day study,
see chapter 5.4
1991
Yes
other TS: purity>98 %UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Result:Reliability
10.07.2002:

Type
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result
Method

:
:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability
10.07.2002:

Type
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result

:
:
:
:
:
:
:
:
:
:
:
:

Method:Year
GLP
Test substance

:
:
:

Other
In vivoRatmale/female
Sprague-Dawley
Gavage13 weeks
Daily
14 weeks
0, 50, 150, 450 mg/kg bw in corn oil
yes, concurrent vehicle
no effects on reproductive organs were reported, neither in males nor infemalesother: the reproductive organs were examined as part of the 13 week
study, see chapter 5.4
1986
Yes
other TS: m-cresol, purity: 98.6 %Reliability
Flag
06.02.2004::(1) valid without restriction
Critical study for SIDS endpoint

5.9

Histological evaluation , characterized by average severity score based ona scale of 1 to 4 (1=minimal, 2=mild, 3=moderate, 4= marked) revealed
effects:
uterine atrophy in 4/5 females at 30000 ppm(1) valid without restriction
(130)
Other
In vivo
Mousemale/female
B6C3F1oral feed
28 dcontinuously in diet28 d0, 300,1000, 3000, 10000, 30000 ppm
yes, concurrent no treatment
see freetext RS
other: the reproductive organs were examined as part of the 28 day study,
see chapter 5.4
1991
Yes
other TS: purity>98 %Histopathological evaluation, characterized by average severity scorebased on a scale of 1 to 4 (1=minimal, 2=mild, 3=moderate, 4=marked),
revealed effects:
30000 ppm: female, moderate mammary gland atrophy, mild ovary atrophy
and moderate uterus atrophy(1) valid without restriction
(130)

(131)

SPECIFIC INVESTIGATIONS

Endpoint:
Study descr. in chapter :Neurotoxicity

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ID: 108-39-4
DATE: 24.05.2004

Reference
Type
Species
Sex
StrainRoute of admin.
No. of animals
VehicleExposure period
Frequency of treatm.
Doses
Control group
Observation period
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Method:Result:Reliability:

Flag
05.02.2004

:

5.10

156

other: subchronicRatmale/female
other: CD
Gavage20
other: corn oil
90 day(s)Daily0, 50, 150, 450 mg/kg bw/day
yes, concurrent vehicle
13 weeks during dosing
see freetext RE
other: see freetext ME
1986
no dataother TS: no data on purity
10 male and 10 female CD rats/treatment group received corn oil solutionsof 50, 175 or 600 mg/kg bw /day by gavage once daily for 13 weeks. 20
male and 20 female CD rats received corn oil alond to serve ascontrol.Rats were observed for body weight gain, food consumption,clinical signs.
Signs of neurobehavioral toxicity were documented during pretreatment, 1
and 6 hours after dosing on study day 1 and prior dosing on study days 2,
7, 14, 30, 60 and 90 including salivation, urination, tremors, piloerection,
diarrhea, pupil size, pupil response, lacrimation, hypothermia, vocalization,
exophthalmus, palpebral closure, convulsions (type and severity),
respiration (rate and type), impaired gait, positional passivity, locomotor
activity, stereotypy, startle response, righting reflex, performance on a wire
maneuver, forelimb grip strength, positive geotropism, extensor thrust, limb
rotation, tail pinch reflex, toe pinch reflex, hind limb splay.
gross and histopathologic examination
Mortality: control: 1 female (2.5 %), 450 mg-gr: 1 female (5 %), gross andhistopathologic examination: aspiration or inhalation of the TS, pulmonaryedema
body weight gain comparable to control
mean food consumption, 450 mg-gr., males and females: significantly lessthan control during the initial portion of the study
clinical signs: dose related in incidence: salivation, myotonus, tremors,urine wet abdomen, hypoactivity, rapid respirationneurobehavioral toxicity:
450 mg-group, males and females: initial part of the study: incidence of
palpebral closure, rales, laboured respiration; at study termination, females:significantly increased urination.
Other differences from controls with regard to behavioral tests were
evaluated as sporadic in nature by the authors (no further details given).
necropsy:brain weights of treated animals comparable to controls; gross andmicroscopic examination of tissues revealed no lesions which were
attributable to treatment(2) valid with restrictions
limited documentation (only study summary available)
Critical study for SIDS endpoint(163) (112) (164)

EXPOSURE EXPERIENCEUNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Remark:Reliability
14.01.2003:

RemarkReliability
Flag
14.01.2003:::

Remark:Reliability
15.01.2003:

Remark:Reliability
15.01.2003:

Remark:Reliability
Flag
14.01.2003::

Remark:In humans, m-cresol may be excreted as a metabolite in urine
after occupational exposure to phenols, cresols, xylenols,
naphthalene and/or toluene.
(4) not assignable(165) (166) (167) (168) (169) (170) (171)The probable oral lethal dose for humans is 50-500 mg/kg.
(2) valid with restrictions
Critical study for SIDS endpoint(172)
In humans, insulin preparations with m-cresol resulted in an
impaired leukocyte function (decreased killing capacity ofhuman polymorphonuclear leukocytes (PMNL), expressed as thepercentage of Staphylococcus aureus killed after 60 minutesof incubation). m-cresol is possibly implicated in thepathogenesis of local infections in continuous subcutaneous
insulin infusion(4) not assignable(173)
Case report: A 44-y-old male was found unconscious afteringestion of 300 ml of 50 % cresol-soap solution.
Endotracheal intubation, gastric lavage and activatedcharcoal reversed his conscious. He had dermal burns,
oesophageal and gastric erosions, pneumonia, mixed metabolic
acidosis and respiratory alkalosis, renal and liver function
impairment, leucocytosis and dark urine. Acute renal failureand hemolysis developed, but recovered after hemodialysis
and intensive supportive care.
Urine levels of p-,m-,o-cresol and phenol were resp. 2083,
2059, 125 and 68 mg/g creatinine at 7 h post ingestion.
The patient recovered.
(4) not assignable(174)
case report: Accidental dermal exposure of both legs and face of a 47year-old man resulted in corrosion of 15 % of his body surface and hedeveloped acute polyuric renal failure. Serum levels of m-cresol after 1 h
were above 30 mg/l.
After 5 hemodialysis procedures renal function recovered.
Levels of m-cresol in the dialysate were less than 5 % of
the levels in serum. Hemodialysis had no significant effecton the serum concentration time course of m-cresol.
(2) valid with restrictions
Critical study for SIDS endpoint(175)
The Agency for Toxic Substances and Disease Registry (ATSDR)
Minimal Risk Levels (MLR) were developed to provide
screening levels for health assessors and other responders
to identify contaminants and potential health effects that
may be of concern at hazardous waste sites an releases. An
MRL is an estimate of the daily human exposure to ahazardous substance that is likely to be without
appreciable risk of adverse noncancer health effects over a

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m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability
15.01.2003:

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability:

Flag
14.01.2003:

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
15.01.2003::

Remark:158

specific duration of exposure:m-cresol: MRL = 0.05 mg/kg bw/d acute oral exposure(4) not assignable(176)
It is reported that certain individuals are hypersensitive tocresol (isomer not specified, no further information)(4) not assignable
Critical study for SIDS endpoint(110)
Case reports: intentional or accidental oral intake of cresols (all isomers):
irritation of mouth and throat, abdominal pain, vomiting, hemolytic anemia,
increased heart ratem liver and kidney damage, headaches, facial
paralysis, drowsiness, cramps coma and death(2) valid with restrictions
description suffers from deficiencies as the isomers are not specified
Critical study for SIDS endpoint(177) (178) (179) (180)Skin depigmentation (chemical leukoderma has been reported after local
exposure to cresols (isomer not specified)(4) not assignable
Critical study for SIDS endpoint(130)
It is reported that skin contact has alo resulted in effects on the nervous
system, liver and kidneys and caused human fatalities.
(4) not assignable
Critical study for SIDS endpoint(179)
A cresol solution, unintentionally poured over the trunk, caused grosshematuria, gastrointestinal bleeding, hypertension and septic shock withsevere jaundice and renal failure.
(2) valid with restrictions
Critical study for SIDS endpoint(181)
The development of tumours in persons who had been exposed
occupationally to cresol (unspecified isomer) has been reported, and twocases of transitional cell bladder carcinoma were described after longterm
exposure to cresol. Since no information on exposure levels are available
and since co-exposure to other substances cannot be excluded a
carcinogenic potential of the cresol isomers cannot be deduced fron thesecases.
(2) valid with restrictions
Critical study for SIDS endpoint(182)
Case report: a worker in an oil rafinery was exposed to cresol,
dichlorooctane and chromic acid for a long period developed a squamous
epithelial carcinoma of the vocal cords. Since no information on exposurelevels is available and since co-exposure to other substances is included a

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
05.02.2004

:
:

5.11

carcinogenic potential of the cresol isomers cannot be deduced from thiscase report.
(4) not assignable
Critical study for SIDS endpoint(179)
Anomalous menstrual cycles were found and hormonal disorders werereported from women who were employed in ther production to enamelledwire or of tricresyl phosphate and were exposed to a variety ofcompounds, including chlorobenzenes and phosphoryl chloride. It wasclaimed that the incidence of perinatal child death was increased and thatdevelopmental disorders were frequent among new-born babies. since nodata on exposure levels and duration of exposure are given and data on
controls were not provided a relationship between the described effects
and cresol exposure cannot be deduced.
(4) not assignable
Critical study for SIDS endpoint(179)

ADDITIONAL REMARKS

Type

:

Cytotoxicity

Remark:Reliability
16.01.2003:

m-cresol (test concentration: 0, 2, 5, 10, 20
or 50 ppm; test duration: 66 h) showed a concentration
dependent decrease in growth rate and cell yield in L-M
strain cells (CCL 1.2; derived from NCTC clone 939 mouse
fibroblast line) in suspension culture. No effect wasobserved with 2 ppm.
(4) not assignable

Type

:

Cytotoxicity

Remark:Reliability
16.01.2003:

Cytotoxicity assay, V79 cells: the growth of
V79 cells was inhibited in a dose- and time-related manner,
while DNA-, RNA- and protein-syntheses were inhibited in adose-related fashion.
(4) not assignable

Type

:

Metabolism

Remark:Reliability
16.01.2003:

In male Wistar rats, m-cresol was excreted as a metabolite
in urine after a single i.p. injection of 0.12 ml
14C-toluene/rat.
(4) not assignable

Type

:

Metabolism

Remark:Reliability
16.01.2003:

m-cresol was excreted as conjugated glucuronide in urine
when adminstered orally to one rabbit in a dose of 2000 mg
or one hen in a dose of 1000 mg.
(4) not assignable

Type

:

(183)

(184)

(169)

(185)
Metabolism

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m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Remark:Reliability
16.01.2003

:

Type

:

Metabolism

Remark:Reliability
16.01.2003:

The retention of m-cresol in male Wistar rats after theoral administration of 25 ug/rat for 3 d (test period 7 d)
was 0.2 % (percentage of applied dose).
(4) not assignable

Type

:

Metabolism

Remark:Reliability
16.01.2003:

After an oral application of 10 g m-cresol
within 3 days to one dog the substance was excreted
unchanged in urine.
(4) not assignable

Type

:

Metabolism

Remark:Reliability
16.01.2003:

In an in vitro study m-cresol was hydroxylated
to 2,5-dihydroxytoluene and probably to the sulfate
conjugate of m-hydroxybenzyl alcohol with rat liverhomogenate and slices.
(4) not assignable

Type

:

Metabolism

Remark:Reliability
16.01.2003:

in vitro: Metabolic cooperation assay for gap junctional
intercellular communication with chinese hamster cells(V79): negative.
(4) not assignable

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:160

In female CFY rats, the excretion of m-cresol in urine wasincreased after exposure to xylene (4000 mg/m3/6 h).
(4) not assignable
(186)

(26)

(187)

(188)

(189)
m-cresol inhibited the growth of chick embryo fibroblasts(incubation for 24 h), the sublethal dose was approx. 20
mg/l and the lethal dose > 20 < 50 mg/l.
(4) not assignable(78)
m-cresol (0.5 or 1.0 ml) showed an inhibitory effect on the
ATP-induced (50 ug) pulmonary vasoconstriction in isolated
perfused rabbit lungs.
(4) not assignable(190)
m-cresol (550 mg/m3) showed a ciliostasis index of 0.7 to
0.75 in isolated rabbit tracheal tissue.
(4) not assignable(191)
In a neutral red (NR) cytotoxicity assay with Bluegill
sunfish BF-2 cells, the NR50 was determined with 5.3 mM.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004

Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:In vitro short term cytotoxicity tests:

Reliability
16.01.2003:

I. method: inhibition of cell growth in ascites sarcoma
BP8 cells (concentration 1mM, incubation for
48 hours)
I. result: the inhibitory effect was >= 30 <= 39 %II. method: inhibition of oxidative metabolism in isolated
brown fat cells (concentration 1mM, incubationfor 5 min at 37 Grad C)
II. result: the inhibitory effect was >= 60 <= 69 %III. method: plasma membrane damage in human diploidembryonic lung fibroblasts (MRC-5, leakage
of a cytoplasmatic nucleotide marker fromprelabelled cells, concentration 25 mM,
incubation for 30 min at 37 Grad C)
III. result: the release was >= 30 <= 39 %IV. method: ciliotoxicity (ciliostasis in tracheas ofchicken embryos, concentration 5 mM, incubation
at 37 Grad C)
IV. result: the ciliotoxicity was >= 70 <= 79 %(4) not assignable

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:(4) not assignable(192)
In male Sprague-Dawley rats no effect on oxygen consumption
was observed after a single i.p. injection of 50-200 mg/kg
bw.
(4) not assignable(193) (194)(195)
In vitro study:
in isolated heavy beef heart mitochondria (HBHM), m-cresol
in a concentration of 3.6 x 10E-4 M was shown to stimulate
the HBHM NADH-oxidase system. In the HBHM succinoxidase
system, no effect was observed.
(4) not assignable(196)
m-cresol showed no antimutagenic effect on MNNG-induced
mutagenesis in E. coli WP2(4) not assignable(197)
Biochemistry: m-cresol at a concentration of 1 mM showed astimulation of prostaglandin synthesis (max. percent
increase: 268 +- 26), while a concentration of 10 mM showed
an inhibition of prostaglandin synthesis (percent
inhibition: 55 +-3.5).
(4) not assignable(198)
Increasing concentrations of m-cresol produced increasing
inhibition of thymidine incorporation in Hela cells.

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Reliability
16.01.2003

162

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004:(4) not assignable(105)

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(1)

Bayer AG, Product Specification, Technical Information m-Cresol (2000)(2)

Deutsche Forschungsgemeinschaft, MAK- und BAT-Werte-Liste
2001, Senatskommission zur Prüfung gesundheitsschädlicher
Arbeitsstoffe, Mitteilung 37, VCH Verlagsgesellschaft mbH,
Weinheim 2001.

(3)

Bayer AG, Safety data sheet, m-Kresol rein (2001-11-06)(4)

Lide, D.R. (Ed.), CRC handbook of chemistry and physics,
70st ed.. CRC Press Inc., Boca Raton, C-221 (1989)(5)

The Merck Index, 12th Edition. Ed. by Budavari et al.
Whitehouse Station, NJ (1996)(6)

Sax, N.I. & Lewis, R.J. (1987): Hawley's Condensed Chemical
Dictionary, 11th Edition. Van Nostrand Reinhold Company, New
York

(7)

Verschueren, K.: Handbook of Environmental Data on Organic
Chemicals. John Wiley & Sons Inc. (1996)(8)

Auer-Technikum, 12. Ausgabe. Auergesellschaft Berlin,
398-403 (1989)(9)

Lide, D.R. (Ed.), CRC handbook of chemistry and physics,
82st ed.. CRC Press Inc., Boca Raton, 3-257 (2001-2002)(10)

Daubert TE and Danner RP (1989) Physical and thermodynamic
properties of pure chemicals: data compilation, experimental data, cited in SRC-MPBPVP v
1.40

(11)

Hansch, C. et al.: Exploring QSAR. Hydrophobic, Electronic,
and Steric Constants. ACS Professional Reference Book.
Washington, DC: American Chemical Society (1995), experimental data, cited in SRCKowWin v.1.66(12)

Yalkowsky SH and Dannenfelser RM (1992) Aquasol database of
aqueous solubility. Version 5.; College of Pharmacy,
University of Arizona - Tucson, AZ. PC Version, experimental data, cited in SRC-WSKOW
v1.40

(13)

Bayer AG: study report 'Sicherheitstechnische
Daten/Produktbeschreibung von m-Kresol' (2000-08-14)(14)

Bayer AG (2002) Calculation of the predicted pKa of m-cresol ACD/ILab Web service(15)

Pearce PJ and Simkins RJJ (1968) Can J Chem 46, 241-248(16)Chuchani G and Frohlich A (1971) J Chem Soc (B): 1417-1419(17)Dietz F and Traud J (1978) GWF-Wasser/Abwasser 119, 318-325(18)

Bayer AG (2003): Calculation of indirect photodegradation with AOPWIN(19)

Semadeni M, Stocker DW, Kerr JA (1995) Int. J. Chem. Kinet. 27, 287-304(20)

Atkinson R (1994) J. Phys. Chem. Ref. Data, Monograph No.2: Gas-Phase Tropospheric
Chemistry of Organic Compounds

UNEP PUBLICATIONS

163

OECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(21)

Atkinson R and Aschmann SM (1990) Int. J. Chem. Kinet. 22:
59-67

(22)

Atkinson R (1987) Intern. J. Chem. Kinet. 19: 799-828(23)

Atkinson R, Darnall KR, Lloyd AC, Winer AM, Pitts JN (1979) Adv. Photochem. 11: 375488(24)

Atkinson R, Darnall, KR, Pitts, JN (1978) J. Phys. Chem. 82: 2759 - 2761

(25)

Koch R and Wagner BO (1989) Umweltchemikalien. VCH
VerlagsGmbH, Weinheim, 191-193(26)

Freitag D, Ballhorn l, Geyer H, Korte F (1985) Environmental Hazard profile of organic
chemicals. Chemosphere 14: 1589-1616(27)

Evangelista RA, Allen HL, Mandel RM (1990) J. Hazard. Mater. 25(3): 343-360(28)

Aelion CM, Swindoll CM, Pfaender FK (1987) Adaptation to and Biodegradation of
Xenobiotic Compounds by Microbial Communities from a Pristine Aquifer. Appl Environm
Microbiol 53: 2213-2217(29)

Hawthorne SB and Sievers RE (1984): Environ Sci Technol 18, 483-490. As cited in HSDB
(1993)(30)

Altschuh J, Brueggemann R, Santl H, Eichinger G, Piringer OG (1999) Henry's Law
Constants for a Diverse Set of Organic Chemicals: Experimental Determination andComparison of Estimation Methods. Chemosphere 39: 1871 - 1887

(31)

Boyd SA (1982) Soil Sci. 134(5): 337-343(32)

Bayer AG (2002): calculation of the environmental
distribution of m-cresol according to fugacity model Mackay
level I

(33)

Bayer AG (2002) Ready Biodegradability: Closed Bottle Test

(34)

Desai S, Govind R, Tabak H (1990) ACS Symp Ser 422: 142-156(35)

Wellens H (1990) Z Wasser Abwasser Forsch 23: 85-98(36)

Pitter P (1976) Determination of biological degradability of organic substances. Water
Research 10: 231-235(37)

Shelton DR, Tiedje JM (1981) Development of test for
determining anaerobic biodegradation potential. NTIS Report[PB 84-166495], Springfield(38)

Shelton DR, Tiedje JM (1984) Appl. Environ. Microbiol. 47: 850-857(39)

Battersby NS and Wilson V (1989) Appl. Environ. Microbiol. 55: 433-439(40)

Liu D, Pacepavicius G (1990) Toxicity Assessment 5 (4): 367-387(41)

Jensen BK, Arvin E, Gundersen, AT (1989) Biodegradation of phenolic compounds andmonoaromatic hydrocarbons by a mixed wastewater culture under denitrifying conditions.
In: Quaghebeur D, Temmermann I, Angeletti G (Ed.), Organic contaminants in waste
water, sludge and sediment: occurence, fate and disposal. London, 150-157(42)

Boyd SA, Shelton DR, Berry D, Tiedje JM (1983) Appl. Environ. Microbiol. 46: 50-54

164

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(43)

Fedorak PM and Hrudey SE (1984) Water Res 18: 361-7(44)

Roberts DJ, Fedorak PM, Hrudey SE (1987) Can. J. Microbiol. 33, 335-338(45)

Horowitz A, Shelton DR, Cornell CP, Tiedje JM (1982) Dev. Ind. Microbiol. 23, 435-444(46)Wang Y-T, Suidan MT, Pfeffer JT, Najam I (1989) Biotechnol. Bioeng. 33: 1353-1357(47)

Smolenski WJ and Suflita JM (1987) Appl. Environ. Microbiol.
53: 710-716(48)

Kaminski U, Kuschk P, Janke D (1990) J. Basic Microbiol. 30: 259-265(49)

Kondo M, Nishihara T, Shimamoto T, Koshikawa T, Ito T, Sawamura R, Tanaka K (1988)
Eisei Kagaku 34(2): 188-185(50)Arvin E, Jensen B, Godsy EM, Grbic-Galic D (1989) Microbial degradation of oil andcreosote related aromatic compounds under aerobic and anaerobic conditions. Int. Conf.
Physiochem. Biol. Detoxif. Hazard. Wastes 2: 828-847(51)

Ramanand K and Suflita JM (1990) Anaerobic biodegradation of
m-cresol in anoxic aquifer slurries and a sulfate reducing
bacterial enrichment. Abstracts Annu. Meet. Amer. Soc.
Microbiol. 90, 299(52)

Roberts DJ, Fedorak PM, Hrudey SE (1990) Appl. Environ. Microbiol. 56: 472-478(53)

DeGraeve GM, Geiger DL, Meyer JS, Bergman HL. (1980) Acuteand embryo-larval toxicity of phenolic compounds to aquaticbiota. Arch. Environ. Contam. Toxicol. 9: 557-568(54)

Howland, R.M.. Investigations in Fish Control 34, 1-10,
US Department of the Interior, Bureau of Sport Fisheries
and Wildlife (1969)(55)

Saarikoski J and Viluksela M (1982) Ecotox. Environ. Safety 6: 501-512(56)

Wellens H (1982) Z. Wasser Abwasser Forsch. 15: 49-52(57)

Falk-Petersen IB, Kjorsvik E, Lonning S, Moller Naley A, Sydnes LK (1985) Sarsia 70, 1116

(58)

Ruebelt C et al. (1982) Schadstoffe im Wasser. Band II,
Phenole. Boldt Verlag, Boppard, S. 101-115(59)

European inland fishery advisory commission, working party
on water quality criteria for European fresh water fish,
Water Res. 7, 929-941 (1973).

(60)

Portman JE and Wilson KW (1971) The toxicity of 140 substances
to the brown shrimp and other marine animals. Ministry ofagriculture, fisheries and food, Fisheries Lab. Shellfish
Inf. Leafl. no. 22: 1-11

(61)

Jones, H.R., Environmental control in the organic andpetrochemical industries. Noyes Data Corp. (1971).
Cited in: Verschueren, K., Handbook of environmental dataon organic chemicals. Van Nostrand Reinhold Co., New York,S. 406-408 (1983)

UNEP PUBLICATIONS

165

OECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(62)

Yoshioka Y, Mizuno, T, Ose, Y, Sato, T (1986) Chemosphere 15(2): 195-203(63)

Juhnke I and Luedemann D (1978) Z. Wasser Abwasser Forsch. 11: 161-164(64)

Vind, H.P. & Hochman, H., Toxicity of chemicals to marine
borers - 1. Interim report (technical report 048). US Naval
Civil Eng. Lab., Port Hueneme, 1-134 (1960)(65)

Bringmann G and Kuehn R (1982) Z. Wasser Abwasser Forsch. 15: 1-6(66)

Bringmann G and Kuehn R (1977) Z. Wasser Abwasser Forsch. 10: 161-166(67)

Devillers J (1987) Chemosphere 16: 1149-1163(68)

Devillers J (1988) Sci. Total Environ. 76: 79-83(69)

Parkhurst BR, Bradshaw AS, Forte JL, Wright GP (1979) Bull. Environ. Contam. Toxicol.
23: 349-356(70)

Bringmann G and Kuehn R (1959) Gesund.-Ing. 80: 115-120(71)

Verschueren, K., Handbook of environmental data on organic
chemicals. 2nd Ed., Van Nostrand Reinhold Co., New York, S.
406-408 (1983)(72)

Bringmann G and Kuehn R (1977) Z. Wasser Abwasser Forsch. 10: 87-98(73)

Huang JC and Gloyna EF (1968) effect of organic compounds on photosynthetic
oxygenation 1. Chlorophyll destruction and suppression of photosynthetic oxygen
production. Water Res 2: 347-366(74)

Bringmann G (1975) Gesund.-Ing. 96: 238-241(75)

Bringmann G and Kuehn R (1976) GWF-Wasser/Abwasser 117: 410-413(76)

Nobel W, Mayer T, Kohler A (1983) Z. Wasser Abwasser Forsch. 16(3): 87-90(77)

Pulich WM Jr, Winters K, Van Baalen C (1974) The effect of No. 2 fuel oil and two crude
oils on the growth and photosynthesis of microalgae. Mar. Biol. 28, 87-94(78)

Robinson JM, Allen BE, Denton TE (1976) Cresol induced growth inhibition in cultures ofchick fibroblasts and ankistrodesmus. J Alabama Acad Sci 47: 243-246(79)

Klecka GM and Landi LP (1985) Chemosphere 14 (9): 1239-1251(80)

Tomlinson TG, Boon AG, Trotman CNA (1966) J. Appl. Bact. 29 (2): 266-291(81)

Liu D (1985) Environ. Contam. Toxicol. 34: 331-339(82)

Blum DJW and Speece RE (1991) Research Journal WPCF 63 (3):198-207(83)

Warne MSJ, Connell DW, Hawker DW (1989) Chemosphere 19, 1113-1128(84)

Warne MSJ, Connell DW, Hawker, DW (1989) Wat. Sci. Tech. 21: 135-139(85)

Bringmann G, Kühn R, Winter A (1980) Z. Wasser Abwasser Forsch. 13: 170-173(86)

Bringmann G (1978) Z. Wasser Abwasser Forsch. 11: 210-215

166

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(87)

Schultz TW, Kyte LM, Dumont JN (1978) Arch. Environm. Contam. Toxicol. 7: 457-463(88)

Bringmann G and Kuehn R (1980) Z. Wasser Abwasser Forsch. 1: 26-31(89)

Bitton G (1983) Bacterial and Biochemical Tests for Assessing Chemical Toxicity in the
Aquatic Environment: A Review. Crit Rev Environ Control 13: 51 -67(90)

Hartung J (1987) Toxicity Assessment 2 (1): 1-15

(91)

Lebsack ME, Anderson AD, DeGraeve GM, Bergman HL (1981) Aquatic Toxicology andHazard Assessment: Fourth Conference, ASTM STP 737, D.R.Branson and K.L. Dickson,
Eds., American Society for Testing and Materials: 348-356(92)

Palmer LM, Baya AM, Grimes DJ, Colwell RR (1984) FEMS Microbiol. Lett. 21: 169-173(93)

Palmer LM, Baya AM, Xu HS, Grimes DJ (1983) Amer. Soc. Microbiol., Abstract Ann.
Meet., p. 276(94)

Cho, K.-Y. et al., Korean J. Appl. Microbiol. Bioeng. 17,
236-240 (1989)(95)

Kanne R, Rast HG, Springer W (1986) Analytik bakterientoxischer Effekte mit Hilfe
genetisch konstruierter Leuchtbakterien. Z Anal Chem 325 (1): 136 - 139(96)

Loveless LE, Spoerl E, Weisman TH (1954) J. Bacteriol. 68: 637-644(97)

Bringmann G and Kuehn R (1960) Ges.-Ing. 81 (11): 337-339(98)

Hulzebos EM, Adema DMM, Dirven-van Breemen, Henzen L, van Dis, WA, Herbold, HA,
Hoekstra JA, Baerselman, R, van Gestel CAM (1993) Environ. Toxicol. Chem. 12 (6):1079-1094(99)

Reynolds T (1978) Ann. Bot. 42, 419-427(100)

Yatagai M and Unrinin G (1989) Mokuzai Gakkaishi 35, 1021-1028(101)

Schafer EW Jr, Bowles WA Jr, Hurlbut J (1983) Arch. Environm. Contam. Toxicol. 12: 355382(102)

Layiwola PJ, Linnecar, DFC, Knights B (1983) Xenobiotica 13: 107-113(103)

Schroth MN and Hildebrand DC (1968) Phytopathol. 58, 848-854(104)

Leach FR, VanDoren SR, Frazier LB, Hall MS (1983) Development of a cell culture screen
for water toxicity (NTIS report no. PB83-220533). Oklahoma State Univ., Stillwater(105)

vanDoren SR, Hall MS, Frazier LB, Leach FR (1984) A rapid-cell culture assay of water
quality. Bull Environ Contam Toxicol 32: 220-226(106)

Gadaskina ID, Filov VA (1971) Transformations and determination of industrial poisons in
the human body. Leningrad, Meditsina, 202-205 cited in: IPCS (1993) Environmental
Health Criteria for cresols, first draft, IPCS/EHC/93.24. International Programme on
Chemical Safety(107)

Bray HG, Thorpe WV, White K (1950) Metabolism of derivatives of toluene. Biochem J 46:
275-278(108)

DeBruin A (1976) Metabolism of occupational agents. In: Biochem Toxicol Environm
Agents: Elsevier/North-Holland Biomedical Press, Amsterdam, p. 87-170

UNEP PUBLICATIONS

167

OECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(109)

Roberts MS, Anderson RA, Swarbrick J (1977) Permeability of human epidermis to thephenolic compounds. J Pharm Pharmac 29: 677-683(110)

Deichmann WB, Keplinger ML (1981) Phenols and phenolic compounds. In: Clayton GD
and Clayton FE (Eds.) Patty's industrial hygiene and toxicology. 3rd rev Ed Vol 2A, Wileyand Sons, New York, 2597-2601(111)

Wandel O (1907) Zur Pathologie der Lysol- und Kresolvergiftung. Arch Exp Pathol
Pharmacol 56: 161-186(112)

IPCS (International Programme on Chemical Safety) (1995) EHC (Environmental HealthCriteria) No. 168 Cresols. WHO, Geneva, pp. 144(113)

Mandel H.G. (1971) Pathways of Drug Biotransformation: Biochemical Conjugations in
LaDu B.N., Mandel H.G.adn Way E.L.(eds) Pathway of drug biotransformation: biochemical
conjugations Williams and Wilkins, Baltimore, pp: 149-186(114)

Scheline Ronald R. (1973) Metablism of foreign compounds by gastrointestinal
microorganisms, Pharmacological Reviews 25, 451-523(115)

Pereyman V (1977) Cytotoxicity of cresol isomers in aerosol in subtoxic concentrations.
Vrachebnoe Delo 5: 126-130(116)

BioFax Ind Bio-Test Lab Inc (1969) Data sheet no. 3-5/69(117)

Koch R, Nagel M, Schmidtke C, Schreckenbach M (1984) Die Stoffklassifizierung nachtoxikologischen Kriterien auf der Grundlage molekularer Strukturen. Zschr Ges Hyg 30:
199-203 (review)(118)

Deichmann WB, Witherup S (1944) Phenol studies VI: The acute and comparative toxicityof phenol and o-, m- and p-cresols for experimental animals. J Pharmacol Exp Therap 80:
233-240(119)

Uzhdavini ER et al (1974) Akute Toxizitaet niedriger Phenole. Gig Truda Prof Zabol 18: 5859 as cited in IPCS (1995)(120)

Mellon Inst Ind Res (1949) Special report on the acute toxicity of m-cresol. Univ. Pittsburgh,
USA, EPA/OTS 0517523(121)

Hazleton Lab. Am. Inc. (1989) HLA Study No. 100002-0-459 Acute Dose Selection Studyon meta-cresol. Rockville, USA, February 1, 1989 (at the request of CMA)EPA/OTS0529220(122)

Pereima V.L. 1975. Inhalational effect of cresol isomers at low concentrations and means
for improving detoxication processes in experiments on the white rats, Lvov, pp. 86-90,
cited in IPCS (1995), Environmental Health Criteria Report No 168, Cresols, International
Programme on Chemical Safety(123)

Vernot EH, MacEwen JD, Haun CC, Kinkead ER (1977) Acute toxicity and skin corrosion
data for some organic and inorganic compounds and aqueous solutions. Toxicol Appl
Pharmacol 42: 417-423(124)

Dittmer DS (Ed.) (1959) 64. m-cresol. Handbook of Toxicology, Vol V: 56-57(125)

Tollens K (1905) Ueber die Wirkung der Cresole und des Liquor Cresoli saponatus im
Vergleich zur Carbolsaeure. Arch Exp Pathol Pharmakol 52: 220-241(126)

Meili (1891); primary literature not available, cited in: Wandel O (1907) Zur Pathologie der
Lysol- und Kresolvergiftung. Arch Exp Pathol Pharmacol 56: 161-186

168

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(127)

Younger Laboratory (1974) Skin irritation in albino rabbits after application of o-, m- and pcresol, at the request if Productol Chemical Company, Whittler, California,
EPA/OTS0517499(128)

Kuroki K, Ohsumi T (1988) Locally injurious properties of the three isomeric cresols.
Kyushu Shika Gakkai Zasshi 42: 1037-1042(129)

Aerogen Inc. (2001) Inhalation safety of phenol and m-Cresol in rodents: a fourteen day
repeat dose toxicity study, study abstract as presented at ISAM Congress 2001

(130)

NTP (1991) Toxicity studies of cresols (CAS Nos 95-48-7, 108-39-4, 106-44-5) in F344/N
rats and B6C3F1 mice (feed studies), NTP-Tox 9. Research Triangle Park, NC, U.S.
Department of Health and Human Services, Public Health Service, National Institutes of
Health, National Toxicology Program(131)

Microbiological Associates Inc., Mulligan LT (1988) Subchronic toxicity of meta-cresol inSprague-Dawley rats, MBA Chemical No. 24, Study No. 5221.07, Final Report, Bethesda,
USA (at the request of Research Triangle Instiute: Dennis Dietz), NTIS Report No. PB88195284(132)

Shelley WB (1974) p-cresol: cause of ink-induced hair depigmentation in mice. Brit J
Dermatol 90: 169-174(133)

Jansson T, Curvall M, Hedin A, Enzell, CR (1986) In vitro studies of biological effects ofcigarette smoke condensate II. Induction of sister-chromatid exchanges in human
lymphocytes by weakly acidic, semivolatile constituents. Mutat Res 169: 129-139(134)

Nestmann ER Lee EG-H, Matula TI, Douglas GR, Mueller JC (1980) Mutagenicity of
constituents identified in pulp and paper mill effluents using the Salmonella/mammalianmicrosome assay. Mutat Res 79: 203-212(135)

Florin I, Rutberg, L, Curvall M, Enzell CR (1980) screening of tobacco smoke constituentsfor mutagenicity using the Ames' test. Toxicol 18: 219-232(136)

Hazleton Lab. Am. Inc. (1988) HLA Study No.10002-0-447 Mutagenicity test on metacresol in the rat primary hepatocyte unscheduled DNA synthesis assay. Kensington, USA,
June 28, 1988 (at the request of CMA)

(137)

Cheng M, Kligerman AD (1984) Evaluation of the genotoxicity of cresols using siterchromatid exchange (SCE). Mutat Res 137: 51-55(138)

Pool BL, Yalkinoglu AOe, Klein P, Schlehofer JR (1989) DNA amplification in genetic
toxicology. Mutat Res 213: 61-72(139)

Moore SP, Coohill TP (1983) An SV40 mmmalian inductest for putative carcinogens. Prog
Nucl Acids Res Mol Biol 29: 149-153(140)

Hejtmankova N, Simanek V, Holcik J, Hejtmanek M, Santavy F (1979) antifungal andmutagenic activity of phenolic substances with different alkyl groups II. A study of therelationship between the biological activity and the constitution of the investigatedcompounds. Acta Univ Olomucensis Fac Med 90: 75-87(141)

Ohshima H, Friesen M, Malaveille C, Brouet I, Hautefeuille A, Bartsch H (1989) Formationof direct-acting genotoxic substances in nitrosated smoked fish and meat products:
identification of simple phenolic precursors and phenyldiazonium ions as reactive products.
Fd Chem Toxicol 27: 193-203(142)

Elespuru RK, Pennington RW (1981) Alternate pathways of induction of bacteriophage
lambda by diverse chemicals. Environm Mutagen 3: 387

UNEP PUBLICATIONS

169

OECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(143)

Levan A, Tjio JH (1948) Induction of chromosome fragmentation by phenols. Hereditas 34:
453-484(144)

Hazleton Lab. Am. Inc. (1988) HLA Study No. 10002-0-431 Mutagenicity test on metacresol in a mouse lymphoma mutation assay, Kensington, USA (at the request of CMA)EPA/OTS0517693(145)

Sharma AK, Ghosh S (1965) Chemical basis of the action of cresols and nitrophenols on
chromosomes. The Nucleus 8: 183-190(146)

Pool BL, Lin PZ (1982) Mutagenicity testing in the Salmonella typhimurium assay ofphenolic compounds and phenolic fractions obtained from smokehouse smoke
condensates. Fd Chem Toxic 20: 383-391(147)

Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E (1983) Salmonella mutagenicity
test results for 250 chemicals. Environm Mutagen 5, Suppl. 1: 3-142(148)

Hazleton Lab. Am. Inc. (1988) HLA Study No. 10002-0-437 Mutagenicity test on m-cresol
in an in-vitro cytogenetic assay measuring chromosomal aberration frequencies in Chinese
Hamster Ovary (CHO) cells. Kensington, USA, June 28, 1988 (at the request of CMA)EPA/OTS0517691(149)

Hamaguchi F, Tsutsui T (2000) Assessment of genotoxicity of dental antiseptics: ability ofphenol, guaiacol, p-phenolsulfonic acid, sodium hypochlorite, p-chlorophenol, m-cresol orformaldehyde to induce unscheduled DNA syntehsis in cultured Syrian Hamster embryo
cells. Jpn J Pharmacol 83: 273-276(150)

Hazleton Lab. Am. Inc. (1989) HLA Study No. 10002-0-451 Mutagenicity test on metacresol in a mouse bone marrow cytogenetic assay. Kensington, USA, January 31, 1989 (atthe request of CMA)

(151)

Boutwell RK, Bosch DK (1959) The tumor-promoting action of phenol and related
compounds for mouse skin. Cancer Res 19: 413-424(152)

Hazleton Lab. Am. Inc. (1988) HLA Study No. 10002-0-441 Genetic toxicology test on
meta-cresol in the in vitro transformation of Balb/c-3T3 cells assay. Kensington, USA, June
1988 (at the request of CMA) EPA/OTS 517694; EPA/OTS0517698(153)

Hazleton Lab. Am. Inc. (1988) HLA Stud. No. 10002-0-488A Mutagenicity test on metacresol in the in vitro transformation of Balb/c-3T3 cells assay in the presence of a rat liver
cell activation system. Kensington, USA (at the request of CMA)

(154)

Tsutsui T, Suzuki N, Kobayashi Y, Suzuki H, Fukuda S, Maizumi H (1987) Assessment of
the carcinogenic hazard of 27 substances used in dental practices. Jpn J Pharmacol 43:
132P

(155)

Bushy Run Research Centre (1989) Project-Report No. 51-634, Two-Generation
Reproduction Study of m-Cresol administered by gavage to Sprague-Dawley (CD) rats,
November/1989 (at the request of CMA)

(156)

Bushy Run Research Center/Hazleton Laoratories (1988a) Project report 51-509
Developmental toxicity evaluation of o-, m-, or p-cresol administered by gavage toSprague-Dawley (CD) rats, June,1988 (at the request of CMA)

(157)

Bushy Run Research Center (BRRC Project No. 87-81-96103) (1987) Developmental
toxicity dose-range finding study of o-, m-, or p-cresol administered by gavage to New
Zealand white rabbits, 1987, USA (at the request of CMA)

170

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(158)

Bushy Run Research Centre/Hazleton Laboratories (1988b) Project Report 51-508,
Developmental toxicity evaluation of o-, m-, or p-cresol administered by gavage to New
Zealand White rabbits, June, 1988 (at the request of CMA), EPA/OTS0517695(159)

Akatsuka K, Hashimoto T, Takeuchi K, Hara M, Maeda H, Matsui M, Shimizi Y (1978)
Reproduction studies swine prostate extract of (Robaveron R) (3) Teratogenic study in rats.
Oyo Yakuri 16: 1169-1179(160)

Akatsuka K, Hashimoto T, Takeuchi K, Hara M, Maeda H, Matsui M, Shimizi Y (1978)
Reproduction studies swine prostate extract of (Robaveron R) (4) Prenatal and postnatal
study in rats. Oyo Yakuri 16: 1181-1190(161)

Akatsuka K, Hashimoto T, Takeuchi K, Hara M, Odaka M, Maeda H, Matsui M, Shimizi Y(1977) Reproduction studies swine prostate extract of (Robaveron R) (1) The effect ofRobaveron administered to pregnant mouse on pre- and post-natal development of theiroffsprings. Oyo Yakuri 14: 369-378(162)

Akatsuka K, Hashimoto T, Takeuchi K, Hara M, Maeda H, Matsui M, Shimizi Y (1978)
Reproduction studies swine prostate extract of (Robaveron R) (5) Teratogenic study in
rabbits. Oyo Yakuri 16: 1191-1199(163)

ATSDR (1990) Draft toxicological profile for cresols: o-cresol, p-cresol, m-cresol. Agency
for Toxic Substances and Disease Registry, US Public Health Service(164)

TRL (1986) Summary of subchronic neurotoxicity study in rats of ortho-, meta-, and paracresol. Unpublished data submitted by Toxicity Research Laboratories to EPA(165)

Angerer J (1979) Occupational chronic exposure to organic solvents VII. Metabolism ofToluene in man. Int Arch Occup Health 43: 63-67(166)

Bieniek G, Wilczok T (1986) Separation and determination of phenol, alpha-naphthol, mand p-, o-cresols and 2,5-xylenol, and catechol in the urine after mixed exposure to phenol,
naphthalene, cresols, and xylenols. Brit J Ind Med 43: 570-571(167)

Kawai T (1986) Measurement of urine metabolites after exposure to benzene, toluene andphenols, and application to biological monitoring. Osaka City Med Cent J 34: 249-266(168)

Kira S, Ogata M, Horii S, Ebara Y, Otsuki S, Kawai T, Yasugi T (1989) A case of thinnner
sniffing: Part 2. Urinary excretion of cresols and methanol after inhalation of toluene andmethanol. Industrial Health 27: 175-180(169)

Kono K, Yoshida Y, Yamagata H, Watanabe M, Takeda Y, Murao M, Doi K, Takatsu M(1985) Urinary excretion of cresol as an indicator for occupational toluene exposure.
Industrial Health 23: 37-45(170)

Meulenbelt J, DeGroot G, Savelkoul TJF (1990) Two cases of acute toluene intoxication.
Brit J Ind Med 47: 417-420(171)

Woiwode W, Drysch K (1981) Experimental exposure to toluene: further consideration ofcresol formation in man. Brit J Ind Med 38: 194-197(172)

Gleason MN, Gosselin RE, Hodge HC, Smith RP (1969) Clinical toxicology of commercial
products. Acute poisoning. third ed., The Williams & Wilkins Co., Baltimore, p. 42(173)

van Faassen I, Verweij-van Vught AMJJ, Lomecky-Janousek MZ, Razenberg PPA, van derVeen EA (1990) Preservatives in insulin preparations impair leukocyte function. Diabetes
Care 13: 71-74(174)

Wu ML, Tsai WJ, Yang CC, Deng JF (1998) Concentrated cresol intoxication. Vet Human
Toxicol 40: 341-343

UNEP PUBLICATIONS

171

OECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(175)

Evers J, Aboudan F, Lewalter J, Renner E (1994) Hemodialysis in metacresol poisoning.
Clin Investig 72: 472(176)

Chou C-HSJ, Holler J, DeRosa CT (1998) Minimal risk levels (MRLs) for hazardous
substances. J Clean Technol Environ Toxicol Occup Med 7: 1-24

(177)

Bruce AM, Smith H, Watson AA (1976)Cresol poisoning. Med Sci Law 16: 171-176(178)

Cote MA, Lyonnais J, Lblond PF (1984) Acute Heinz body amnemia due to severe cresol
poisoning: successful treatment with erythrocytapheresis. Can. Med. Assoc J 130: 13191322(179)

DECOS (Dutch Expert Commitee on Occupational Standards)(1998) Cresols(o-, m-,p).
Health-based recommended occupational exposure limits 1998/27, health council of theNetherlands, Den Haag

(180)

Minami M. Katsumata M, Tomoda A (1990) Methemoglobinemia with oxidized hemoglobins
and modified hemoglobins found in bloods of workers handling aromatic compounds and in
those of a man who drank cresol solution. Biomed Biochim Acta 49: 327-333(181)

Lin CH and Yang JY (1992) Chemical burn with cresol intoxication and multiple organ
failure. Burns 18: 162-166(182)

Garrett JS: Association between bladder tumours and chronic exposure to cresol andcreosote. J. Occup. med 17, 492(183)

Richardson D, Dorris TC, Burks S, Browne RH, Higgins ML, Leach FR (1977) Evaluation ofa cell culture assay for determination of water quality of oil-refinery effluents. Bull Environ
Contam Toxicol 18: 683-690(184)

Takagi H (1987) Effect of m-cresol on cultured V79 cells. Shigaku 75: 37-49(185)

Baldwin BC, Robinson D, Williams RT (1959) Studies in Detoxication 78. Glucuronide andethereal sulphate formations in hens. Biochem J 71: 638-642(186)

Ungvary G, Janos K, Szabolcs S (1988) Alteration of metabolism of xylene in rats
pretreated with silymarine + silybinine (Legalon(R) 70). Egeszsegtudomany 32: 74-78(187)

Preusse C (1881) Zur Kenntnis der Oxydation aromatischer Substanzen im Thierkoerper.
Hoppe-Seylers Zschr fuer Physiol Chemie 5: 57-66(188)

Sato T, Suzuki T, Fukuyama T (1956) Studies on conjugation of s35-sulfate with phenolic
compounds IV. Metabolism of o-cresol, m-cresol, salicylaldehyde, salicylic acid, toluene,
benzoic acid and related substances in rat liver. J Biochem 43: 421-429(189)

Chen T-H, Kavanagh TJ, Chang CC, Trosko JE (1984) Inhibition of metabolic cooperationin Chinese Hamster V79 cells by various organic solvents and simple compounds. Cell Biol
Toxicol 1: 155-171(190)

Lunde PKM, Waaler BA, Walloe L (1968) The inhibitory effect of various phenols upon
ATP-induced vasoconstriction in isolated perfused rabbit lungs. Acta Physiol Scand 72:
331-337(191)

Dalhamn T (1968) Ciliostatic effect of orthocresol and metacresol. Arch Otolaryng 87: 162164(192)

Babich H, Borenfreund E (1987) Structure-activity relationship (SAR) models established invitro with the neutral red cytotoxicity assay. Toxic in Vitro 1: 3-9

172

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m-CRESOL
ID: 108-39-4
DATE: 24.05.2004(193)

Hohenegger M, Echsel H, Vermes M, Raneburger H (1987) Influence of some uremic
toxins on oxygen consumption of rats in vivo and in vitro. Adv Exp Med Biol 212: 99-104(194)

Hohenegger M, Vermes M, Esposito R, Giordano C (1988) Effect of some uremic toxins on
oxygen consumption of rats in vivo and in vitro. Nephron 48: 154-158(195)

Curvall M, Enzell CR, Pettersson B (1984) An evaluation of the utility of four in vitro shortterm tests for predicting the cytotoxicity of individual compounds derived from tobaccosmoke. Cell Biol Toxicol 1: 173-193(196)

Cheng SC, Pardini RS (1979) Inhibition of mitochondrial respiration by model phenolic
compounds. Biochem Pharmacol 28: 1661-1667(197)

Kushi A, Yoshida D (1987) Antimutagenic effects of phenols on MNNG-induced
mutagenesis in Escherichia coli. Agric Biol Chem 51: 1439-1440(198)

Anamura S (1989) Effects of phenolic dental medications on arachidonic acid metabolism
and their inflammation inhibitors and immune agents. Hiroshima Daigaku Shigaku Zasshi
21: 147-162(in Japanese, engl. Abstract)

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p-CRESOLIUCLID
Data Set
Existing Chemical
CAS No.
EINECS NameEC No.
TSCA Name
Molecular Formula

:
:
:
:
:
:

ID: 106-44-5
106-44-5
p-cresol
203-398-6
Phenol, 4-methylC7H8O

Producer related part
Company
Creation date

: Bayer AG: 11.01.2001

Substance related part
Company
Creation date

: Bayer AG: 11.01.2001

StatusMemo:: AKTUELL / ICCA (Category Cresols)

Printing date
Revision date
Date of last update: 24.05.2004:: 24.05.2004

Number of pages: 122

Chapter (profile)
Reliability (profile)
Flags (profile): Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10: Reliability: without reliability, 1, 2, 3, 4
: Flags: without flag, non confidential, WGK (DE), TA-Luft (DE), Material
Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDS

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1. GENERAL INFORMATION

1.0.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

APPLICANT AND COMPANY INFORMATION

Type
Name
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Date
StreetTown
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Cedex
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Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
ADCHEMCO Corporation

Flag
31.05.2001:

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:
:
:
:
:
:
:
:
:
:
:
:
:

lead organisation
American Chenistry Council Cresol Panel

Flag
16.01.2001:

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:
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:
:
:
:
:
:
:
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:

cooperating company
Bayer Corporation

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16.01.2001:

Critical study for SIDS endpoint

Type
Name
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Date
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:
:
:
:
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:

cooperating company
Concord Chemical Company

Japan

1300 Wilson Blvd.
22209 Arlington, VA
United States703-741-5629

United States

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1. GENERAL INFORMATION

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:

United StatesFlag
16.01.2001:

Critical study for SIDS endpoint

Type
Name
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Date
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:
:
:
:
:
:
:
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:

cooperating company
Dakota Gasification Company

Flag
16.01.2001:

Critical study for SIDS endpoint

Type
Name
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Date
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:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Honshu Chemical Industry Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
LaPorte (formerly Inspec Fine Chemicals, Inc.)

Flag
17.01.2001:

Critical study for SIDS endpoint

176

United States

Japan

United States

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Merisol (Merichem-Sasol USA LLC)

Flag
17.01.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Mitsui Chemicals, Inc.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Nippon Steel Chemical Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax

:
:
:
:
:
:
:
:
:

cooperating company
PMC Specialties Group, Inc.

United States

Japan

Japan

United States

UNEP PUBLICATIONS

177OECD SIDS
1. GENERAL INFORMATION

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Telex
Cedex
Email
Homepage

:
:
:
:

Flag
16.01.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumiken Chemical Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumitomo Chemical Americas, Inc.

Flag
16.01.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumitomo Chemical Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

178

Japan

United States

Japan

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

1.0.2

LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR

1.0.3

IDENTITY OF RECIPIENTS

1.0.4

DETAILS ON CATEGORY/TEMPLATE

1.1.0

SUBSTANCE IDENTIFICATION

1.1.1

GENERAL SUBSTANCE INFORMATION

Purity type
Substance typePhysical status
PurityColour
Odour

:
:
:
:
:
:

Flag
10.02.2003:

organic
solid
ca. 99.9 % w/w

Critical study for SIDS endpoint
(1)

1.1.2

SPECTRA

1.2

SYNONYMS AND TRADENAMES

1-Hydroxy-4-methylbenzene
01.05.1998
4-Cresol
01.05.1998
4-Hydroxytoluene
01.05.1998
4-Hydroxytoluol, 4-Methylphenol
19.05.1998
4-Methylfenol
06.03.1998
4-Methylphenol
01.05.1998
p-Cresol (8CI)
30.08.1996

UNEP PUBLICATIONS179OECD SIDS
1. GENERAL INFORMATION

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

p-Cresylic acid
01.05.1998
p-Hydroxytoluene
01.05.1998
p-Kresol
01.05.1998
p-Methylhydroxybenzene
23.05.2002
p-Methylphenol
01.05.1998
p-Oxytoluene
01.05.1998
p-Toluol
01.05.1998
p-Tolyl alcohol
23.05.2002
paracresol
01.05.1998
Phenol, 4-methyl01.05.1998
Phenol, 4-methyl- (9CI)
30.08.1996
1.3

IMPURITIES

1.4

ADDITIVES

1.5

TOTAL QUANTITY

Quantity:- tonnes produced in

Remark
Flag
28.05.2002::

59,500 tonnes in 2000, estimated world capacity
Critical study for SIDS endpoint

180

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION
1.6.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

LABELLING

LabellingSpecific limits
Symbols
Nota
R-Phrases

:
:
:
:
:

S-Phrases:

Remark
Flag
24.05.2002::

19. Adaptation, EC-Index-No. 604-004-00-9
Critical study for SIDS endpoint

Classified
Class of danger
R-Phrases
Specific limits

:
:
:
:

as in Directive 67/548/EEC
corrosive(34) Causes burns

Flag
24.05.2002:

Critical study for SIDS endpoint

Classified
Class of danger
R-Phrases
Specific limits

:
:
:
:

as in Directive 67/548/EEC
toxic(24/25) Toxic in contact with skin and if swallowedFlag
24.05.2002:

Critical study for SIDS endpoint

Type of use
Category::type
Use in closed systemFlag
24.05.2002:

Critical study for SIDS endpoint

Type of use
Category::

industrial
Chemical industry: used in synthesis

Flag
24.05.2002:

Critical study for SIDS endpoint

Type of use
Category::useIntermediates

1.6.2

as in Directive 67/548/EEC
T, , ,,,(24/25) Toxic in contact with skin and if swallowed(34) Causes burns(36/37/39) Wear suitable protective clothing, gloves and eye/faceprotection(45) In case of accident or if you feel unwell, seek medical advice
immediately (show the label where possible)

CLASSIFICATION

1.6.3

PACKAGING

1.7

USE PATTERNUNEP PUBLICATIONS

181

OECD SIDS
1. GENERAL INFORMATION
Flag
24.05.2002:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Critical study for SIDS endpoint

1.7.1

DETAILED USE PATTERN

1.7.2

METHODS OF MANUFACTURE

1.8

REGULATORY MEASURES

1.8.1

OCCUPATIONAL EXPOSURE LIMIT VALUES

Type of limit
Limit value::

MAC (NL)
22 mg/m3

Remark
22.03.2001:

Skin (all isomers).

Type of limit: MAK (DE)
Limit value: 22 mg/m3
Short term exposure limit value
Limit value: 22 mg/m3
Time schedule:
Frequency: times
RemarkSourceFlag
24.05.2002:::

all isomers danger of cutaneous absorption
TRGS 900 (DE)
Critical study for SIDS endpoint

Type of limit
Limit value::

MAK (DE)

Remark:danger of cutaneous absorption
Mak list, canc. category 3A

27.05.2002(2)

Type of limit: MAK (DE)
Limit value: 5 ml/m3
Short term exposure limit value
Limit value: 5 ml/m3
Time schedule:
Frequency: times
RemarkSourceFlag
24.05.2002:::

danger of cutaneous absorption
TRGS 900 (DE)
Critical study for SIDS endpoint

Type of limit
Limit value::

OES (UK)
22 mg/m3

RemarkSource::Skin (all isomers).
Synthetic Chemicals Ltd. Wolverhampton
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

16.05.1994

182

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Type of limit
Limit value::

TLV (US)
5 other: ppm

Remark

:Flag
22.03.2001:

Skin notation. Critical effects: dermatitis, irritation,
CNS.
Critical study for SIDS endpoint

Type of limit
Limit value::

TLV (US)22 mg/m3

Remark

:Flag
22.03.2001:

Skin notation. Critical effects: dermatitis, irritation,
CNS.
Critical study for SIDS endpoint

1.8.2

ACCEPTABLE RESIDUES LEVELS

1.8.3

WATER POLLUTIONClassified byLabelled byClass of danger:::

KBwS (DE)KBwS (DE)
2 (water polluting)

24.05.2002
1.8.4

MAJOR ACCIDENT HAZARDS

Legislation
Substance listed
No. in Seveso directive:::

Stoerfallverordnung (DE)yesAppendix I, No. 2

:
:
:
:

TA-Luft (DE)24.05.2002
1.8.5

AIR POLLUTIONClassified byLabelled byNumberClass of danger

3.1.7 (organic substances)I

24.05.2002
1.8.6

LISTINGS E.G. CHEMICAL INVENTORIES

1.9.1

DEGRADATION/TRANSFORMATION PRODUCTS

1.9.2

COMPONENTS

UNEP PUBLICATIONS

183

OECD SIDS
1. GENERAL INFORMATION
1.10

SOURCE OF EXPOSURE

1.11

ADDITIONAL REMARKS

Remark:Source:p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Opmerkingen: Transportclassificering volgens RID/ADR: kl
6.1-27b / UN no. 2076
B.V. CONSOLCO Amsterdam
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

06.03.1998
1.12

LAST LITERATURE SEARCH

Type of search
Chapters covered
Date of search:::Internal and External

Remark

:Toxicology: November 2002
Environmental aspects and ecotoxicology: January 2002
CAS number search in external and internal databases, e.g. HSDB, Aquire,
Biosis, Embase, Toxline, Scisearch.

22.01.2003
1.13

184

REVIEWS

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA

2.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

MELTING POINT

Value
Sublimation
MethodYear
GLP
Test substance

:
:
:
:
:
:

34.7 °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Sublimation
MethodYear
GLP
Test substance

(3)
:
:
:
:
:
:

34.8 °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Sublimation
MethodYear
GLP
Test substance(4) (5)
:
:
:
:
:
:

35.3 °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004

(6)

Value
Sublimation
MethodYear
GLP
Test substance

:
:
:
:
:
:

Remark
Flag
11.05.2004

:
:

Value
Sublimation
MethodYear
GLP
Test substance

:
:
:
:
:
:

35.5 °C
other: no data available
no dataother TS: p-cresol, no purity reported
SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint(7) (8)ca. 34 °C
other: no data available
no dataother TS: p-cresol, no purity reported, but < 0.9 % of m-cresol

11.05.2004
2.2

(9)

BOILING POINT

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

201.9 °C at 1013 hPaother: no data available
no dataother TS: p-cresol, no purity reported

UNEP PUBLICATIONS

185

OECD SIDS
2. PHYSICO-CHEMICAL DATA

Remark
Flag
11.05.2004

:
:

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint(7)
201.9 °C atother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(3)
:
:
:
:
:
:

202 °C atother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance(6) (4)
:
:
:
:
:
:

ca. 202 °C atother: no data available
no dataother TS: p-cresol, no purity reported, but < 0.9 % of m-cresol

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(9)
:
:
:
:
:
:

201.8 °C at 1013 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

179.4 °C at 267 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

140 °C at 133 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition

186

(8)
:
:

117.7 °C at 53.3 hPa

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
MethodYear
GLP
Test substance

:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

102.3 °C at 26.7 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

88.6 °C at 13.3 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

76.5 °C at 6.58 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

53 °C at 1.32 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

85.7 °C at 13.3 hPaother: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
2.3

(5)

DENSITY

Type
Value
MethodYear
GLP
Test substance

:
:
:
:
:
:

1.0178 g/cm³ at 20 °C
other: no data available
no dataother TS: p-cresol, no purity reported

UNEP PUBLICATIONS

187

OECD SIDS
2. PHYSICO-CHEMICAL DATA

Flag
11.05.2004

:

Type
Value
MethodYear
GLP
Test substance

:
:
:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Critical study for SIDS endpoint(5)
1.0341 g/cm³ at 20 °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Type
Value
MethodYear
GLP
Test substance(3) (8)
:
:
:
:
:
:

1.04 g/cm³ at 20 °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Type
Value
MethodYear
GLP
Test substance

(4)
:
:
:
:
:
:

1.0185 g/cm³ at 40 °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Type
Value
MethodYear
GLP
Test substance

(10)
:
:
:
:
:
:

1.039 g/cm³ at °C
other: no data available
no dataother TS: p-cresol, no purity reported

11.05.2004
Type
Value
MethodYear
GLP
Test substance

(6)
:
:
:
:
:
:

ca. 1.034 g/cm³ at 20 °C
other: no data available
no dataother TS: p-cresol, no purity reported, but < 0.9 % of m-cresol

11.05.2004

(9)

2.3.1

GRANULOMETRY

2.4

VAPOUR PRESSURE

Value
Decomposition
Method
Year
GLP

188

:
:
:
:
:

.053 hPa at 20 °C

no data

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
Test substance:p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

other TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(4)
:
:
:
:
:
:

.1 hPa at 20 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(3)
:
:
:
:
:
:

ca. .1 hPa at 20 °C

no dataother TS: p-cresol, no purity reported, but < 0.9 % of m-cresol

11.05.2004

(9)

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

.147 hPa at 25 °C
other (measured)
1989
no dataother TS: p-cresol, no purity reported

Remark
Flag
11.05.2004::

SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

(11)
.15 hPa at 25 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(4)
:
:
:
:
:
:

.24 hPa at 30 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(3)
:
:
:
:
:
:

1.1 hPa at 50 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value

(3)
:

ca. 1.1 hPa at 50 °C

UNEP PUBLICATIONS

189

OECD SIDS
2. PHYSICO-CHEMICAL DATA
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

no dataother TS: p-cresol, no purity reported, but < 0.9 % of m-cresol

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(9)
:
:
:
:
:
:

1.3 hPa at 53 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(4)
:
:
:
:
:
:

6.58 hPa at 76.5 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

13.3 hPa at 85.7 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(5)
:
:
:
:
:
:

13.3 hPa at 88.6 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

26.7 hPa at 102.3 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

53.3 hPa at 117.7 °C

no dataother TS: p-cresol, no purity reported

11.05.2004

190

(8)

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

133 hPa at 140 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

267 hPa at 179.4 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Value
Decomposition
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:

ca. 1013 hPa at 202 °C

no dataother TS: p-cresol, no purity reported

11.05.2004
2.5

(8)

PARTITION COEFFICIENT

Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

other (measured)

Remark
Flag
11.05.2004::

experimental data, SRC (EPI Suite v 3.10) recommended value
Critical study for SIDS endpoint

Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

octanol-water
1.94 at °C

no dataother TS: p-cresol, no purity reported(12)octanol-water= 1.94 at °C

no dataother TS: p-cresol, no purity reported

11.05.2004
Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

(4)
:
:
:
:
:
:
:

octanol-water
1.92 at °C

no dataother TS: p-cresol, no purity reported

UNEP PUBLICATIONS

191

OECD SIDS
2. PHYSICO-CHEMICAL DATA

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

11.05.2004(4)

Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

octanol-water
1.92 - 1.99 at °C

Remark11.05.2004:

4 log Kow values in the range of 1.92 to 1.99 cited

2.6.1

no dataother TS: p-cresol, no purity reported(13)

SOLUBILITY IN DIFFERENT MEDIA

Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Water
21.5 g/l at 25 °C

Remark
Flag
11.05.2004::

SRC recommended value
Critical study for SIDS endpoint

Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

at °C
at 25 °C

other: measured
1992
no dataother TS: p-cresol, no purity reported

(14)
Water
= 19.5 g/l at 20 °C
at °C
at 25 °C

other: measured
1991
no dataother TS: p-cresol, purity not noted

11.05.2004
Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
Stable

192

(15)
:
:
:
:
:
:
:
:
:

Water
ca. 21 g/l at 25 °C
at °C
at 25 °C

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

other: no data available
no dataother TS: p-cresol, no purity reported, but < 0.9 % of m-cresol

11.05.2004
Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

(9)
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Water
24 g/l at 40 °C
at °C
at 25 °C

other: no data available
no dataother TS: p-cresol, purity not noted

11.05.2004
Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

(4)
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Water
25 g/l at 50 °C
at °C
at 25 °C

other: no data available
no dataother TS: p-cresol, purity not noted

11.05.2004
Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

(8)
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Water
50 g/l at 100 °C
at °C
at 25 °C

other: no data available
no dataother TS: p-cresol, purity not noted

11.05.2004
Solubility in
Value

(8)
:
:

Water
53 g/l at 100 °C

UNEP PUBLICATIONS

193

OECD SIDS
2. PHYSICO-CHEMICAL DATA
pH

value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

at °C
at 25 °C

other: no data available
no dataother TS: p-cresol, purity not noted

11.05.2004
2.6.2

SURFACE TENSION

2.7

FLASH POINT

Value
Type
MethodYear
GLP
Test substance

(4)

:
:
:
:
:
:

86 °C
closed cup
other: DIN 51758
no dataother TS: p-cresol, no purity reported, but according to Bayer MSDS < 0.9% of m-cresol

11.05.2004
2.8(9) (8) (6)

AUTO FLAMMABILITY

Value
MethodYear
GLP
Test substance

:
:
:
:
:

558 °C atother: DIN 51794

Remark11.05.2004:

autoignition temperature

2.9

no dataother TS: p-cresol, no purity reported, but according to Bayer MSDS < 0.9% of m-cresol(9) (6)

FLAMMABILITY

22.03.2001
2.10

EXPLOSIVE PROPERTIES

22.03.2001

194

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
2.11

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

OXIDIZING PROPERTIES

22.03.2001
2.12

DISSOCIATION CONSTANT

Acid-base constantMethodYear
GLP
Test substance

:
:
:
:
:

10.2
other: no data available
1987
no dataother TS: p-cresol, no purity reported

Remark11.05.2004:

secondary citation

Acid-base constantMethodYear
GLP
Test substance

:
:
:
:
:

10.26
other: measured and calculated
1968
noother TS: p-cresol, no purity reported

Method:RemarkResultFlag
11.05.2004:::

Experimental data for cresols were taken from Kortuem G, Vogel W, andAndrussow K (1961) Dissociation Constants of Organic Acids in Aqueous
Solution. Butterworths, Lon-don
For experimental data: Secondary literature
Calculated result is pk = 10.32
Critical study for SIDS endpoint(17)

Acid-base constantMethodYear
GLP
Test substance

:
:
:
:
:

10.70
other: measured
1971
noother TS: m-cresol, no purity reported, but substance purified by distillation
under reduced pressure

Method:Remark11.05.2004:

Measured according to Bordwell FG and BD Cooper (1952) J. Am. Chem.
Soc. 74, 1058
in 20 % water-ethanol (v/v) at 20 °C
(18)

(16)

2.13

VISCOSITY

2.14

ADDITIONAL REMARKS

Memo

:

Refraction index

Remark11.05.2004:

Refraction index (nD): 1.5312 at 20 degrees C

Memo

:

Refraction index

Remark11.05.2004:

Refraction index (nD): 1.5395 at 20 degrees C

(10)

(8)

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2. PHYSICO-CHEMICAL DATA

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Memo

:

Odor

Remark:Treshold odor concentration in water: 0.200 ppm
Treshold taste concentration in water: 0.002 ppm

11.05.2004

196

(19)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

3.1.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

PHOTODEGRADATION

Type:Light source:
Light spectrum:
Relative intensity:
INDIRECT PHOTOLYSIS
Sensitizer:
Conc. of sensitizer:
Rate constant:Degradation:
Deg. product:
Method
:
Year
:
GLP
:
Test substance:
Remark:Reliability:

Flag
10.05.2004:

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition:

Reliability:

Flag
12.05.2004:

Type
Light source
Light spectrum
Relative intensity
Deg. product
Method
Year

:
:
:
:
:
:
:

air
nm
based on intensity of sunlightOH
500000 molecule/cm³.0000000000873 cm³/(molecule*sec)
50 % after 8.2 hour(s)other (calculated): with SRC-AOPWIN, v1.90
2003

The calculated half-life is based on a mean OH radical concentration of
0.5E+6 OH radicals/cm3 given during the 24 hours/day as suggested in the
EU-Technical Guidance Document(2) valid with restrictions
Generally accepted calculation method
Critical study for SIDS endpoint
(20)
air
nm
based on intensity of sunlightother (measured)
1995
no dataother TS: p-cresol, purity > 99 %Determination of the temperature-dependency of the OH
radical reaction under simulated tropospheric conditions
With a OH radical concentration of 1 000 000 molec cm-3 anda temperature of 301 K, the half-life is 3.8 h
kOH = 2.21 x 10E-12 exp[(943+-449)/T] cm3 molec.-1 s-1 for atemperature range of 301-373 K
test substance concentration 0.05-5 ppm
reference compound (1,3-butadiene or o-cresol) 0.05-2.3 ppm
radical source methylnitrite 1.5-11 ppm together with NOx
2-70 ppm(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions
Critical study for SIDS endpoint
(21)
air
nm
based on intensity of sunlightother (measured): critical review
1994

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
GLP
Test substance::

Remark:Result:Reliability:

Flag
07.05.2004:

Type
Light source
Light spectrum
Relative intensity
Conc. of substanceDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

Flag
10.05.2004:

other TS: p-cresol, no purity reported
With a OH radical concentration of 1 000 000 molec/cm3, thehalf-life is 4.1 h
K[OH] = 4.7 [10E-11 cm3 molecule-1 s-1]
K[NO3] = 1.07 [10E-11 cm3 molecule-1 s-1]
K[O3] = 4.7 [10E-19 cm3 molecule-1 s-1]
(1) valid without restriction
Critical review, evaluation of all available experimental
data
Critical study for SIDS endpoint(22) (23) (24)Type:Light source:
Light spectrum:
Relative intensity:
INDIRECT PHOTOLYSIS
Sensitizer:
Conc. of sensitizer:
Rate constant:Degradation:
Deg. product:
Method
:
Year
:
GLP
:
Test substance:198

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

water
nm
based on intensity of sunlightat 19 °C1987
no dataother TS: p-cresol, no purity reported, but of highest commercial purity
available
Determination of rate constant for reaction with singlet
oxigenINDIRECT PHOTOLYSIS:- Rate constant: 1.1 E7 M-1 s-1 at pH 8.3
2.4 E7 M-1 s-1 at pH 8.8
1.6 E8 M-1 s-1 at pH 10
3.5 E8 M-1 s-1 at pH 11.5
- Half life t1/2: 500 h under noon summer sunlight(Switzerland) with 4E-14 M singlet oxygen- Test medium: aqueous solution containing 0.05M phosphatebuffer and 5 mg/l rose bengal- Test system: merry-go-round reactor- Concentration of test substance: < 0.0001 M
Duration: < 2 hours(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint
(16)
air
nm
based on intensity of sunlightOH
cm³/(molecule*sec)% afterother (measured)
1990
no dataother TS: p-cresol, purity > 99 % (obtained from Aldrich Chemical
Company)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

MethodResult
Test condition:::

Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

smog chamber experiment with black light irradiation
k[OH] = 4.84 +- 0.89 [10E-11 cm3 molecule-1 s-1]
dry air pressure 735 Torr
Temp. 296 +- 2 K
irradiation time 4-20 min
reference substance: propene
OH radical concentration: (1-3) x 10E7 molecule/cm-3(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

10.05.2004

(25)

Type
:
Light source:
Light spectrum:
Relative intensity:
INDIRECT PHOTOLYSIS
Sensitizer:
Conc. of sensitizer:
Rate constant:Degradation:
Deg. product:
Method
:
Year
:
GLP
:
Test substance:
Method:Result:Reliability

:

air
nm
based on intensity of sunlightOH
cm³/(molecule*sec)% after1987
no dataother TS: p-cresol, no purity reported
I. Smog chamber experimentII. Inkrement methodk[OH] = 44 [10E-12 cm3 molecule-1 s-1] both observed andcalculated(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

10.05.2004

(26)

Type
:
Light source:
Light spectrum:
Relative intensity:
INDIRECT PHOTOLYSIS
Sensitizer:
Conc. of sensitizer:
Rate constant:Degradation:
Deg. product:
Method
:
Year
:
GLP
:
Test substance:
Method:ResultReliability

:
:

air
nm
based on intensity of sunlightOH
cm³/(molecule*sec)% afterother (measured)
1978
no dataother TS: p-cresol, no purity reported
smog chamber
Temp. 300 +-1 K
reference substances: n-butane, neopentane
initial TS concentration ca. 0.25 ppm for p-cresol
OH radical concentration: (1-4) x10E6 molecule cm-3
K[OH] = 52 +- 5 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction

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3. ENVIRONMENTAL FATE AND PATHWAYS

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions
10.05.2004(27) (28)TypeLight source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

10.05.2004

water
nm
based on intensity of sunlightnot measured
other (measured)
1995
no dataother TS: p-cresol, purity commercial, vacuum distilled
Determination of the photosensitized oxidation in water- Merry-go-round photoreactor DEMA (Hans Mangels GmbH, Bornheimroisdorf, Germany) Model 125- Light source: 700 W Hanau TQ718 medium pressure mercury lamp,
equipped with cut-off filter: lambda > 320 nm- Temperature 25 °C- Photon fluence density 1.7 mEinstein m-2 s-1 at 366 nm- Chemical analysis by HPLC, quantification at 285 nm
K = 0.0004 s-1
direct photolysis (in the absence of sensitizer) was
negligible- Test system: merry-go-round photoreactor- Concentration of test substance: 2.5 µM- Concentration of sensitizer: humic acid (DOC = 1.65 mg/l)- temperature: 25 degrees C(3) invalid
Quantification of environmental reaction rate not possible
(29)

Type
Light source
Light spectrum
Relative intensity
Conc. of substanceDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

water
Sun light
290 nmbased on intensity of sunlight
1 mg/l at °C

Method:Result:Determination of rate constants for photolysis in aqueous
solution in the absence and presence of humic acids
A photolysis halflife of 35 days was determined, while withaddition of 9.5 ug/l humic acid the half-life was 3 days.

Test condition:

Reliability:

10.05.2004
Type

200

:

other (measured)
1978
noother TS: m-cresol, no purity reported by Choudry

The authors report computer simulated estimated half-lives for different
compartments (river: 200 d, eutrophic pond: > 400 d, eutrophic lake > 400
d, oligotrophic lake 100 d)
Sunlight, in April (mostly overcast)pure water, with and without humic acid (9.5 ug/ml)
tubes held in rack at 60 ° angle to the horizon(2) valid with restrictions
Basic data given(30) (31)water

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYSLight source
Light spectrum
Relative intensity:::

Result:Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

nm
based on intensity of sunlight
The rate constant of hydroxyl radicals reaction is 1.2 E10
1/M/sec(4) not assignable
Secondary literature

02.10.2001
3.1.2

(32)

STABILITY IN WATER

Remark:Reliability:

Flag
09.01.2003

:

3.1.3

Based on the chemical structure of the compound hydrolysis
is not expected under temperature and pH values occuring in
the environment.
(2) valid with restrictions
Expert judgement
Critical study for SIDS endpoint

STABILITY IN SOIL

TypeRadiolabel
Concentration
Soil temperature
Soil humidity
Soil classification
Year
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

laboratory
°C

1990
no
other TS: p-cresol, no purity reported
Bench-scale experiments with contaminated soil.
Determination of passive evaporation and biodegradation ofcresolspassive evaporation half-life 4.2 - 4.8 weeks
biodegradation: after 4 days below detection limit
Passive evaporation: plastic petri plates (88x18 mm) placedon canopy-covered table. Temp. 10-17 degrees C, humidity 75%
Shake-flask biodegradation test: 8-25 g soil mixed with 50
ml buffer solution; shaken for 4 days
(3) invalid
Methodological deficiencies

07.05.2004
3.2.1

MONITORING DATA

3.2.2

FIELD STUDIES(33)

UNEP PUBLICATIONS

201

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
3.3.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

volatility
water - air% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: measured
1987

Method:Result:Reliability:

Flag
10.05.2004:

Data were taken from 2 sources- Gaffney JS, Senum GI (1984) In: Newman L (ed.) Gas-Liquid Chemistryof Natural Waters. Brookhaven National Laboratory, Upton, NY, pp. 5-1 to
5-7- Lind JA and Kok GLJ (1986) J. Geophys. Res. 91, 7889-7895
Henry's law constant (25 degrees C):
H = 0.1 Pa.m3.mol-1(2) valid with restrictions
basic data given
Critical study for SIDS endpoint
(34)

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

adsorption
water - soil
% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: batch equilibrium method, similar to OECD Guideline 106
1982

RemarkResult
Test condition:::

Reliability:

Flag
10.05.2004:

Koc determined for clay loam soil
Koc = 48.66
Soil: Brookston clay loam soil, collected from top 15 cm,
air-dried, 5.10% organic matter, pH 5.7
soil/solution ratio 1:10
TS concentrations 5, 10, 20, 30, 50 mg/l, deoxygenated bypurging with N2
triplicate samples, temp. 20+-1 degrees C, incubation period 24 h(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with general accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

adsorption
water - soil
% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: batch equilibrium method
1986

Remark:The authors presume that the high adsorption factors obtained in the study

202

(35)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

for low OC soils could be attributed to H-bond interactions between
phenolic hydroxyl and clay surfaces (clay-content in these soils: 68% and86%).

Result
Test condition::

Reliability:

10.05.2004

This type of adsorption can't be applied to explain the adsorption
phenomenon (correlation between OC-content and adsorption), whichusually occures in standard soils.
Koc = 3420 (Apison), 3350 (Fullerton), 115 (Dormont)
3 soils tested: Dormont (pH 4.2; OC 1.2%), Apison (pH 4.5;
OC 0.11%), Fullerton (pH 4.4; OC 0.05%)
soil/water ratio 1:1 - 1:66
initial TS concentration 0.5 - 1.0 mg/l
incubation period 24 h(3) invalid
No standard soil was used in the test. Soils Apison and Fullerton have avery low OC-content.Suggested OC-content in OECD 106:0.6-3.5%; in
67/548/EEC C.18: >0.3%) ).
(36)

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

adsorption
water - soil
% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)

Remark:Reliability:

the authors cite a log Koc of 2,70 (koc 501), but no details on theexperiments are described nor the primary citation is given(4) not assignablesecondary literature, experimental details missing

15.01.2003

(37)

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

adsorption
water - soil
% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)

Result:Neither Freundlich adsorption coefficients nor Koc values are reported in
the article. The authors report the isotherms in graphic formate.
In the Chemfate database citation of this article Freundlich adsorption
coefficients (K) are estimated from the isotherms at about 50 ppm: 0.50
E02 to 0.5 E01.
The corresponding Koc values can be calculated as 560 to 10000.
No explanation for the wide variety of the adsorpion coefficients is given.

Test condition:

Reliability:

5 soils were tested: Davidson (pH 6.4; OC 0.3%), Molokai (pH 6.2; 0.5%),
Fanno (pH 7.0; OC 0.9%), Mohave (pH 7.8; OC 0.4%), Ava (pH 4.5; OC
0.4%)
200 ml deionized water were added to 10 g of soil
initial TS concentration 5 - 100 ppm
temperatur 22 °C
equilibration time 5 days
(3) invalid

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

No standard soil was used in the test. The five soils have a very low OCcontent (0.3-0.9 %).Suggested OC-content in OECD 106:0.6-3.5%; in
67/548/EEC C.18: >0.3%)).
The isotherms are reported in five graphs, but the logarithmic scale is notlabeled correctly.
(38) (39)15.01.2003
3.3.2

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

DISTRIBUTION

Media
MethodYear:::

air - biota - sediment(s) - soil - waterCalculation according Mackay, Level I
2001

Result:

Test condition:

Calculated distribution between environmental compartments:
Air:
2.46 %
water:
96.26 %
soil:
0.66 %
bottom sediment: 0.62 %suspended sediment: 0.001 %biota:
0.0004 %data used in calculation
temperature (°C):
25molar mass (g/mol): 108.14
vapor pressure (Pa): 14.7
water solubility (g/l): 21.5
log Kow:
1.94

Reliability:

Flag
13.05.2003:

volumes in unit world (m3)air:
6 000 000 000
water:
7 000 000
soil:
45 000sediment:
21 000susp. sediment:
35
biota (fish):7(2) valid with restrictions
Generally accepted calculation method
Critical study for SIDS endpoint
(40)

3.4

MODE OF DEGRADATION IN ACTUAL USE

3.5

BIODEGRADATION

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

204

aerobic
activated sludge, domestic
100 mg/l related to Test substance
related to
80 - 95 (±) % after 40 day(s)readily biodegradable
other: comparable to OECD Guideline 301C
1981
noother TS: p-cresol, purity at least 99 % (obtained from Aldrich Chemicalcompany)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Method:Remark:Result:

Test condition:

Reliability:

Flag
11.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Result:

Test condition:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Initial sludge concentration 30 mg dw/l
reference compound aniline
Incubation period 20-40 days; no oxygen uptake curve given;degradation of reference substance aniline >=60 % within 28 days
The oxygen uptake curves are not reported. However, the authors statethat all test compounds revealed the lag phase, biodegradation phase andthe plateau region within a period of 10 days, indicating that the 10-day
window criteria is met.
first order biodegradation constant (hr-1): ln k = -5.87
maximum specific substrate uptake rate per unit biomass km = 18.5 / day(Aniline 16.1, Phenol 16.9)
p-Cresol is slightly better biodegradable than phenol and aniline
Inoculum /test organism- Type of sludge: activated- Source: municipal treatment plant, receiving predominantly domestic
sewage- Initial cell concentration: 30 mg/l
Test system- Culturing apparatus: Sapromat- Closed vessels used: yes
Initial test substance concentration: 100 mg/l
Duration of the test: 20-40 days
Test conditions- Composition of synthetic medium: OECD
- Test temperature: 25 degrees C
Reference substance: aniline 100 mg/l(2) valid with restrictions
Study comparable to OECD Guideline 301C
Critical study for SIDS endpoint(41)
aerobic
other: natural microorganism communities from water and sediment
200 µg/l related to Test substance
related to
50 - 100 (±) % after 43 hour(s)1983noother TS: p-cresol, no purity reported [ring-U-14C] p-cresol
Biodegradation in natural aquatic test systems:
1.shake-flasks with water, 2.shake flasks with water andsediment, 3.intact sediment-water cores (eco-cores)
3 sample sites in a river estuaryFirst order half-lives:water flasks: 9.5-43 h
sediment flasks: 5.9-11 h
eco-core:
3.0-16 h
1. shake flask tests with filtered water
2. shake flask tests with filtered water and 500 mg/lorganic sediment (30-50% OC). Sediment collected from the
top 5 cm of the sediment surface
3. Eco-core samples had an aerobic layer of detritus
overlying anaerobic sediment.
All flasks incubated with radiolabelled TS and maintained at
18 degrees C in the dark
Analysis: water samples filtered and analysed by HPLC,UNEP PUBLICATIONS

205

OECD SIDS
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Reliability:

Flag
24.05.2004:

Type
Inoculum
Contact time
Degradation
ResultDeg. product
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result
Test condition::

Reliability:

Flag
24.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Result
Test condition::

Reliability:

Flag
24.05.2004:

Type
InoculumDeg. product
Method

:
:
:
:

206

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

measurement of 14CO2 radioactivity(2) valid with restrictions
No standard procedure but in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint(42)
aerobic
activated sludge, industrial= 100 (±) % after 10 day(s)inherently biodegradable
OECD Guide-line 302 B "Inherent biodegradability: Modified Zahn-Wellens
Test"
1990
no dataother TS: p-cresol, no purity reported
90 % degradation during the log-phase (8 days)
Test substance conc. 50-400 mg/l DOC, 200-1000 mg/l COD
acclimatization phase 2 days(2) valid with restrictions
Guideline study, basic data given
Critical study for SIDS endpoint(43)
aerobic
activated sludge, adapted
200 mg/l related to COD (Chemical Oxygen Demand)
related to= 96 (±) % after 5 day(s)inherently biodegradable
other: batch system (similar to OECD 302B "Zahn-Wellens-Test")
1976
no dataother TS: p-cresol, no purity reported- Test compound was sole source of carbon- Inoculum density: 100 mg dry matter/l; gradual increase of TS
concentration during 20 days adaptation period- COD measured- With volatile substances a test without inocculum was done todifferentiate the actual biological degradation from the losses due to mere
volatilization
Initial degradation rate: 55.0 mg COD/g/h
20 +/-3 degree C; pH 7.2; mineral salts medium; dark;
continuously stirred(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
basic data given
Critical study for SIDS endpoint(44)
anaerobic
anaerobic sludge
yes

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Year
GLP
Test substanceDeg. products

:
:
:
:

1981
no
other TS: p-cresol, no purity reported
74-82-8 200-812-7 methane

Method:Result:

Test condition:

Reliability:

Flag
07.05.2004:

primary anaerobic sludge from 12 treatment plants receiving
mainly domestic waste water were diluted to 10% in a mineralsalts medium, test substance concentration 30 mg/l;
secondary anaerobic sludge from 2 treatment plants diluted
to 10% in a mineral salts medium, test substance 50 mg/l
incubation for 8 weeks; triplicate samples
primary sludges:
degradation ranged from 62 to 101% in 11 sludges (lag times
for approx. 20% of theoretical CH4 production: 2-5 weeks;
insufficient data for 1 sludge
secondary sludges:
degradation was 51% after 4 weeks lag-phase with the firstsludge and 121% after 3 weeks lag-phase with the second(degradation related to theoretical methane and CO2
production)
35 degrees C, due to storage of sludges before incubation, lag phase of
methanogenesis could be increased in some sludges(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint
(45)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition
Reliability

:
:

Flag
07.05.2004:

Type
Inoculum
Concentration:::

anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
56 day(s)(±) % after
yes
1984
no
other TS: p-cresol, no purity reported
74-82-8 200-812-7 methane
primary and secondary anaerobic sewage sludge from 9
treatment plants diluted to 10% in a mineral salts medium;
degradation measured as gas pressure increase
data have been published by the authors as a NTIS-study (previous data
set)
in 2 different secondary sludges >75% degradationin 9 different primary sludges degradation 62-101%
incubation for 8 w at 35 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint(46)
anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to

UNEP PUBLICATIONS

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OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Deg. products:

Method:Result:

Test condition:

Reliability:

Flag
07.05.2004:

Type
Inoculum
Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Method:RemarkResult::Reliability

:

yes
1988
no
other TS: p-cresol, of highest purity available (obtained from Aldrich
Chemical Co.)
74-82-8 200-812-7 methane
primary anaerobic digesting sludge receiving a mixture ofdomestic and industrial waste waterlag time 7 days
net total gas production was 96 +/- 4.3 % of the theoretical production(CH4 + CO2)
- medium 2-3 g dw/l sludge- incubation for >= 60 d at 35 degrees C- 3 replicates- sterile controls for abiotic gas production- gas production measured with hand-held pressure meter(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint(47) (48)aerobic
aerobic microorganisms
120 hour(s)(±) % after
40 hour(s) ca. 50 %70 hour(s) ca. 90 %%%%not measured
1982
noother TS: p-cresol, ring-U-14C-labelled
Adaptation of natural microbial communities was measured in
ecocore test systems filled with sediment and natural watercollected at a river.
Parent compound disappearance and mineralization weremonitored.
degradation values taken from a graphics
Mineralization was rapid without a lag-phase. Pre-exposure
did not accelerate degradation.
(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail24.05.2004
Type
InoculumDeg. product
MethodYear
GLP
Test substance208

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

(49)
:
:
:
:
:
:
:

aerobic
other: marine bacteria
not measured
other: batch culture study in seawater
1992
noother TS: p-cresol, purity >98%

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Method:Result:

Test condition
Reliability::

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Seawater from California (USA) supplemented with 100, 500,
and 1000 µg/l test substance. Analysis of subsamples with
GC/MS
t1/2 = 295 h (100 µg/l)
t1/2 = 215 h (500 µg/l)
t1/2 = 325 h (1000 µg/l)
Doubling time of population
85 h (100 µg/l)
40 h (500 µg/l)
31 h (1000 µg/l)
Temp. 20+-2 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail24.05.2004

(50)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Result:

Test condition
Reliability::

aerobic
other: mixed microbial cultures
1.6 mg/l related to Test substance
3.2 mg/l related to Test substance
8 day(s)(±) % after
other: APHA method (1980)1988
noother TS: p-cresol, no purity reported
BOD technique; determination of the degradation rate
constant which is compared with those reported for natural
watersPseudo-first-order rate constants (1/h):
Degradation of p-cresol in BOD test solution 0.028
Degradation of p-cresol in 5 natural waters 0.025 - 0.106 (mean 0.063)
For comparison:
Degradation of phenol in BOD test solution 0.020
Degradation of phenol in 5 natural waters 0.046 - 0.110 (mean 0.075)
p-Cresol is nearly as biodegradable as phenol.
2.3 E8 cells/ml; 21 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail10.05.2004

(51)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result:aerobic
other: mixed microbial cultures
1.6 mg/l related to Test substance
3.2 mg/l related to Test substanceother: BOD technique1989
noother TS: p-cresol, no purity reported
study targets to determine the effect of inoculum
density on biodegradation rate; BOD techniquedegradation rate was nearly independent on biomass
concentration. First order rate constant 3.4 (+/- 0.24) x 10-1/day with 2.3

UNEP PUBLICATIONS

209

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Test condition:

Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

E4 cells/l and 4.0 (+/- 0.02) x 10-1/day with 2.3 E8 cells/l
21 +- 3 degrees C
5 inoculum concentrations between 2.3 E4 and 2.3 E8 cells/l(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(52)

Type
InoculumDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

aerobic
other bacteria: natural aquatic microbial assemblages

Method:Result:

Test condition
Reliability::

Determination of degradation kinetics over a large
concentration range
Tests performed in freshly collected water from a lake, aswamp surface, and seawater.
Date
Site TS Concentr.[µg/l] Vmax[µg/l/d]June 1986 Lake 1-10000
11
Dec. 1986 Lake 1-100000
36
Febr. 1987 Lake 1-10000
1.3-176
Oct. 1986 Sea
1-500
0.06-0.8
Dec. 1986 Swamp 1-100000
40
incubation at 25 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail1986
noother TS: U-14C-labeled p-cresol

07.05.2004

(53)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

MethodResult
Test condition
Reliability

:
:
:
:

aerobic
other: groundwater microorganisms
2.1 mg/l related to Test substance
related to
no
1985
no
other TS: p-cresol, no purity reported
Degradation of TS in surficial groundwaterComplete degradation within 5-8 days, lag phase 2 days
pH 5.3; 20 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail24.05.2004
Type
Inoculum
Contact time
Degradation
ResultDeg. product
Method
Year
GLP

210

(54)
:
:
:
:
:
:
:
:
:

anaerobic
anaerobic sludge> 100 (±) % after 15 day(s)inherently biodegradable
yesother: Handbook
1983
noUNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test substanceDeg. products::

other TS: p-cresol, purity not noted
74-82-8 200-812-7 methane

RemarkResult::

Test condition:

Reliability:

sensitivity of acid formers and methanogenic consortia examined
Mineralization occurred after 15 days at a concentration of
100 ppm p-cresol. Duration of mineralization increased to 39 days at aconcentration of 400 ppm p-cresol.
TS concentrations: 200, 400, and 1000 mg/l
incubation for 6 weeks at 37 degrees C(4) not assignable
No standard test procedure, but in accordance with generally acceptedscientific standards, not relevant for purpose of HPV program

24.05.2004

(55)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Result:

Test condition
Reliability::

aerobic
other: acclimated mixed microbial culture.4 mg/l related to Test substance
3.2 mg/l related to Test substance
20 day(s)(±) % after
other: APHA 19801987
noother TS: p-cresol, no purity reported
BOD (5 days) = 5.63 mmol O2/mmol TS
ThBOD = 8.50 mmol O2/mmol TS
21 +- 3 degrees C(4) not assignable
Documention insufficient for assessment

24.05.2004

(56)

Type
InoculumDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

aerobic
other bacteria: Aufwuchs communitiy
not measured

Method:Result:Reliability:

Estimation of biotransformation kinetics in natural waters.
Aufwuchs colonized for 5 months on Teflon strips at 2 rivers and 2 ponds.
Strips were returned to laboratory, andfastened into a beaker containing autoclaved natural water.
Beakers spiked with 100 and 200 µg/l test substance at 20
degrees C. TS detected by HPLC.
A great variability for the k values (for individual sample
sites between -5.1 and -3388 h-1) was found. Mean values for the sites:
pond 1: k = -273.1 h-1
pond 2: k = -95.5 h-1
river 1: k = -1637.1 h-1
river 2: k = -70 h-1(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(57)

11.05.2004
Type

:

1987
no
other TS: p-cresol, purity at least 99 %aerobic

UNEP PUBLICATIONS

211OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Inoculum:

Concentration:

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

ResultReliability::

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

other bacteria: acclimatized mixed culture of pentachlorophenol-degrading
bacteria
5 mg/l related to Test substance
related to
29 day(s)90 (±) % after 36 hour(s)28 hour(s) = 50 %36 hour(s) = 90 %%%%other: Die-away Test
1990
noother TS: p-cresol, gas chromatographic grade
no lag phase(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail24.05.2004

(58)

Type
InoculumDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

anaerobic
other: anaerobic sludge of a wastewater treatment plantnoMethod:Result:

Test condition
Reliability::

Simulation of anaerobic digestion of primary and secondary
sludge; digesters fed with spiked sludge; analyticalmeasurements in sludge feed, digester mixed liquor, andmixed-liquor centrate
6% of the TS were detected in waste water, 20% sorbed onto
solids, and 74% were degradedsludge retention time 30 days; 35 +- 1 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail1989
noother TS: p-cresol, no purity reported

11.05.2004

(59)

Type
InoculumDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

anaerobic
other: anaerobic sludge from a municipal treatment plant

Method:Result:Reliability:

Pilot scale anaerobic digester fed with sludge from amunicipal treatment plant
Overall removal 99.5%
Primary digester removal 96.6%
Secondary digester removal 85.7%
Secondary supernatant residual 0.1%
Secondary sludge residual 0.4%
(2) valid with restrictions
No standard test procedure, but in accordance with generally accepted212

other: pilot plant study
1994
other TS: p-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

scientific standards and described in sufficient detail07.05.2004

(60)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

anaerobic
anaerobic microorganisms
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
not measured
1995
noother TS: p-cresol, analytical grade
74-82-8 200-812-7 methane
Biodegradation under methanogenic conditions.
Inoculi: anaerobically digested sludge from a treatment
plant reveiving mainly domestic waste water, a freshwater
swamp, and a marine sedimentdegradation 30-75% in sludge, >75% in swamp (lag time <5weeks), 30-75% in sediment (lag time <10 weeks)
resuts expressed as % of complete mineralization to CH4 andCO2incubation 56 days (slusge and swamp) resp. 96 days
(sediment); 35 degrees C in the dark(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

(61)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

07.05.2004
Type
Inoculum::

Concentration:

anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
yes
1982
no
other TS: p-cresol, purity > 95 %
74-82-8 200-812-7 methane- Sludge from 2 municipal plants- Methane production monitored- HPLC to monitor dissapearance of substrate
Mineralization (related to theoretical methane and CO2
production) was 51% after 4 weeks with the first sludge and
100 % after 3 weeks with the second.
Experiment was also done with freshwater lake sediment but nodegradation was observed within 29 weeks
incubation at 35 degrees C in the dark, 10 % sludge inoculum, duplicate
tests(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(62)
anaerobic
other bacteria: acclimatized mixed culture of pentachlorophenol-degrading
bacteria
5 mg/l related to Test substance
related to

UNEP PUBLICATIONS

213

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

29 day(s)(±) % after
144 hour(s) <= 10 %166 hour(s) = 50 %200 hour(s) = 90 %%%other: Die-away Test
1990
noother TS: p-cresol, gas chromatographic grade(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(58)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

MethodResult::

Test condition
Reliability::

07.05.2004

anaerobic
anaerobic sludge
400 mg/l related to Test substance
800 mg/l related to Test substance
yes
1985
no
other TS: p-cresol, no purity reported
74-82-8 200-812-7 methane
Anaerobic batch study
Complete metabolism was observed only after acclimation
through repeated refeeding of substrate over a period of 5-8 months. The
rates of substrate metabolism and gas
production, however, was about equal in early (refed 3 or
fewer times) and in acclimated (refed 4-8 times) cultures.
After 35 days incubation the total gas production was 89%
and the CH4 production 134% of the theoretical amount.
37 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail
(63)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Deg. products

:

1986
no
other TS: p-cresol, no purity reported (Aldrich Chemical Co.) (methyl 14C
labelled from Pathfinder Lab.)74-82-8 200-812-7 methane

Result
Test condition::

Most of the methyl carbon of p-cresol (92 %) was oxidized to CO2.
preincubation for 2-3 months

214

anaerobic
other: anaerobic sludge, adapted
300 mg/l related to Test substance
related to
100 (±) % after 6 day(s)yesUNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

incubation for 20 d at 37 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(64)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Result:

Test condition:

Reliability:

anaerobic
other: municipal sewage sludge from primary anaerobic digesters
50 mg/l related to Test substance
related to
56 day(s)100 (±) % after 21 day(s)1983noother TS: p-cresol, no purity reported
74-82-8 200-812-7 methane
substance disappeared completely after 3 weeks
net CH4 production >90% of theoretical value
no transformation products observed
mineral salt medium with 10% sludge
Temp. 35 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(65)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Result:

Test condition:

Reliability:

07.05.2004
Type
Inoculum
Concentration:::

Deg. product:anaerobic
other: phenol-enriched metanogenic culture
100 mg/l related to Test substance
related toca. 100 (±) % after 192 hour(s)
yes
1988
no
other TS: p-cresol, no purity reported
74-82-8 200-812-7 methane
lag time 70 h, complete disappearance after 192 h, the CH4
production was 90% of the theoretical production
nominal test concentrations p-cresol 50, 100, 150, 250, 300, 400, 500, and
700 mg/l + phenol 200 mg/l
incubation at 35 degrees C with continuous shaking(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(66)
anaerobic
other: anoxic lake sediment.1 mg/l related to Test substance.8 mg/l related to Test substance

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OECD SIDS
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MethodYear
GLP
Test substance

:
:
:
:

Result
Test condition::

Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

1982
noother TS: p-cresol, purity > 95 %after 29 weeks no significant CH4 or CO2 formation observed
incubation at 20 degrees C in the dark with occasional
shaking(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004

(62)

Type
InoculumDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

anaerobic
other: aquifer from a river-groundwater infiltration site, adapted to m-xylene

MethodResult::

Test condition
Reliability::

Laboratory aquifer column; analysis of influent and effluent by HPLC
TS influent conc. 0.19 mM
TS effluentconc. <0.01 mM
continuous flow, 30 degrees C, microorganisms adapted to m-xylene(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail1987
noother TS: p-cresol, purity ar least 98 % (obtained from Fluka AG, Buchs,
Switzerland)

07.05.2004

(67)

Type
InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:

anaerobic
other: shallow anaerobic alluvial sand aquifer
yes

Method:Result:

Test condition:

Reliability:

2 +sites: 1 methanogenic, 1 sulfate-reducing
both aquifers receive leachate from a municipal landfill
lag time <10 days under sulfate-reducing and 46-90 days
under methanogenic incubations, no data for complete degradation given.
Degradation under sulfate reducing conditions postulated to stout withoxidation of methyl group
test medium: 50 g [wet weight] of aquifer solids and 50 ml
of groundwater
incubation at room temperature in the dark, quadruplicate
samples, preincubation 5 days, addition of 150 to 200 µM
test substance(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(68)07.05.2004
Type
Inoculum

216

:
:

1986
no
other TS: p-cresol, no purity reported (obtained from Aldrich Chemical Co.)p-hydroxybenzaldehyd
99-96-7 202-804-9 4-hydroxybenzoic acidanaerobic
other: undefined methanogenic consortia from river sediment

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Concentration:

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

07.05.2004
Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Method:Result:

Test condition
Reliability::

07.05.2004
Type
Inoculum
Concentration:::

Contact time
Degradation
Result:::p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

54 mg/l related to Test substance
related to
yes
1989
no
other TS: p-cresol, no purity reported
74-82-8 200-812-7 methane
black anoxic mud collected from a river inoculated in amineral medium (10% w/v)
non-acclimated consortia: turnover rate 3.00 µmol/day/g
sediment dw (lag-phase 12 d)acclimated consortia: turnover rate 6.00 µmol/day/g sediment dw (lagphase 0 d, based on a 24 days incubation period), the CH4 production was
97% of the theoretically possible yield
incubation at 28 degrees C in the dark
cultures were refed with 60 mg/l test substance every 2-4 w
for a total of 18 months(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail(69)
anaerobic
other: unacclimated sediments
1 mmol/l related to Test substance
related to
100 (±) % after 30 day(s)
yes
1990
no
other TS: p-cresol, no purity reported (obtained from Aldrich)
123-08-0 204-599-1 4-hydroxybenzaldehyde
65-85-0 200-618-2 benzoic acid74-82-8 200-812-7 methane
99-96-7 202-804-9 4-hydroxybenzoic acid
Sediment samples from a freshwater pond; degradation tested
under three reducing conditions: denitrifying, sulfidogenic, andmethanogenic
TS was completely utilized within 21 to 30 days in unacclimated sediment.
p-Cresol degradation proceeded through p-hydroxybenzaldehyde and phydroxybenzoate under methanogenic and denitrifying conditions. Under
methanogenic conditions, also dehydroxylation to benzoic acid took place
30 degrees C in the dark(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(70)
anaerobic
other: acclimated sediments
1 mmol/l related to Test substance
related to
100 (±) % after 10 day(s)UNEP PUBLICATIONS

217

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

yes

Method:Result:

Test condition:

Reliability:

Sediment samples from a freshwater pond; degradation tested
under three reducing conditions: denitrifying, sulfidogenic, andmethanogenic
TS was completely utilized within 6 to 10 days in acclimated sediment. pCresol degradation proceeded through p-hydroxybenzaldehyde and phydroxybenzoate under methanogenic and denitrifying conditions. Under
methanogenic conditions, also dehydroxylation to benzoic acid took place- 30 degrees C in the dark
- head space gas in the methanogenogenic and sulfidogenic cultures:
CO2/N2 (30 %/70 %)- head space gas in the denitrifying cultures: argon- cultures were acclimated to p-cresol by 2 - 3 feedings of p-cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(70)

07.05.2004
Type
Inoculum
Concentration:::

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Reliability

:

1990
no
other TS: p-cresol, no purity reported (obtained from Aldrich)
123-08-0 204-599-1 4-hydroxybenzaldehyde
65-85-0 200-618-2 benzoic acid74-82-8 200-812-7 methane
99-96-7 202-804-9 4-hydroxybenzoic acidaerobic
activated sludge, domestic, non-adapted
30 mg/l related to Test substance
100 mg/l related to Test substance
1.5 day(s)(±) % after
2 day(s) = 100 %
%
%
%
%
yes
other: Sapromat test1972
noother TS: p-cresol, no purity reported(3) invalid
Insufficient documentation

07.05.2004

(71)

Type
Inoculum
Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Method:218

aerobic
other: soil microorganisms
100 (±) % after 1 day(s)
no
1966
no
other TS: p-cresol, no purity reported
Inoculation in a 1% suspension of silt loam

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

TS analyzed photometrically(3) invalid
Unsuitable test system

24.05.2004

(72)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

MethodResult::Reliability:

24.05.2004
Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Result:Reliability:

anaerobic
other: microcosm containing aquifer and ground water
8 mg/l related to Test substance
related toyes
1989
no dataother TS: p-cresol, no purity reported
74-82-8 200-812-7 methane
methanogenic conditions in a microcosm, presumably 10 °C
lag time 100 days, disappearance after approx. 180 d (values taken from agraphics)(3) invalid
Insufficient documentation(73)
aerobic
other: river water and sea water
10 mg/l related to Test substance
100 mg/l related to Test substance
3 day(s)5 - 100 (±) % after 3 day(s)other: cultivation method
1987
other TS: p-cresol, no purity reported in abstract
The authors assume the compound to be easily biodegradable:with 10 ppm: Biodegradation in river water = 100% (3 repl)
with 10 ppm: Biodegradation in sea water = 100% (3 repl)
with 100 ppm: Biodegradation in river water = 100% (1 repl)
with 100 ppm: Biodegradation in sea water = 5% (1 repl)(4) not assignable
Publication in Japanese, short abstract in English

24.05.2004

(74)

3.6

BOD5, COD OR BOD5/COD RATIO

3.7

BIOACCUMULATION

Species
Exposure period
Concentration
Elimination
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Oncorhynchus mykiss (Fish, fresh water)
6 hour(s) at 11 °C
3.82 µg/l
no
1985
no
other TS: p-cresol, purity > 98 % (supplied by Pathfinder Laboratories, St.
Louis)UNEP PUBLICATIONS

219

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Method:Result:

Test condition
Reliability::

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Determination of absorption rate across gills
Analytical measurements in inspired and expired water,
calculation of gill uptake efficiency
About 23% of the TS were taken up via the gills (value takenfrom a graphics)
1 fish per experiment(3) invalid
Only 1 fish tested, no BCF determined

07.05.2004
3.8

(75)

ADDITIONAL REMARKS

Memo

:

biodegradation under three different anaerobic (denitrifying, sulfidogenic,
methanogenic) conditions

Method:Result:

Test substance
Reliability::

biodegradation was studied with acclimated and unacclimated sedimet
samples from a freshwater pond
the proposed reaction pathway is: p-Cresol > p-hydroxybenzyl alcohol > phydroxybenzaldehyde > p-hydroxybenzoate for all three conditions. Under
methanogenic conditions, p-hydroxybenzoate reacts to benzoate withsubsequent ring fission. Under denitrifying and sulfidogenic conditions, phydroxybenzoate did not react to benzoate, immediate ring fission ispostulated.
other TS: p-cresol, no purity reported (Aldrich, Milwaukee, WI)(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(70)12.12.2002
Memo:biodegradation under anaerobic (sulfate-reducing) conditions

Method:Result:

Test substance
Reliability::

acclimated aquifer slurries (alluvial sand) amended with either Na2MoO4,
bromoethanesulfonic acid, or Na2SO4
HPLC measurements
the proposed reaction pathway is: p-Cresol > p-hydroxybenzyl alcohol > phydroxybenzaldehyde > p-hydroxybenzoate
other TS: p-cresol, no purity reported (obtained from Aldrich Chemical Co.)(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(68)12.12.2002
Memo:biodegradation under anaerobic (sulfate-reducing) conditions

Method:Result:

Test substance
Reliability::

Ring-14C-labeled p-cresol incubated with bacteria enrichedfrom the sulfate-reducing portion of an anoxic aquifer.
Periodical analysis of the enrichment by HPLC.
the proposed reaction pathway is: p-Cresol > p-hydroxybenzyl alcohol > phydroxybenzaldehyde > p-hydroxybenzoic acid. The pathway diverges
after p-hydroxybenzoic acid to form benzoic
acid and phenol.
Ring-14C-labeled p-cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail(76)

12.12.2002

220

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Memo:biodegradation pathway with activated sludge

Result:

Test substance
Reliability::

p-cresol is first hydroxylated to 4-methylcatechol andcleaved through meta-cleavage pathway.
p-cresol, no purity reported in abstract(4) not assignable
Publication in Japanese

12.05.2004

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(77)

UNEP PUBLICATIONS

221

OECD SIDS
4. ECOTOXICITY

4.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

ACUTE/PROLONGED TOXICITY TO FISH

Type
Species
Exposure period
Unit
LC50
EC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

flow throughPimephales promelas (Fish, fresh water)
96 hour(s)mg/l= 16.5= 16.5

Method:Result:

Test condition:

Reliability:

Flag
07.05.2004:

Fish (28 d old; mean lenght: 20.9 mm; mean weight: 0.134 g)
exposed in Lake Superior water; 5 TS concentrations in therange of 11.8 to 66.2 mg/l tested (plus control); number ofdead fish recorded every 24 h; observations of fish
behaviour and body morphology at regular intervals; TSanalysis by GLC
confidence limits (95%):
LC50 = EC50 = 15.9 - 17.0 mg/l
Affected fish lost schooling behaviour and swam near thetank surface. They were hyperactive and overreactive toexternal stimuli. They had increased respiration,
convulsions, and rigid musculature. Some hemorrhaging was
also apparent. They were deformed and lost equilibrium prior
to death.
24.1 degrees C; dissolved oxygen 7.0 mg/l; hardness 47.9 mg
CaCO3/l; alkalinity 44.1 mg CaCO3/l; pH 7.79
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

flow throughOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
= 7.9

RemarkTest condition::

lethargic at 5.6 mg/l
DILUTION WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- Conductance: 1212.3 µmhos/cm at 25 degrees C
TEST SYSTEM- Concentrations: 1:2 dilution series- Number of replicates: 2- fish per replicate: 10

222

yes
other
1985
no
other TS: p-cresol, purity at least 99 % (Aldrich Chemical Co.)

(78)

yes
EPA OPP 72-1
1974
no dataother TS: p-cresol, purity not noted

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004- Test temperature: 14 degrees C- Dissolved oxygen: 6.5 mg/l (84.5% of saturation)- pH: 8.1
- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint

Reliability:

Flag
22.10.2001:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

flow throughPimephales promelas (Fish, fresh water)
96 hour(s)mg/l= 28.6

RemarkTest condition::

Reliability:

Flag
22.10.2001:

Lethargic and loss of equilibrium at 22.7 mg/l
DILUTION WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- Conductance: 1212.3 µmhos/cm at 25 degrees C
TEST SYSTEM- Concentrations: 1:2 dilution series- Number of replicates: 2- fish per replicate: 10- Test temperature: 14 degrees C- Dissolved oxygen: 6.5 mg/l (84.5% of saturation)- pH: 8.1
- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticSalmo trutta (Fish, fresh water, marine)
96 hour(s)
mg/l
= 4.4

Method:Result:

Test condition:

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (6 h) = 4.7 mg/l
LC50 (24 h) = 4.4 mg/l
LC50 (48 h) = 4.4 mg/l
12 degrees C; reconstituted water

(79)

yes
EPA OPP 72-1
1974
no dataother TS: p-cresol, purity not noted

(79)

no
1969
no
other TS: p-cresol, purity of "practical grade"

UNEP PUBLICATIONS

223

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticSalvelinus fontinalis (Fish, estuary, fresh water)
96 hour(s)
mg/l
= 5.8

Method:Result:

Test condition
Reliability

:
:

Flag
07.05.2004:

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (6 h) = 8.5 mg/l
LC50 (24 h) = 6.3 mg/l
LC50 (48 h) = 5.8 mg/l
at concentrations of 6 to 20 mg/l, the approximate
incidences of surfacing were 90% during the first 10 minutes
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticCyprinus carpio (Fish, fresh water)
96 hour(s)mg/l= 13.3

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (24 h) = 22.0 mg/l
LC50 (48 h) = 15.0 mg/l
at concentrations of 15 to 23 mg/l, the approximate
incidences of surfacing were 80% during the first 10 minutes
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint
(80)

no
1969
no
other TS: p-cresol, purity of "practical grade"

(80)

no
1969
no
other TS: p-cresol, purity of "practical grade"

07.05.2004
Type
Species
Exposure period
Unit
LC50

224

(80)
:
:
:
:
:

staticIctalurus melas (Fish, fresh water)
96 hour(s)mg/l= 57.5

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:

Method:Result:

Test condition
Reliability

:
:

no
1969
no
other TS: p-cresol, purity of "practical grade"
10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (24 h) = 120.0 mg/l
LC50 (48 h) = 94.0 mg/l
during the first 10 minutes the fish did not surface at any
concentration
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(80)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticIctalurus punctatus (Fish, fresh water)
96 hour(s)mg/l= 39.7

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (6 h) = 65.0 mg/l
LC50 (24 h) = 58.0 mg/l
LC50 (48 h) = 50.0 mg/l
during the first 10 minutes the fish did not surface at any
concentration
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

no
1969
no
other TS: p-cresol, purity of "practical grade"

07.05.2004

(80)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticLepomis macrochirus (Fish, fresh water)
96 hour(s)
mg/l
= 7.1

Method:Result:10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (24 h) = 7.9 mg/l
LC50 (48 h) = 7.1 mg/l
at concentrations of 14 to 16 mg/l, the approximate

no
1969
no
other TS: p-cresol, purity of "practical grade"

UNEP PUBLICATIONS

225

OECD SIDS
4. ECOTOXICITY

Test condition
Reliability

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004::

incidences of surfacing were 30% during the first 10 minutes
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(80)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
= 7.4

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (6 h) = 11.4 mg/l
LC50 (24 h) = 9.2 mg/l
LC50 (48 h) = 8.4 mg/l
In an additional test under flow-through conditions, a
concentration of 10 mg/l caused a total incapacitation of
all tested 20 fish within 8.5 minutes
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

no
1969
no
other TS: p-cresol, purity of "practical grade"

07.05.2004

(80)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticPerca flavescens (Fish, fresh water)
96 hour(s)
mg/l
= 10

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (6 h) = 19.5 mg/l
LC50 (24 h) = 12.3 mg/l
LC50 (24 h) = 10.0 mg/l
at concentrations of 12 to 18 mg/l, the approximate
incidences of surfacing were 50% during the first 10 minutes
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

no
1969
no
other TS: p-cresol, purity of "practical grade"

07.05.2004
Type
Species
Exposure period

226

(80)
:
:
:

staticPimephales promelas (Fish, fresh water)
96 hour(s)UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

mg/l
= 15.5

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrol
LC50 (24 h) = 60.3 mg/l
LC50 (48 h) = 50.8 mg/l
at concentrations of 30 to 150 mg/l, the approximate
incidences of surfacing were 30% during the first 10 minutes
12 degrees C; reconstituted water(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

no
1969
no
other TS: p-cresol, purity of "practical grade"

07.05.2004

(80)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

flow throughOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
= 7.5

Method:Reliability:

Bioassays were conducted at 0 (control), 10, 18, 32, 56, and100% of the maximum test concentration. Ten fish were
exposed at each concentration. The fish weighed between 1
and 4 g each. Bioassays were repeated 3 times. Chemicals
were added to the water by a Hamilton Syringe pump to create
the 100% concentration. Dilutions were done by aMount-Brungs diluter. Each bioassay tank contained 14
liters of water and the flow per tank varied between tests
from 21 to 111 ml/min, depending upon how much chemical wasavailable. The tanks were not aerated, to reduce
volatilization. The levels in water of most water-soluble
test compounds were measured daily. The assay method was
the measurement of the absorbance of the ultraviolet lightby the test solutions in a quartz cell with a 1 cm path
length. Concentrations were calculated by reference tostandard curves of the chemical dissolved in the control
tank water.
(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

yes
other
1984
no dataother TS: p-cresol, purity not noted

07.05.2004
Type
Species
Exposure period
Unit
Limit test
Analytical monitoring

(81)
:
:
:
:
:
:

flow throughPimephales promelas (Fish, fresh water)
96 hour(s)noUNEP PUBLICATIONS

227

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

MethodYear
GLP
Test substance

:
:
:
:

MethodResult::

Test condition:

Reliability

:

1984
no
other TS: p-cresol, no purity reported
Determination of sublethal endpoints with fish larvae
concentrations up to 4.2 mg/l had no significant effect onlarval survival or growthlarval RNA, DNA and protein content, although reduced at
2.57 mg/l, was not significantly affected at any
concentration
Larval fish within 24 h of hatching, 25-35 per chamber
medium: soft Lake Superior water
5 TS concentrations, range 0.4-4.2 mg/l(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
water chemistry data not reported

07.05.2004

(82)

Type
Species
Exposure period
Unit
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

semistatic
other: Lepidocephalichthys guntea (freshwater fish)
96 hour(s)mg/lResult:

Test condition:

Reliability:

LC50 (24 h) = 21.0 (16.42 - 26.86) mg/l
LC50 (48 h) = 18.0 (14.70 - 22.03) mg/l
LC50 (72 h) = 16.0 (13.20 - 19.39) mg/l
LC50 (96 h) = 14.0 (11.82 - 16.58) mg/l
fish lenght 5.16 +- 0.38 cm, weight 1.46 +- 0.27 g
27-29 degrees C; pH 7.0-7.3; oxigen 7.0-7.2 mg/l; hardness
80-86 mg/l CaCO3
10 fish/concentration
medium renewed daily(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detailnoother: see test conditions
1998
noother TS: p-cresol, analytical grade

07.05.2004

(83)

Type
Species
Exposure period
Unit
EC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticGadus morrhua (Fish, fresh water)
96 hour(s)mg/l=5Method:Result:Effect endpoints: death, pathology, inhibition of cleavage
and differentiation, pigment defects
parallel test with larvae (6 days after hatching) showed

228

yes
1985
no
other TS: p-cresol, purity > 98 % as determined by GC (obtained from
Merck)UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test condition:

Reliability:

pigment effects at 1 mg/l
5 degrees C
TS concentration stable during the test period(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(84)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticPimephales promelas (Fish, fresh water)
96 hour(s)
mg/l
= 19

Result:

Test condition:

Reliability:

LC50 (1 h) = 30 mg/l
LC50 (24 h) = 26 mg/l
LC50 (48 h) = 21 mg/l
LC50 (72 h) = 21 mg/l
concentrations are nominal values
endpoint: complete immobilization, equated to deathO2 was =< 4 mg/l during the test
Lake Superior Water; 18-22 degrees C
10 fish per concentration, fish 4-8 weeks old, length
1.1-3.1 cm(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

no
1976
no
other TS: p-cresol, no purity reported (obtained from Curtin Matheson
Scientific Inc.)

07.05.2004

(85)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticGambusia affinis (Fish, fresh water)
96 hour(s)mg/l
33 calculatednonoother: see test conditions
2000
no dataother TS: p-cresol, no purity reported

Test condition:

Reliability:

Test medium: dechlorinated one day old tap water, medium renewed daily.
3 replicates and control.
10 fish were exposed to each concentration from 30-40 mg/l.
Temperature: 25-27°C.
pH: 7.2-7.6.
(2) valid with restrictions
Basic data given(86)

07.05.2004
Type
Species
Exposure period
Unit

:
:
:
:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)mg/lUNEP PUBLICATIONS

229

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

LC0
LC50
LC100
Limit test
Analytical monitoring
Method

:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability

:

= 10
= 11
= 13
no
other: Test Procedure of the Abwasserabgabengesetzentwurf (Deutscher
Bundestag 1974)1982
noother TS: p-cresol, no purity reported(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(87)

Type
Species
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

MethodResult::Reliability:

Leuciscus idus melanotus (Fish, fresh water)
4 hour(s)other: DIN 38412 (20) (1981)1986
noother TS: p-cresol, no purity reported
Endpoints: activity of the transaminases GOT and GPT
acticity of both enzymes increased at concentrations of 5
mg/l, no change at 8 mg/l, increase at 10 and 12 mg/l
(3) invalid
No clear dose-response relationship07.05.2004

(88)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticother: Oreochromis mossambicus (freshwater fish)
96 hour(s)
mg/l
28
no
no
other: see test conditions
2001
no dataother TS: p-cresol, no purity reported

Reliability:(3) invalid
Insufficient documentation

07.05.2004

(89)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

230

Rutilus rutilus (Fish, fresh water)
24 hour(s)
mg/l
= 17
1959
other TS: p-cresol, no purity reported
results from: Albersmayer & Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
Study does not follow any guideline. No analytical monitoring, noinformation about the test substance. Further details are missing

07.05.2004

(90)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Test condition:

Reliability:

Cyprinus carpio (Fish, fresh water)
24 hour(s)
mg/l
= 21
1959
other TS: p-cresol, no purity reported
results from: Albersmayer & Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)
Temperature: 18°C
O2 Content in water: 8 mg/l
Number of animals per test vessel: 10
Effect concentrations for each replicate (LC50) were derived in acoordinate system and finally a mean value was calculated(3) invalid
Study does not follow any guideline. No analytical monitoring, noinformation about the test substance. Further details are missing

07.05.2004

(90)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

Tinca tinca (Fish, fresh water)
24 hour(s)
mg/l
= 16
1959
other TS: p-cresol, no purity reported
results from: Albersmayer & Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analytical monitoring, noinformation about the test substance. Further details are missing

07.05.2004

(90)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)
mg/l
=4
no
other: Mann, H., Fischtest mit Goldorfen zur vergleichenden Pruefung derakuten Toxizitaet von Wasserinhaltsstoffen und Abwaessern, Praktische
Erfahrungen aus 3 Ringtesten, Z. f. Wasser- u. Abwasser-Forschung 9,103-109 (1976)1978
noother TS: p-cresol, no purity reported(4) not assignable
Secondary Literature

12.05.2004(19)

UNEP PUBLICATIONS

231

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

RemarkReliability::

Oncorhynchus mykiss (Fish, fresh water)
96 hour(s)mg/l
8.6
no data1977
noother TS: p-cresol, no data on purity available
Personal communication(4) not assignable
Literature not available

07.05.2004
4.2

(91)

ACUTE TOXICITY TO AQUATIC INVERTEBRATESTypeSpecies
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

flow through
Daphnia pulicaria (Crustacea)
48 hour(s)mg/l= 22.7yes
EPA OPP 72-2
1974
no dataother TS: p-cresol, purity not noted

Test condition:

Reliability:

Flag
22.10.2001:

DILUTION AND TEST WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- pH: 8.1
- Oxygen content: 6.5 mg/l (84.5% of saturation)- Conductance: 1212.3 µhos/cm at 25 degrees C- Number of replicates, individuals per replicate: 10- Test temperature: 14 +- 1 degrees C- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
EC0
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticDaphnia magna (Crustacea)
24 hour(s)
mg/l
= 2.5
= 4.9
no
other: DIN 38412 part 11
1988
noother TS: p-cresol, no purity reported

Remark:nominal values

232

(79)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test condition:

Reliability:

Flag
07.05.2004:

Type
Species
Exposure period
Unit
EC0
EC50
EC100
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

staticDaphnia magna (Crustacea)
48 hour(s)
mg/l
= 3.1
= 7.7
= 12.5noother: DIN 38412, part 11
1989
noother TS: p-cresol, no purity reported

Result:Reliability:

EC0 (24 h) = 6.3 mg/l
EC50 (24 h) = 14 mg/l
EC100 (24 h) = 50 mg/l
all values are nominal(2) valid with restrictions
Test procedure according to national guideline

TEST ORGANISMS- Strain: IRCHA strain- Age: 24 h
DILUTION WATER- Source: synthetic fresh water- Hardness: 2.5 mmol/l Ca + Mg
- Na/K ratio: 10:1
- pH: 8.0 +- 0.2
TEST SYSTEM- Number of replicates: 4- individuals per replicate: 20- Test temperature: 25 +- 1 degrees C(2) valid with restrictions
Test procedure according to national guideline
Critical study for SIDS endpoint(92) (93)07.05.2004

(94)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

staticDaphnia magna (Crustacea)
24 hour(s)mg/l= 12.4noother: AFNOR (1974)1987
no dataother TS: p-cresol, purity > 95 %RemarkResult
Test condition:::

Reliability:

Effect: immobilisation
Result is reported as 24-h IC50 "0.115 mmol/l" (which equals 12.4 mg/l)
Reconstituted hard water, 200 mg/l CaCO3, pH 7.8-8.2
dissolved oxigen >25% of saturation(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail(95) (96)07.05.2004
Type
Species
Exposure period:::

Daphnia magna (Crustacea)
48 hour(s)UNEP PUBLICATIONS233

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Unit
LC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

mg/l
= 1.4
no dataother: according to the method described by Parkhurst et al. 19771979
noother TS: p-cresol, no purity reported

Method:Test condition:

Test substance
Reliability::

Parkhurst BR, Gehrs CW, Rubin IB (1977): Proceedings of ASTM
2nd Annual Symposium on Aquatic Toxicology, 122-130
Daphnia magna used in the test were adults.
100-ml test beakers were filled with 80 ml test solution and
4 daphnia. All the tests were run in triplicate.
Temperature during the test: 25 +/- 0.5°C
12h light/dark cycle
Test solution was prepared with filtered spring water (pH
7.8 alkalinity mg/l, hardness 140 mg/l)
Control beakers were used
48h-EC50 values were obtained by PROBITThe test substance was obtained from an effluent(3) invalid
Methodological deficiencies (method description is in the other reference
from the same author). Age of daphnias used in the test is not clearlyspecified: test daphnias were "adults" (in the OECD guideline a 24h-olddaphnia is suggested); temperature during the test was 25°C (in theguideline is suggested: 18-22°C); 12 daphnia were used for each test
concentration (in the guideline 40 daphnias are suggested)(97)

07.05.2004
Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

staticDaphnia sp. (Crustacea)
48 hour(s)
mg/l
= 12
no

Method:Test condition
Reliability::

test organisms were reared from daphnids collected insurface water
river water, pH 7.5(3) invalid
Experimental details missing. Study does not follow any guideline,
concentrations tested were not reported, no information about theapplication method of the test substance is given. Neither O2/pH
monitoring nor analytical monitoring were applied1959
noother TS: p-cresol, no purity reported

07.05.2004
4.3

TOXICITY TO AQUATIC PLANTS E.G. ALGAE

Species
Endpoint
Exposure period
Unit
Limit test
Analytical monitoring
Method
Year

234

(98)

:
:
:
:
:
:
:
:

Scenedesmus subspicatus (Algae)
other: biomass and growth
48 hour(s)mg/lnoother: DIN 38412, part 91990

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

GLP
Test substance::noother TS: p-cresol, no purity reported

Result:

Test condition:

Reliability:

Flag
07.05.2004:

EbC10 = 2.3 mg/l
ErC10 = 4.6 mg/l
EbC50 = 7.8 mg/l
ErC50 = 21 mg/l
24 +- 1 degrees C; TS concentration 0.8 - 100 mg/l, dilution
series 1:2
preliminary culture 10E5 cells/,lirradiance 17.0 W/m2
(2) valid with restrictions
Test procedure according to national guideline
Critical study for SIDS endpoint

Species
Endpoint
Exposure period
Unit
EC0
EC50
EC100
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Chlorella pyrenoidosa (Algae)
other: chlorophyll content
72 hour(s)
mg/l
< 50
116
250
no
no

Result:

Test condition:

Reliability:

Complete destruction of chlorophyll at 1000 mg/l after 1 day.
EC50 was not reported in the study, but it can be taken from the graph
TEST ORGANISMS- Strain: Emerson strain- Test temperature: 25 +- 1 degrees C- pH: 7.0
- Photoperiod: continuous illumination
TEST PARAMETER: chlorophyll(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
(100)

(99)

12.05.2004

1968
noother TS: p-cresol, no purity reported

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
EC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton coloratus
other: photosynthesis
21 day(s)
mg/l
< .22
= .22
> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 µS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions not indicated. No

no
1983
no
other TS: p-cresol, no purity reported

UNEP PUBLICATIONS

235

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
information about application mode, number of plants, controls, test
concentrations, statistics, analytics.

07.05.2004(101)

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton crispus
other: photosynthesis
21 day(s)mg/l= 1.08> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 µS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions not indicated. No
information about application mode, number of plants, controls, test
concentrations, statistics, analytics.

no
1983
no
other TS: p-cresol, no purity reported

07.05.2004(101)

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
EC50
EC100
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton lucens
other: photosynthesis
21 day(s)
mg/l
< .22
= .22
= .65
> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 µS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions not indicated. No
information about application mode, number of plants, controls, test
concentrations, statistics, analytics.

no
1983
no
other TS: p-cresol, no purity reported

07.05.2004(101)

Species
Endpoint
Exposure period
Unit
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Agmenellum quadruplicatum (Algae)
other: algal lawn assay (growth inhibition)
7 day(s)Method:Algal lawns were initially seeded with 1.0 x 10e+5 cells/ml
in 1% agarized (Difco 0140) medium. The test chemical was

236

no
1978
no
other TS: p-cresol; purity not noted

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

Resultp-CRESOL
ID: 106-44-5
DATE: 24.05.2004:

absorbed onto antibiotic sensitivity disks (12.7 mm;Schleicher and Schuell, No. 740-E) which were placed
directly onto the agar surface. The petri dish cultures weresealed with Scotch Tape and incubated in light from atungsten lamp for 3-7 days at 28-30 degree C. Zone of
inhibition was measured from the edge of the disk in mm.
The radius of growth inhibition around the disk was judged
visually and microscopically.
Concentration (ug/disk)zone of inhibition (mm)
0
0
500
0
1000
8
0 indicates no inhibition,
36 indicates complete inhibition.
No inhibittion was noted with ethanol controls.

Reliability:

LC50 >1000 ug/disk(3) invalid
Unsuitable test system

24.10.2001(102)

Species
Endpoint
Exposure period
Unit
MTL
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Ankistrodesmus falcatus (Algae)
biomass
10 day(s)
mg/l
= 100

Method:RemarkResult::Reliability:

described in: Denson & Bold, The University of Texas,
Publication No. 6022, 72 (1960)
MTL = median tolerance limit
sublethal concentration 100 mg/l
lethal concentration 500 mg/l
(3) invalid
Experimental details missing

no
1976
no
other TS: p-cresol, no purity reported

07.05.2004(103)

Species
Endpoint
Exposure period
Unit
TT
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Scenedesmus quadricauda (Algae)
biomass
96 hour(s)mg/l=6RemarkReliability::

TT = toxicity treshold(3) invalid
Experimental details missingnoother: Cell multiplication inhibition test
1959
noother TS: p-cresol, no purity reported

07.05.2004
Species(98):

other algae: Spirogyra sp.

UNEP PUBLICATIONS

237

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Endpoint
Exposure period
Unit
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other: Photosynthesis and Respiration

MethodResult::Reliability:

Algae exposed in a open channel experimental stream set.
The net oxygen production decreased from 0.084 (control) to
0.022 mg O2/mg DW with 8 mg/l TS. Respiration in the dark
increased from -0.064 (control) to -0.182 O2/mg DW.
(3) invalid
Unsuitable test system

no
1983
no
other TS: p-cresol, purity at least 99 %07.05.2004
4.4

(104)

TOXICITY TO MICROORGANISMS E.G. BACTERIA

TypeSpecies
Exposure period
Unit
IC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
activated sludge of a predominantly domestic sewage
2 hour(s)mg/l= 439.5 calculatednoother: similar to OECD Guideline 209
1999
noother TS: p-cresol, analytical grade

Method:Test condition
Reliability

:
:

Flag
07.05.2004:

O2 measured with an optical scanning respirometer; endpoint:
inhibition of respiration rate
pH 7.0; temp. 20 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
EC75
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
activated sludge of a predominantly domestic sewage

Method:RemarkTest condition
Reliability:::

Quantitative determination of the nitrification rate (1ststep, NH4 to NO2)
colorimetric measurement of the NO2/NO3 concentration;
static test systempre-cleaned activated sludge in particle-free communal waste
water (BOD5: 250 mg/l; NH4-N/l: 50-80 mg)
effect: inhibition of ammonia oxidation
Exposure period: 2-4h; 25 degree C; pH 7.6-7.8(2) valid with restrictions

238

(105)

mg/l
= 16.5noother: inhibition of nitrification process
1966
noother TS: p-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
Study in accordance with generally accepted scientificstandards and described in sufficient detail
Critical study for SIDS endpoint

Flag
07.05.2004:

Type
Species
Exposure period
Unit
IC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Nitrosomonas sp. (Bacteria)
24 hour(s)
mg/l
= 27
No
other: Inhibition of nitrification, comparable to ISO/DIS 9509
1991
No
other TS: p-cresol, no purity reported

MethodRemarkTest condition
Reliability

:
:
:
:

culture obtained from mixed liquor of a treatment plant
Effect: inhibition of N-oxidation
25 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail(106)

07.05.2004

(107)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Tetrahymena pyriformis (Protozoa)
48 hour(s)
mg/l
= 157
No
other: growth inhibition test
1996
Noother TS: p-cresol, purity at least 95 %Test condition
Reliability::

27 +- 1 degrees C; pH 7.35
(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail07.05.2004

(108)

Type
Species
Exposure period
Unit
LC100
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Tetrahymena pyriformis (Protozoa)
24 hour(s)
mg/l
= 400
No

Test condition
Reliability::

28 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail1978
Noother TS: p-cresol, no purity reported

07.05.2004
Type
Species
Exposure period

(109)
:
:
:

Aquatic
Tetrahymena pyriformis (Protozoa)
24 hour(s)UNEP PUBLICATIONS

239

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

mg/l
= 160
No

Method:Reliability:

The test was carried out under sterile conditions. T.
pyriformis was pre-cultured at 30 degree C for 24 hours.
The stock solution of chemical was added to the sterile
medium to provide a constant ratio of 1.8 in 10 ml of 2%
protose peptone. The solutions were then inoculated with
0.2 ml T. pyriformis and cultivated for 24 hours at 30
degree C without agitation. The number of cells werecounted manually under a microscope (repeated 3 times) andwith a Coulter Counter, Model Zb (repeated twice). Meanvalues were recorded with each method. Correlation
coefficient between manual and Couter Counter was 0.998.
(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail1985
no dataother TS: p-cresol; purity analytical grade24.10.2001

(110)

Type
Species
Exposure period
Unit
IC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
other bacteria: Aerobic heterotrophs
49 hour(s)
mg/l
= 260
No

MethodRemark::Test condition
Reliability::

culture obtained from mixed liquor of a treatment plant
Effect: inhibition of respiration; prolonged incubationcompared with ISO 8192
25 and 35 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail

1991
Noother TS: p-cresol, no purity reported

07.05.2004

(107)

Type
Species
Exposure period
Unit
IC50
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

RemarkTest condition
Reliability

:
:
:

240

Aquatic
other bacteria: Methanogenic bacteria
96 hour(s)
mg/l
= 91
No
other: Owen, W.F.: Bioassay for Monitoring Biochemical Methane Potential
and Anaerobic Toxicity. Water Res. 13, 485 (1979)1991
Noother TS: p-cresol, no purity reported
Effect: Inhibition of gas production (CH4 + CO2)
35 degrees C(2) valid with restrictions
Study in accordance with generally accepted scientific

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
standards and described in sufficient detail07.05.2004

(107)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Escherichia coli (Bacteria)

Method:Remark:Reliability:

test organisms isolated from river water
endpoint: inhibition of glucose metabolism
TT = toxicity treshold; determined at 5% effect compared tocontrol(3) invalid
Experimental details missing

mg/l> 1000No
1960
Noother TS: p-cresol, no purity reported

07.05.2004

(111)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Photobacterium phosphoreum (Bacteria)
15 minute(s)
mg/l
= 1.6
No
other: Microtox assay
1987
Noother TS: p-cresol, analytical grade (either from Merck or EGA Chemie)

Remark:Reliability:

Not enough information supplied for assessment of the test used (Testdone according to Beckman manual). Although it is suggested that
Microtox may lack reproducibility due to variations in bacterial cellsuspensions [Bitton G (1983) Bacterial and Biochemical Tests forAssessing Chemical Toxicity in the Aquatic Environment: A Review. Crit
Rev Environ Control 13: 51 -67], no information is supplied on themaintenance of the lyophilized bacteria, their age, duration of reconstitution
and other important parameters.
(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.
(112)

07.05.2004
Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Photobacterium phosphoreum (Bacteria)
30 minute(s)
mg/l
= 1.5
No
other: Microtox assay
1981
no dataother TS: p-cresol, no purity reported

Remark:Test condition
Reliability::

Inhibition of bioluminescence
Secondary literature; not enough information for assessment of cited result
20 degrees C(4) not assignable

UNEP PUBLICATIONS

241OECD SIDS
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ID: 106-44-5
DATE: 24.05.2004
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.

07.05.2004

(113)

Type
Species::

Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Remark:Test condition:

Reliability:

07.05.2004

Aquatic
other bacteria: gentechnologically constructed luminescent bacteria
originating from wastewater treatment plant
30 minute(s)mg/l21 measured/nominalNoother: Microtox assay
1986
no dataother TS: p-cresol, no purity reported
Inhibition of bioluminescence
Modified microorganisms used which represent the metabolic potentials
present in a wastewater treatment plant and some properties of a marineorganism, but which are not identical to any known species in naturalenvironments- Wastewater bacteria (Eschericia coli) which were obtained from awastewater treatment plant- Bacteria obtained the luciferase operon of Vibrio fischeri by transfer fromluminescent E. coli
- Incubation at 20 °C- Result calculated from the difference of the luminescence between
controls and test substance taking into account the light emissions at 0 and
20 °C(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals.
(113)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
Pseudomonas fluorescens (Bacteria)

Remark:Reliability:

TT = toxicity treshold; determined at 5% effect compared tocontrol
endpoint: inhibition of glucose metabolism(3) invalid
Experimental details missing

mg/l
= 30
No
1960
No
other TS: p-cresol, no purity reported

07.05.2004
Type
Species
Exposure period
Unit
EC10
Analytical monitoring
Method
Year
GLP

242

(111)
:
:
:
:
:
:
:
:
:

Aquatic
other bacteria: Photobacterium (Vibrio) fischeri (marine)
5 minute(s)
mg/l
= 1.3
No
other: Microtox assay
1981
No

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test substance:other TS: p-cresol, no purity reported

Remark:Test condition
Reliability::

Although it is suggested that Microtox may lack reproducibility due tovariations in bacterial cell suspensions [Bitton G (1983) Bacterial andBiochemical Tests for Assessing Chemical Toxicity in the Aquatic
Environment: A Review. Crit Rev Environ Control 13: 51 -67], no
information is supplied on the source of the lyophilized bacteria, their age,duration of reconstitution and other important parameters
15 degrees C(3) invalid
Unsuitable test system. Organisms are of marine origin. Method is not
appropriate for the hazard assessment of chemicals(114)

07.05.2004
Type
Species
Exposure period
Unit
IC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
other bacteria: Rhizobium melioti
30 minute(s)mg/l= 7.1 calculatedNo

Remark:Reliability:

endpoint: inhibition of reduction reaction of a dye(3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium
bromide; MTT)
(3) invalid
unusual endpoint

1997
Noother TS: p-cresol, no purity reported

07.05.2004

(115)

Type
Species
Exposure period
Unit
EC0
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Aquatic
other bacteria: Pseudomonas Stamm Berlin 33/2

RemarkReliability::

Effect endpoint: inhibition of cell multiplication(4) not assignable
Experimental details missing

mg/l
= 80
No
1982
No
other TS: p-cresol, no purity reported

12.05.2004
4.5.1

(87)

CHRONIC TOXICITY TO FISH

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
Analytical monitoring
Method
Year
GLP

:
:
:
:
:
:
:
:
:
:

Pimephales promelas (Fish, fresh water)other: growth
32 day(s)
mg/l
1.35
2.57
no dataother: Early life stage test
1984
No

UNEP PUBLICATIONS

243

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test substance:other TS: p-cresol, no purity reported

Test condition:

Reliability:

Flag
07.05.2004:- Delivery system: Flow-through test.
- Dilution water: soft water from lake Superior.
- Fluorescent lights provided 16h light per day.
- Water chemistry data was recorded at the Environmental ResearchLaboratory, Duluth, MN. Recorded data can be required.
- The test was begann with the egg-stage.
- Fish were fed newly hatched brine shrimp ad libitum twice per day so thatmoderate accumulation occured.
- Statistical analysis: effect on growth was examined by log-linear doseresponse analysis; there was a control and five treatments with two
replicates.The lowest effect concentration was determined by Dunnetts
multiple range test. Regression analysis was performed.
- Endpoint: effect on larval growth by measuring lenght or weight(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
water chemistry data not reported
Critical study for SIDS endpoint
(82)

4.5.2

CHRONIC TOXICITY TO AQUATIC INVERTEBRATESSpecies
Endpoint
Exposure period
Unit
NOEC
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Method:Remark:Test condition:

Daphnia magna (Crustacea)
Mortality
21 day(s)
mg/l
1
Yes
other: preliminary guideline proposal of the German Umweltbundesamt,
state 1984-01-01
1988
no dataother TS: p-cresol, no purity reported
Determination of NOEC for reproduction rate, mortality and the time of thefirst appearance of offspring; 21d- Only the ominal value for the most sensitive parameter is given. However
no losses were reported to be greater than 20%.
- Tested concentration range: 0.003-10 mg/l.
- Most sensitive parameter was mortality:
NOEC-nominal value = 1 mg/l
TEST ORGANISMS- Strain: IRCHA strain- Age: 24 h
DILUTION WATER- Source: synthetic fresh water- Hardness: 2.5 mmol/l Ca + Mg
- Na/K ratio: 10:1
- pH: 8.0 +- 0.2
TEST SYSTEM- semistatic system- Number of replicates: 4- individuals per replicate: 20- Test temperature: 25 +- 1 degrees C
H-values and oxygen-concentration were measured during the test in two
tests-vessels per concentration level.The detected variation of theseparameters had no negative influence on the organism.

244

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Reliability:

Flag
07.05.2004:

Species
Endpoint
Exposure period
Unit
NOEC
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

other aquatic worm: Dugesia tigrina
other: mortality, reporduction and
80 day(s)mg/l1Noother: see test conditions
1987
No
other TS: p-cresol, no purity reported

Method:Result:

Test condition
Reliability::

Worms 18-24 days old, length 11-12 mm;
In each flask 10 test organisms (5 each cut into two parts);
regeneration of the lacking parts occurred within 10 days;
the worms were fed in the next 10 days and reached their
original length 20 days after cutting; then animals cut
again, altogether 4 times
LC50 = 11.08 mg/l after 10 days
LC10 = 2.0 mg/l after 80 days (4 generations)
LC20 = 4.0 mg/l after 80 days (4 generations)
20 degrees C; medium according ISO/TC 147/SC 5/GT 3 N. 38(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail(2) valid with restrictions
Study comparable to national guideline
Critical study for SIDS endpoint(92) (93)07.05.2004

(116)

4.6.1

TOXICITY TO SEDIMENT DWELLING ORGANISMS

4.6.2

TOXICITY TO TERRESTRIAL PLANTS

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Raphanus sativus (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:Seeds exposed to test compounds dissolved in distilledwater; 3 replicated of 20 seeds
Concentr. Germination rate% Growth rate%g/l
1 day 4 days Radicle Hypocotyl

Test condition
Reliability

:
:

1989
No
other TS: p-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10
0
0
1
0
0
0.1
70
88.5
65.1
75.6
24 degrees C; 10 h light, 14 h dark(3) invalid
Experimental details missing. No control values for germination reported;
effect values cannot be related to environmentally relevant conditions

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OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

07.05.2004(117)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Brassica rapa (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilledwater; 3 replicated of 20 seeds
Concentr. Germination rate% Growth rate%g/l
1 day 4 days Radicle Hypocotyl

Test condition
Reliability::

07.05.2004

1989
Noother TS: p-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10
0
0
1
0
0
0.1
105.3 100.0
50.9
79.2
24 degrees C; 10 h light, 14 h dark(3) invalid
Experimental details missing. No control values for germination reported;
effect values cannot be related to environmentally relevant conditions(117)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Brassica campestris var. chinensis (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilledwater; 3 replicated of 20 seeds
Concentr. Germination rate% Growth rate%g/l
1 day 4 days Radicle Hypocotyl

1989Noother TS: p-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

:
:

10
0
0
1
0
0
0.1
71.9 103.9
79.4
72.0
24 degrees C; 10 h light, 14 h dark(3) invalid
Experimental details missing. No control values for germination reported;
effect values cannot be related to environmentally relevant conditions(117)

Species
Endpoint
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Lactuca sativa (Dicotyledon)
emergence
3 day(s)mg/l122other: Seed germination test
1978
Noother TS: p-cresol, no purity reported

Method:As described by Reynolds 1975 (Characterization of osmotic restraints on

Test condition
Reliability
07.05.2004

246

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

ResultReliability

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004::

07.05.2004

lettuce fruit germination. Ann. Bot. 39, 791-796) and 1977 (Comparative
effects of aliphatic compounds on inhibition of lettuce fruit germination.
Ann. Bot. 41, 637-648)- Lettuce cultivar Great Lakes- Germination temperature 30 °C
Result was reported as "1.13 mmol/l" which equals 122 mg/l(2) valid with restrictions
Basic data given
(118)

4.6.3

TOXICITY TO SOIL DWELLING ORGANISMS

4.6.4

TOX. TO OTHER NON MAMM. TERR. SPECIESSpecies
Endpoint
Exposure period
Unit
LD50oral
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other avian: Agelaius phoeniceus (red-winged blackbird)
mortality

Test condition:

Reliability:

birds pre-conditioned to captivity for 2 to 6 weeks
dosed by gavage with solution in propylene glycol or bypellets resp. gelatine capsules(2) valid with restrictions
Unsuitable test system

mg/kg bw
= 96
1983
no dataother TS: p-cresol, no purity reported

07.05.2004

(119)

4.7

BIOLOGICAL EFFECTS MONITORING

4.8

BIOTRANSFORMATION AND KINETICS

4.9

ADDITIONAL REMARKS

Memo

:

Sea urchin test

Remark:Test substance:

Reliability:

Strongylocentrotus droebachiensis (sea urchin):static test, 5 degrees C
Determined effect endpoints: death, pathology, inhibition ofcleavage and differentiation, pigment defects
EC50 (96 h): 5 mg/lother TS: p-cresol, purity > 98 % as determined by GC (obtained from
Merck)(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail07.05.2004
Memo

(84)
:

Tree neoplasms

UNEP PUBLICATIONS

247

OECD SIDS
4. ECOTOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Remark:Test substance
Reliability::

p-cresol (1.5% v/v) showed a toxicity rating from 3-4 (0 =no injury, 5 = complete kill within 14d) in tomato crowngall tumors incited by Agrobacterium tumefaciens
other TS: p-cresol, no purity reported(3) invalid
unusual endpoint

07.05.2004

248

(120)

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

5.0

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

TOXICOKINETICS, METABOLISM AND DISTRIBUTIONIn Vitro/in vivo
: In vitroType: Absorption
Species: other: human skin
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle: Water
Route of administration: dermal
Exposure time
: 250 minute(s)Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:nd
2 :3rd:
Toxic behaviour:
Deg. product:
Method: other: see freetext ME
Year: 1977
GLP: no data
Test substance: other TS: p-cresol, purity: reagent grade
Method:Result:Reliability:

Flag
06.02.2004:

The permeability of p-Cresol was measured across 2.5 cm2 epidermal
membranes from human abdominal skin. The membranes were supported
in a glass cell and the amount of p-Cresol passing to the receptor vessel
measured spectrophotometrically. Each test was conducted at least in
duplicate and at 25 Degree Celsius
The permeability coefficient of p-Cresol was 2.92 x10 (exp)-4 cm/min andthe lag time for a 0.4%w/v solution was 16 min. The thresholdconcentration for damage i.e. the aqueous concentration at which thepermeability coefficient began to increase was 8.85 %w/v.
(2) valid with restrictions
in vitro investigation
Critical study for SIDS endpoint(121)

In Vitro/in vivo
: In vivoType: Toxicokinetics
Species: Rabbit
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle: other: sodium hydroxycarbonate
Route of administration: gavage
Exposure time:
Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:

UNEP PUBLICATIONS

249

OECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Toxic behaviour
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:

Method:Result:Reliability:

Flag
06.02.2004:

other: see freetext ME
1949
No
other TS: p-cresol, not specified further
100-200 mg/kg bw was administered to rabbits (number and sex not
mentioned) as single dose as solutions in bicarbonateby gavage. Urine
was collected over a period of 24 -48 hours and the levels of free andconjugated cresol was estimated by the method of Folin O. and Ciocalteu
V., J. biol. Chem. 73, 627 (1927). Metabolites were identified with themethod described in Bray et al., Biochem J. 41, 212 (1947) and 43, 561(1948)
absorption and excretion:
Within 24 hours 65 % of the p-Cresol dose was excreted in the urine
indicating that at least this amount was absorbed through thegastrointestinal tract and urinary excretion was the main route ofelimination.
metabolism:
The principal metabolic pathway was conjugation with glucuronic andsulphuric acids: 15% of the dose were discovered as ethereal sulphate and
61% of the dose as ethereal glucuronide and 2% of the dose as free cresol.
About 7 % of the dose was free hydroxybenzoic acid, about 3 % of thedose was conjugated hydroxybenzoic acid; conjugated dihydroxytoluene
was only discovered in traces as 3,4-dihydroxytoluene.
(2) valid with restrictions
no information on sex and number of rabbits used, no information on
distribution in the tissue
Critical study for SIDS endpoint(122) (123)

In Vitro/in vivo
: In vivo
Type: Distribution
Species: Dog
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle:Route of administration: oral unspecified
Exposure time:
Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:nd
2 :3rd:
Toxic behaviour:
Deg. product:
Method: other: no dataYear
: 1971GLP: No
Test substance: other TS: p-cresol, not specified further
Result:Reliability:

250

Following oral exposure cresols in the body concentrate in the blood, liver,and brain initially, but soon become more widespread and appear in thelungs, kidneys and other unspecified organs (no further details given)(4) not assignable

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Flag
06.02.2004

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004:

secondary literature
Critical study for SIDS endpoint(124)

In Vitro/in vivo
: In vivoType: Absorption
Species: Rat
Number of animals
Males:
Females :
Doses
Males
:
Females : 10 mg/m3
Vehicle: other: airRoute of administration: inhalation
Exposure time
: 4 hour(s)Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:
Toxic behaviour:
Deg. product:
Method: other: female rats,concentr.: 10 mg/m3, 4 hrs daily for 100 d up to 4
monthsYear: 1975
GLP: no data
Test substance: other TS: p-cresol, not specified further
Remark:Reliability:

Flag
06.02.2004:

female rats were exposed to 10 mg/m3 p-cresol 4 hours perday, daily for 100 d up to 4 months. p-Cresol reached aconcentration of 20.7ug/g lung tissue; the neutral red
sorption on day 3 resp d 39 was 150 % resp. 212 % of thecontrol value as a marker for cytotoxicity. Full recovery
did not occur.
(2) valid with restrictions
information on absorption via lung, but study description suffer fromdeficiencies
Critical study for SIDS endpoint(125) (126)

In Vitro/in vivo
: In vivoType: Toxicokinetics
Species: other: dogs and rabbits
Number of animals
Males:
Females :
Doses
Males
:
Females :Vehicle:Route of administration: oral unspecified
Exposure time:
Product type guidance:
Decision on results on acute tox. tests:
Adverse effects on prolonged exposure :Half-lives: 1st:
2nd:
3rd:
Toxic behaviour:

UNEP PUBLICATIONS251

OECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Deg. product:Remark:Reliability
16.01.2003:

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males
Females
Vehicle:::Result:Reliability:

Flag
09.01.2003:

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males
Females
VehicleMethodYear
GLP
Test substance:::In vivo
Excretion
human

:
:

22
10

:
:
:
:
:
:
:

other TS: p-cresol, not specified further

Result:Reliability
Flag
06.02.2004::

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males

:
:
:

In vivo
Excretion
human

:
:

6
4

252

p- Cresol undergoes enterohepatic circulation when administered orally todogs and rabbits.
(2) valid with restrictions(127) (128)
In vivo
Toxicokinetics
other

:
:
:
:
:
At physiological pH, the conjugated metabolites of phenolic compounds are
ionized to a greatedr extent than the parent compound, which reduces therenal reabsorption and increases the elemination with the urine.
In addition to urinary excretion, cresols are excreted in the bile, but themost part undergoes enterohepatic circulation. There are known species
differences in the specific conjugation reactions of cresol isomers. The
relative amounts of glucuronide and sulfate conjugates therefore differ
between species and also vary with the dose.
(2) valid with restrictions
basic information
Critical study for SIDS endpoint(127) (129) (130) (131)

Daily excretion of p-Cresol was measured in the 24-hrs urine samples fromten healthy females and 22 healthy males. Mean urinary p-Cresol levels
were 58.9 +/- 43.7 mg/d for males and 45.7+/-23.5 mg/d for females(2) valid with restrictions
Critical study for SIDS endpoint
(132)

:

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Females
VehicleMethodYear
GLP
Test substance

:
:
:
:
:
:

Result:Reliability
Flag
06.02.2004::

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males
Females
VehicleMethodYear
GLP
Test substance:::

Method:Result:Reliability
Flag
06.02.2004::

In Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males
Females
Vehicle:::In vivo
Metabolism
human

:
:

5
5

Remark:Reliability
Flag
16.01.2003::

other TS: p-cresol, not specified further
Daily excretion rates of p-cresol were measured on 24-hr urine collections
from 4 healthy weman and 6 healthy men ages 21 to 46: women: 59.0
(35.0-75.0) mg/day; men: 46.8 (36.7-56.8) mg/day(2) valid with restrictions
Critical study for SIDS endpoint(133)
In vitro
Metabolism
other: male rat liver slices

:
:
:
:
:
:
:
:
:

other: DMSO

other TS: p-cresol, not specified further
Precision-cut liver slices were prepared from male Sprague-Dawley rats
and incubated in Krebs-Hepes buffer for up to 6 hours. Metabolism studies
were carried out using 1mM concentration of p-cresol for a period of 1 hourand 1 mM glutathione was added. Supernatants from each slice wereanalyzed for glutathione conjugates directly by HPLC.
In slices, p-cresol formed a glutathione conjugate at a rate of 2.31
nmol/h/slice which support evidence of formation of quinone methide asintermediate.
(2) valid with restrictions
Critical study for SIDS endpoint
(134)

:
:
:
Urine was collected from 5 women and 5 men during a period of 24 hours
who were eating self-selected diets. The 24 hours excretions of p-cresol
were 59.7 mg/24 h and 73.9 mg/24 h for males and females, respectively.
(2) valid with restrictions
Critical study for SIDS endpoint(135)

UNEP PUBLICATIONS253

OECD SIDS
5. TOXICITY
5.1.1

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

ACUTE ORAL TOXICITY

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Result:Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
775 - 1000 mg/kg bw
mouse
ICR
male
5
other: corn oil
100 - 1000 mg/kg bw
other: see freetext ME
1989
no dataother TS: p-cresol, purity: 99.8%

Method:Remark:Result:

The test article was administered by oral gavage at a volume
of 5ml/kg. Pre-dosing weight of the animals was 28.0-34.8
grams. Dosing solutions were prepared just prior to dosing.
All animals were examined after dosing and periodicallythroughout the seven day study for toxic effects and/or
mortalities.
Quality Assurance statement signed; Range-finding study formouse dominant lethal assay.
5 minutes of dosing, one animal at 775 mg/kg and one at 1000
mg/kg were exhibiting clonic convulsions and laboredbreathing. All other animals were languid within 5 minutes

254

LD50
= 1800 mg/kg bw
rat
Wistarmale/female
5other: olive oil
1300 - 2700 mg/kg bw
other: 5 rats/sex/dose, administration as a 10% solution in olive oil to nonfasted Wistar rats by gavage to give doses of 1000-2700 mg/kg bw,
observation time was not reported, section was not performed
1944
no dataother TS: p-cresol, purity = 96-98%
Signs and symptoms of poisoning were similar to those causedby phenol which included muscle twitching, temperature andpulse and respiratory rate fluctuations, salivation anduncoordinated leg movements. There was 100% mortality at
2700 mg/kg bw; time of death not mentioned
Dose (mg/kg)
Mortality (%)
1300
20
1500
40
1800
30
2000
50
2200
70
2400
90
2700
100
(2) valid with restrictions
no guideline study: substance given as 10 % solution , description sufferesfrom deficiencies (e.g.: observation time not reported)
Critical study for SIDS endpoint(136)

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
of dosing but resumed normal activity within 10 minutes.
All surviving animals appeared normal and helthy on theeventh day after dosing.
Summary of Mortalities:
Treatment
Observation
100 mg/kg
0/5
325 mg/kg
0/5
550 mg/kg
0/5
775 mg/kg
1/51000 mg/kg
3/5(2) valid with restrictions
dose range finding study
Critical study for SIDS endpoint

Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 1460 mg/kg bw
rat

Remark:Reliability:

p-Cresol was administered as a 10% solution in oil. The
original data are in Russian and no further experimental
details are available from the citing review (IPCS, 1993).
(4) not assignableseondary literature

(137)

other
no dataother TS: purity not noted

06.09.2002(129) (138)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 344 mg/kg bw
mouseRemark:Reliability:

p-Cresol was administered as a 10% solution in oil. The
original data are in Russian and no further experimental
details are available from the citing review (IPCS, 1993).
(4) not assignablesecondary literature

other
1976
no dataother TS: purity not noted

06.01.2003
Type
Value
Species
StrainSex
Number of animals(129) (138)
:
:
:
:
:
:

LD0
= 420 mg/kg bw
rabbitUNEP PUBLICATIONS

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:

Remark:Reliability:

06.01.2003
Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

Flag
06.02.2004

:

5.1.2

no dataother TS: 96-98% pure
p-Cresol was administered as a 20% aqueous emulsion to
non-fasted albino rabbits by stomach tube to give doses of
280-1400 mg/kg bw and the time until death was monitored.
According to the methods section, equal numbers of males and females
were employed and, in the results section, one
animal/dose was tested. Presumably this is one
rabbit/sex/dose but this is unclear in the report. The
total observation period was not reported.
Signs and symptoms of poisoning were similar to thosecaused by phenol which included muscle twitching,temperature and pulse and respiratory rate fluctuations,salivation, convulsions, lethargy and coma. Animals
survived doses of up to 420 mg/kg bw and the times until
death at doses of 620, 940 and 1400 mg/kg bw were 4, 12 and2hr respectively.
(4) not assignable
documentation insufficient for assessment
(136)
LD50
= 207 mg/kg bw
rat
no datamale
5other: none
100, 147, 215, 316 mg/kg bw
other: 5 rats/dose group, 4 doses, undiluted liquid, time of recovery: up to
14 d
1969
no dataother TS: p-cresol, M.P.: 36 C; B.P.: 202 C
Doses and mortality:
100 mg/kg bw: 0/5; 147 mg/kg bw: 0/5; 215 mg/kg bw: 3/5; 316
mg/kg bw: 5/5
Signs of intoxication: hypoactivity, tremors, lacrimation,
dyspnea, hemorrhagic rhinitis, convulsions, prostration,
death
Necropsy of the rats that died revealed gastrointestinal
inflammation and haemorrhage and hyperaemia of the lungs,
liver and kidney.
Survivors showed only gastrointestinal tract inflammation.
(2) valid with restrictions
No information about strain used, GLP
Critical study for SIDS endpoint(139)

ACUTE INHALATION TOXICITY

Type
Value
Species

256

other

:
:
:

LC50
> .71 mg/l
rat

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

StrainSex
Number of animals
VehicleDoses
Exposure time
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:Result:Reliability:

Flag
04.02.2004

:

5.1.3

no datamale
6other: air
1 hour(s)other: 6 rats exposed to 0.71 mg/l for 1 hr, room temperature, up to 14 dpost exposure observation, gross necropsy
1969
noother TS: p-cresol, purity not noted, M.P.:36 C, B.P.: 202 C
Mortality: 0/6; signs of intoxication: none; gross autopsy: no significant
findings(2) valid with restrictions
no guideline study: 1 hr exposure time
Critical study for SIDS endpoint
(139)
other
= .029 mg/l
ratother: aerosol exdosure; no further data
no dataother TS: p-cresol, purity not noted
The mean lethal concentration of p-cresol in rats wasmeasured. The original data are unpublished and no further
experimental details are available from the citing review(IPCS, 1993).
Clinical signs of toxicity included irritation of mucous membranes,
neuromuscular excitiation and convulsions; hematuria at very highconcentrations (no further information)(2) valid with restrictions
Secondary citation from peer-reviewed data source
Critical study for SIDS endpoint(125)

ACUTE DERMAL TOXICITY

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 300 mg/kg bw
rabbitfemale3other: undiluted
130 - 910 mg/kg bw
other: see freetext ME
1977
no dataother TS: p-cresol, not specified further

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Method:Reliability:

Flag
06.02.2004

:

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

LD50
= 750 mg/kg bw
rat

Remark:Reliability:

The dermal LD50 value was measured in rats. No further experimental
details are available from the citing reference (IPCS, 1995).
(4) not assignablesecondary citation(129) (138) (141)13.12.2002
Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Remark:Reliability:

Flag
06.02.2004:

258

The method used was essentially that of Smyth et al. 1962 (Am. Ind. Hyg.
Ass. J. 23, 95-107) except three females/dose were tested 24 hr occlusive
exposure to the neat material was followed by a 14-day observation period.
the most probable LD50 value was determined by the method ofThompson 1947 (Bact. Rev.11, 115-145)of moving averages. Clinical signs
and purity of the Ts are not reported.
(2) valid with restrictions
no guideline study: clinical signs and purity of Ts are not reported
Critical study for SIDS endpoint
(140)

other
no dataother TS: p-cresol, purity not noted

LD50
ca. 300 mg/kg bw
rabbitno datano data5other: noneother: 5 rabbits/dose, 4 doses, exposure time not mentioned, up to 14 dobservation time, gross autopsy
1969
noother TS: p-cresol, purity not noted; M.P.: 36 C; B.P.: 202 C
doses and mortality:
215mg/kg bw: 1/5; 316 mg/kg bw: 3/5; 464 mg/Kg bw: 4/5; 681
mg/kg bw: 5/5
signs of intoxication from 4-12 hrs post appl.: tremor,
salivation sedation, deathdermal irritation: severe subdermal hemorrhaging, severe
erythemagross autopsy: survivors: no significant findings;
decedents:
inflammation of kidneys(2) valid with restrictions
no information about strain used and no information on GLP
Critical study for SIDS endpoint(139)

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY
5.1.4

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

ACUTE TOXICITY, OTHER ROUTES

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:other= 110 mg/kg bw
mouse

i.p.
other
no datano datap-Cresol, dissolved in 0.9% saline, was administered toanaesthetized albino Sheffield mice by intraperitoneal
injection. The dose inducing convulsions in 50% of themice (CD50) was measured; the endpoint being taken as
myoclonic jerks of limbs and tails.
The intraperitoneal dose inducing convulsions in 50% of agroup of six male mice (CD50) was 1.02 (95% CI 0.68-1.54)
mM/kg bw (110 (95% CI 74-167) mg/kg bw).

22.03.2001

(142)

Type
Value
Species
StrainSex
Number of animals
VehicleDoses
Route of admin.
Exposure time
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:LC50= 150 mg/kg bw
mouse

s.c.
other
no datano data
Mice received a single subcutaneous injection of p-cresol.
No further experimental details are available in the citingreference (Sternitzke et al. 1992).

22.03.2001
5.2.1(143) (144)

SKIN IRRITATION

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
Method

:
:
:
:
:
:
:
:
:
:

rabbitundiluted
Semiocclusive
4 hour(s)6corrosiveother: see freetext ME

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Year
GLP
Test substance

:
:
:

1977
no dataother TS: p-cresol, not specified further

Method:Reliability:

Flag
06.02.2004:

TS applied to the clipped backs or flanks of the rabbits (no data whether
the test substance was moistened). The material was covered by a surgicalgauze two layers thick, gauze patches were held in place with strips of
Elastoplast tape for 4 hours. After 4 hrs the patches were carefully
removed and the test areas were evaluated for visible tissue destruction.
evaluation criterias:
When visible tissue destruction occurred in at least 2/6 rabbits, the test
materials were classified as corrosive (no further details given).
(2) valid with restrictions
description of the method suffers from deficiencies
Critical study for SIDS endpoint(140)

Species
Concentration
Exposure
Exposure time
Number of animals
VehiclePDII
ResultClassification
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability:

Flag
06.02.2004

:

5.2.2

highly irritatingother: 0.5 ml undiluted TS was applied to the intact and abraded skin, timeof observation: 24 and 72 hrs.
1969
no dataother TS: p-cresol, M.P.: 36 C; B.P.: 202 C
intact skin: erythema: 24 hr: Score 4 in 6/6
72 hr: Score 4 in 6/6
edema: 24 hr: Score 4 in 6/6
72 hr: Score 4 in 6/6
abraded skin: erythema: 24 hr: Score 4 in 6/6
72 hr: Score 4 in 6/6
edema: 24 hr: Score 4 in 6/6
72 hr: Score 4 in 6/6
no tissue destruction and /or necrosis reported
Summary: irritation score: 8.00/8.00(2) valid with restrictions
limited documentation; no information on exposure time
Critical study for SIDS endpoint(139)

EYE IRRITATION

Species
Concentration
Dose
Exposure time
Comment
Number of animals
VehicleResultClassification
Method260

rabbitundiluted
no datano data
6

:
:
:
:
:
:
:
:
:
:

highly irritating
other

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Year
GLP
Test substance:::

Remark:Reliability:

13.12.2002
Species
Concentration
Dose
Exposure time
Comment
Number of animals
VehicleResultClassification
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:Reliability:

Flag
06.02.2004:

5.3

no datano data
The individual cresol isomers cause severe irritation whenapplied directly to the cornea. Mice exposed to highatmospheric concentrations of "cresylic acid vapours"
suffered eye irritation. The original data for the former
effect are unpublished and available from the US EPA
Freedom of Information Office. No further details areavailable in the citing reviews. The latter findings werereported in a 1941 study using Shell cresylic acids;
apparently not cresols themselves (Campbell, 1941).
(4) not assignable
Review(145) (146) (147) (129)rabbitundiluted.1 ml
unspecified
6
highly irritatingother: 0.1 ml undiluted TS, time of reading: 24, 48, 72 hrs
1969
no dataother TS: p-cresol, M.P.: 36 C, B.P.: 202 C
24 hours: cornea, iris, conjunctivae: 84.7/110 (mean score)mean score for cornea: 60; mean score for iris: 10; mean score for
conjunctivae: 14.7)
48 hours: cornea, iris, conjunctivae: 89.7/110 (mean score)mean score for cornea: 63.3, mean score for iris: 10, mean score for
conjunctivae: 16.3)
72 hours: cornea, iris, conjunctivae: 93.0/110 (mean score)mean score for cornea: 66.6, mean score for iris: 10; mean score for
conjunctivae: 16.3)
summary: irritation score: 93.0/110(2) valid with restrictions
no information on GLP, strain used
Critical study for SIDS endpoint(139)

SENSITIZATION

Type
SpeciesNumber of animals
VehicleResultClassification
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

other: maximization test
human

Method:A maximization test was conducted on 25 volunteers using apetrolatum
not sensitizing
other: see freetext ME
1966
no dataother TS: p-cresol, purity not noted

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

ResultReliability

:
:

Flag
08.01.2003:

Type
Species
Concentration:::

Number of animals
VehicleResultClassification
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Reliability:

Flag
06.02.2004:

5.4

other: modified Draize test
guinea pig
1st: Induction .1 % intracutaneous
2nd: Challenge 10 % intracutaneous
3rd: Challenge 10 % other: topical application
10
no data
not sensitizing
other: see freetext ME
1978
no dataother TS: p-cresol, not specified further
10 guinea pigs (4 males and 6 females or vice versa). Both flanks of eachguinea pig were shaved, intradermal injections or topical applications were
performed without occlusion.
Primary irritation tests were performed to determine the suitableconcentrations.
METHOD:
Each animal was injected intradermally with 0.1 ml of TS at 2.5 times thedetermined injection challenge concentration (ICC) of 0.1 % at 4 sites
which overlie the 2 auxilliary and the 2 inguinal lymph nodes. 14 days later
each animal was challenged intradermally in one flank and topically in theother with 0.1 ml aliquots of TS at the respective ICC and application
challenge concentration (ACC; 10%). 24 hours later the reactions werescored. To confirm the result, the procedure was repeated including a
confirmatory challenge with controls.
(2) valid with restrictions
small number of animals tested; reactions should have been scoredadditionally at 48 hours
Critical study for SIDS endpoint(149)

REPEATED DOSE TOXICITY

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group262

4% concentration of p-cresol in petrolatum. The
maximization test involves an induction phase of fiveconsecutive 48-hr covered patch tests, sometimes separated
by 24-hr periods of treatment with a mild irritant,followed 10-14 days later by a 48-hr challenge patch using
the same concentration (see: Kligman AM (1966) The identification ofcontact allergens by human assay. III. The maximization test. A procedure
for screening and rating contact sensitizers, J. invest. Derm. 47, 393)
There were no sensitization reactions in any of the volunteers.
(2) valid with restrictions
cited in monograph of a peer-reviewed international journal;
Critical study for SIDS endpoint
(148)

:
:
:
:
:
:
:
:
:
:

Sub-acuteratmale/female
other: Fischer 344/N
oral feed
28 dayscontinuously in dietnone
0, 300, 1000, 3000, 10000, 30000 ppm (see freetext RM)
yes, concurrent no treatment

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:

1000 ppm
other: see freetext ME1991
yesother TS: p-cresol, purity > 98%

Method:SIZE OF STUDY GROUP:
5 male and 5 female rat per group
TIME HELD BEFORE STUDY: 13-15 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into groups per sex
DIET: NIH-07 rat ration
ANIMAL ROOM ENVIRONMENT:
temperature: 72° +/-3° F, humidity: 50 % +/-15 %, Fluorescent light: 12
hrs/day, room air changes : 10-12 changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly, and at termination,
feed consumption by cage recorded twice weekly
NECROPSY AND HISTOLOGIC EXAMINATION:
necropsy and tissue collection performed for all animals. A complete
histopathologic examination was conducted on all control animals, allanimals in the highest dose group with at least 60 % survivors at study
termination, and all aninmals in higher dose groups inclusive of early
deaths. The following organs and/or tissues were included in complete
histopathological examinations, as well as any tissue masses, grosslesions, and associated regional lymph nodes: adrenals, aorta, bone(sternebrae, femur, or vertebrae, including marrow), brain, bronchi, clitoral
gland, epididymis, oesophagus, heart, kidney, large intestines (caecum,colon, rectum), liver, lungs, lymph nodes (mesenteric), mammary glands,
nasal cavity and turbinates, oral cavity, ovaries, pancreas, parathyroids,
pharynx, pituirary, preputial gland, prostate, salivary glands, scrotal sac,seminal vesicles, skin, small intestine (duodenum, ileum, jejunum), spleen,
stomach, testes, thymus, thyroid, tongue, trachea, tunica vaginalis, urinary
bladder, uterus and Zymbal's glands. Target organs and gross lesions
were examined at lower doses until a no-observed chemical effect wasdetermined. Target organs included the following: nasal epithelium, bonemarrow, uterus, liver, kidney. Organ weights recorded for brain, liver, rightkidney, thymus, heart, and lungs of all animals, and the right testis of all
males.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test

Remark:Result:mean compound consumption (mg/kg bw/day):males
females0 ppm
00300 ppm
25
251000 ppm
8783
3000 ppm
256242
10000 ppm
835
769
30000 ppm
2180
2060
There were no deaths.
30000 ppm: Decreased mean final body weights, body weight gains andfeed consumption occurred in both the
top-dose males and females. These animals also showedclinical signs of toxicity, including hunched posture andrough hair coat (individual animal data not given).
At study termination, weights (w) were sign. increased:
liver (male, rel. w from 10000 ppm, p</=0.01; female: rel w from 3000 ppm,p</=0.05); kidney (male, rel. w from 10000 ppm, p</=0.05; female, rel. w.
at 30000 ppm p</=0.01); brain (male, rel. and abs. w at 30000 ppm

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OECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
p</=0.05; female, rel. w at 30000 ppm, p</=0.05); male right testis (rel. w at
30000 ppm, p</=0.05) (individual animal data not given)
No gross lesions were noted at necropsy. No microscopic changes werereported from brain, liver and kidneys.
Histopathological evaluation, characterized by avarage severity scorebased on a scale of 1 to 4 (1=minimal, 2=mild, 3=moderate, 4=marked),
revealed effects:
female uterus (moderate atrophy at 30000 ppm: 3/5); in the nasal cavity,
nose: atrophy of olfactory epithelium, at 30000 ppm, male: 5/5, female: 4/5,
mild; respiratory epithelium hyperplasia, , from 3000 ppm, male: 1/5,
4/5,5/5, female: 1/5, 3/5, 3/5, minimal to moderate; respiratory epitheliumsquamous metaplasia, male: 2/5, at 30000 ppm, mild, female: 1/5 at 10000
ppm, mild), bone marrow (hypocellularity: male, from 3000 ppm: 1/5, 1/5,
5/5, mild to moderate; female, from 10000 ppm: 1/5, 3/5 mild to moderate)
local toxicity:
NOAEL(male, female): 1000 ppm
systemic toxicity: NOAEL(male, female): 1000 ppm(1) valid without restriction
Critical study for SIDS endpoint

Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Sub-acutemouse
male/female
B6C3F1oral feed
28 dayscontinuously in dietnone
0, 300, 1000, 3000, 10000, 30000 ppm (see freetext RM)
yes, concurrent no treatment
1000 ppm
other: see freetext ME1991
yesother TS: p-cresol, purity > 98%

Method:SIZE OF STUDY GROUP:
5 male and 5 female mice per group
TIME HELD BEFORE STUDY: 13-15 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into groups per sex
DIET: NIH-07 mouse ration
ANIMAL ROOM ENVIRONMENT:
temperature: 72° +/-3° F, humidity: 50 % +/-15 %, Fluorescent light: 12
hrs/day, room air changes : 10-12 changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly, and at termination,
feed consumption by cage recorded twice weekly
NECROPSY AND HISTOLOGIC EXAMINATION:
necropsy and tissue collection performed for all animals. A complete
histopathologic examination was conducted on all control animals, allanimals in the highest dose group with at least 60 % survivors at study
termination, and all aninmals in higher dose groups inclusive of early
deaths. The following organs and/or tissues were included in complete
histopathological examinations, as well as any tissue masses, grosslesions, and associated regional lymph nodes: adrenals, aorta, bone

264

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5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(sternebrae, femur, or vertebrae, including marrow), brain, bronchi, clitoral
gland, epididymis, oesophagus, gallbladder, heart, kidney, large intestines(caecum, colon, rectum), liver, lungs, lymph nodes (mesenteric), mammary
glands, nasal cavity and turbinates, oral cavity, ovaries, pancreas,parathyroids, pharynx, pituirary, preputial gland, prostate, salivary glands,
scrotal sac, seminal vesicles, skin, small intestine (duodenum, ileum,jejunum), spleen, stomach, testes, thymus, thyroid, tongue, trachea, tunica
vaginalis, urinary bladder, uterus and Zymbal's glands. Target organs andgross lesions were examined at lower doses until a no-observed chemical
effect was determined. Target organs included the following: nasal
epithelium, bone marrow, liver, kidney and lymphoid organs. Organ weights
recorded for brain, liver, right kidney, thymus, heart, and lungs of all
animals, and the right testis of all males.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test

RemarkResult::mean compound consumption (mg/kg bw/day):males
females0 ppm
00300 ppm
50
601000 ppm
163
207
3000 ppm
469
564
10000 ppm
1410
1590
Consumption data for the top dose were notcalculated due to 100% mortality at this level.
30000 ppm: all mice died: 5 male and 5 female mice
10000 ppm: 1/5 male died, mean final body weights and mean body weightgains for surviving males were significantly
lower than in the control groups; male and female: feed consumption wasdepressed at the beginning of the study (individual animal data not given)
Clinical signs of toxicity
included hunched posture, rough hair coat, lethargy, and hypothermia in
the top-dose females that died and, together with laboured breathing andpaleness, in the males fed >/= 10000 ppm (individual animal data notgiven)At study termination weights (w) were sign. increased:heart (male, rel. w at 10000 ppm, p</=0.01), right kidney (male, rel. w from3000 ppm, p</=0.05), liver (male, rel. w at 10000 ppm, p</=0.01; female,rel. w from 3000 ppm, p</=0.05 and abs. w at 10000 ppm,p</=0.01)(individual animal data not given)
No gross lesions were noted at necropsy.
Histopathological evaluation, characterized by average severity scorebased on a scale of 1 to 4 (1=minimal, 2=mild, 3=moderate, 4=marked),
revealed effects:
bone marrow hypocellularity (at 30000 ppm, 5/5 male, 4/5 female, mild),
renal tubule necrosis (at 30000 ppm: 4/5 male, 3/5 female, mild), liver:centrilobular atrophy: at 30000 ppm, male 1/5, moderate; centrilobular
necrosis, at 30000 ppm, 1/5 male, 1/5 female, mild; necrosis,at 30000 ppm,
2/5 male, moderate), nose: olfactorium epithelium (o.e.) atrophy, 1/5 maleat 30000 ppm; mild hyperplasia, from 1000 ppm, male 1/5, 1/5, minimal tomild; o.e. necrosis, at 30000 ppm, 2/5 male, 3/5 female, mild; o.e.
squamous metaplasia, from 10000 pp, 1/5, 1/5 male, mild to moderate;
respiratory epithelium (r.e.) hyperplasia, from 1000 ppm, male, 3/5, 5/5,
5/5, 1/5, minimal to mild, female, from 300 ppm, 1/5, 2/5, 4/5, 5/5, 1/5,
minimal (minimal effect without dose response relationship, only infemales); r.e. atrophy at 30000 ppm, male,1/5, mild; r.e. squamous
metaplasia, 2/5 male, at 10000 ppm, mild)
local toxicity: NOAEL(male): 300 ppm
NOAEL(female): < 300 ppm

UNEP PUBLICATIONS265

OECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
systemic toxicity: NOAEL(male, female): 1000 ppm(1) valid without restriction
Critical study for SIDS endpoint

Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Sub-chronicratmale/female
Sprague-Dawley
gavage13 weeks
7 days/week
no0, 50, 175, 600 mg/kg bw/day dissolved in corn oil
yes, concurrent vehicle
50 mg/kg bw
other: see freetext ME
1986
yesother TS: p-cresol, purity: 99.9 %Method:Result:30 rats/sex/dose,
additional 10 rats/sex/dose for baseline clinical pathology
interim kill at week 7
bws were recorded on test day1 and weekly thereafter; individual foodconsumption data were collected weekly;
moribund/mortality check twice daily (moribund rats were killed andnecropsied); physical examination weekly; ophthalmologic examination
during quarantine period and in test week 13
HAEMATOLOGY
haemoglobin, haematocrit, prothrombine time (PT), erythrocyte count,reticulocyte count, total and differential leucocyte count, activated partial
thromboplastin time (APTT)
CLINICAL CHEMISTRY
sodium, chloride, potassium. direct and total bilirubin, alkaline
phosphatase, total cholesterol, albumin, CO2, SGPT, SGOT, glucose,
BUN, globulin (calculated), total protein, creatinine, Albumin/Globulin ratio(calculated
URINALYSIS
appearance, volume, colour, specific gravity, pH, protein, glucose, ketone,
bilirubin, urobilinogen, haemoglobin, microscopic examination
PATHOLOGY
determination of weights of:heart, liver, spleen, brain, kidneys, gonads, adrenals, thyroid/parathyroid
examination of all control rats and high dose rats at study termination as
well as those that died during the study:
all gross lesions,brain (3 levels), spleen, bone (with marrow), skeletal muscles, salivary
gland. mammary gland, thymus, thyroid (with parathyroid), lungs (withmainstem bronchi), trachea, liver, urinary bladder, testes, prostate, ovaries,
corpus and cervix uteri, eye, pituitary gland, lymph node, spinal cord, heart,
aorta, siatic nerve, pancreas, oesophagus, kidneys, small and large
intestine, adrenals, stomach
STATISTICAL ANALYSIS
One-way Analysis of Variance tests with Dunnett's t-test
600 mg/kg: 3 females died within the first 3 days of dosing. Overt signs of
toxicity at this dose included lethargy, tremors, convulsions and coma.
BODY WEIGHT was sign. reduced (p</=0.05):
50 mg/kg bw: female, at week 1, 2, 3, 4, 5, and 7
175 mg/kg bw: male, at week 2, 3, and 4
600 mg/kg bw: male, except week 1 in all weeks; female, week 2, 3, 4, 5, 6,

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ID: 106-44-5
DATE: 24.05.2004

Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period

:
:
:
:
:
:

7, 8, 9, and 14
BODY WEIGHT GAIN was sign. reduced (p</=0.05):
50 mg/kg bw: female, week 2, and 3
175 mg/kg bw: male, week 1, 2, and 3; female, week 1 and 2
600 mg/kg bw: male, all weeks; female, week 1, 2, 3, 4, 5, 6, 7, 10, 13
FOOD CONSUMPTION data was sign. reduced (p</=0.05):
50 mg/kg bw: male, week 5, 9; female, week 1 and 2
175 mg/kg bw: male, week 1, and 5
600 mg/kg bw: male, week 1, 2, 3, 4, 5, 6, 7, and 9; female, week1, 2, and5
CLINICAL PATHOLOGY, only sign. changes (p</=0.05):
Male:
APTT, 600 mg/kg bw, increased; total protein from 175 mg/kg bw
increased; Ca, at 175 mg/kg bw increased; phosphate, 600 mg/kg bw,
increased
Female:
RBC, HGB, HCT, from 175 mg/kg bw, decreased; CO2, at 175 mg/kg bw,
decreased; SGPT, SGOT, Cholesterin, at 600 mg/kg bw increased;
OPHTHALMOLOGY:
Treatment related changes were not seen.
ORGAN WEIGHTS (rel. and abs., only sign. changes, p</=0.05):
Male:
Heart, rel., at 600 mg/kg bw increased; liver, 600 mg/kg bw, abs. decrease,rel. increase; spleen, 600 mg/kg bw, absol. decreases; right and left kidney,from 175 mg/kg bw, rel. increased; right and left testis, at 600 mg/kg bw,
rel. increased; brain, at 600 mg/kg bw, abs. decreased, rel. increased;
Female:spleen, at 50 mg/kg bw, rel. increased (no histopathologic correlate); rightkidney, at 600 mg/kg bw, rel. increased; right ovary, at 600 mg/kg bw,
ovary and brain, abs. decreased
PATHOLOGY:
Gross necropsy examinations did not detect treatment- related changes.
Histological examination:
male:chronic nephropathy in all rats including controls:a slight increased incidence in all dosed males when compared to thecontrols. The increased incidence was significantly greater (p</=0.05) atthe low and the high dose but not at the middle dose. The proportion of rats
with minimal and mild nephropathy was generally similar for all male rats
including controls:
controls: 4/20 = 20%, severity(s): minimal 3/4, mild 1/4;
50 mg-gr.: 11/20 = 55%, s: minimal: 3/11, mild: 2/11
175 mg-gr.: 7/20 = 35%, s: minimal: 7/7, mild:0/7
600 mg-gr.: 12/20 = 60%, s: minimal: 9/12, mild: 3/12
(no dose-response relationship, controls also affected, no increase inpercentage of severity in dosed rats when compared to the controls)male, female:epithelial metaplasia of the trachea:sign, at 600 mg/kg bw (p</=0.05), 10/20 males, 9/19 females
The incidence of this lesions was similiar for low dose, mid dose andcontrol(1) valid without restriction
Critical study for SIDS endpoint
(151)
rat
femaleno datainhalation
4 months

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OECD SIDS
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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Frequency of treatm.
Post exposure period
Doses
Control group
LOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

daily
2 months
0.01 mg/l
no data specified= .01 mg/lotherRemark:Result:Reliability:

Females were exposed to p-cresol aerosols. The original
data are unpublished and no further experimental details
are available from the citing review (IPCS, 1993).
Clinical signs of toxicity included loss of appetite, marked
emaciation and decreased locomotor activity. Irritative
effects, which persisted throughout recovery, were seen on
the nose, eye and skin. Decreased body weight gain and lungweight, increased liver weight, oliguria and dystrophic
changes in the lung and liver occurred. Throughout recovery
the body weights remained depressed and urinary excretion
remained low.
(4) not assignablesecondary literature: experimental details are missing, only one dose used(125)

15.10.2002
Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
LOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Remark:Result:Reliability:

15.10.2002
Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.

268

:
:
:
:
:
:
:

no dataother TS: p-cresol, purity not notedmouse
femaleCBAdermal6 weeks
3x/week
6 months
0 or 0.5 % in acetone
yes, concurrent vehicle< .5 %<= .5 %
other: see freetext RM
1974
no dataother TS: p-cresol, purity not noted
p-Cresol was applied to the skin of five female Agouti mice.
Hair colour was observed weekly for the subsequent 6 months.
Microscopic examinations of post-treatment hairs and skinbiopsies of areas of non-pigmented and normally pigmented
hair were made. Control groups of animals received acetone.
Topical application caused hair depigmentation. No
microscopic changes were noted.
(3) invalid
special study and only one dose used, no dose-response relationship canbe derived and thus no NOAEL or LOAEL can be deduced.
(152)
mouse
male
C57BL
dermal6 weeks
3x/week

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Post exposure period
Doses
Control group
NOAEL
LOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

6 months
0.5 % in acetone
no data specified< .5 %<= .5 %
other: see freetext RM
1974
no dataother TS: p-cresol, purity not noted

Remark:Result:Reliability:

p-Cresol was applied to the skin of 30 males. Hair colour
was observed weekly for the subsequent 6 months.
Microscopic examinations of post-treatment hairs and skinbiopsies of areas of non-pigmented and normally pigmented
hair were made. Control groups of animals received
acetone.
Topical application caused depigmentation of the hair andpigmented epidermis, especially of the tail. Large amountsof p-cresol were lethal and had a local caustic, erosive
effect.
(3) invalid
special study and only one dose used, no dose-response relationship canbe derived and thus no NOAEL or LOAEL can be deduced.
(152)

15.10.2002
5.5

GENETIC TOXICITY ‘IN VITRO‘

Type
System of testing
Test concentration
Cycotoxic concentr.

:
:
:
:

Metabolic activation
Result
Method

:
:
:

Year
GLP
Test substance:::

Method:ResultReliability

:
:

Flag
06.02.2004:

Type
System of testing::

Ames test
Salmonella typhimurium TA 98, TA100, TA1535, TA1537.
0.0, 3.3, 10.0, 33.0, 100.0, 333.0 ug/plate in water as solvent
to select dose range the chemical was checked for toxicity to S. typh.
TA100with and without
negative
other: preincubation methodology according to Ames, Mutat. Res. 31, 347(1975) and Yahagi, Cancer Lett. 1, 91 (1975);
1983
no dataother TS: p-cresol, purity >97%
S-9 FRACTION: liver fractions were prepared from male Sprague-Dawley
rats and male Syrian hamsters that were injected with Arcolor 1254;
POSITIVE CONTROLS: 2-aminoanthracene, 4-nitro-o-phenylenediamine,
sodium acide 9-aminoacridine;
SOLVENT: water,
POSITIVE RESPONSE: was indicated by a reproducable, dose-related
increase wether it be two-fold over background or not
STATISTICAL METHODS: analysis based on the models presented by
Margolin
Positive controls were functional(2) valid with restrictions
only 4 strains of Salmonella typhimurium were used
Critical study for SIDS endpoint(153)
Cytogenetic assay
Chinese hamster ovary cells

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OECD SIDS
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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Test concentration:

treatment time: 20 hrs:
-S9-mix, 100, 150, 200, 301 ug/ml performed twice; +S9-mix: 301, 601,
902 ug/ml;
treatment time: 10 hrs:
+S9-mix: 150, 225, 300 ug/ml performed twice

Cycotoxic concentr.

:

Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:

Preliminary range-finding assays were performed (3.01-3010 µg/ml) to
determine cytotoxicity: -S9-mix: >=301 µg/ml; +S9-mix: >=100µg/ml
with and without
positive
OECD Guide-line 473
1987
yesother TS: p-cresol, 99.8% pure

Method:Result:Reliability
Flag
06.02.2004

:
:

Type
System of testing
Test concentration:::

Cycotoxic concentr.
Metabolic activation
Result
Method

:
:
:
:

Year
GLP
Test substance:::

Method:270

Duplicate CHO cultures were incubated for 20 hrs with 100-301 ug/ml of
the test substance in the nonactivation aberrations assay.
The metabolic activation cultures were treated with 100-300
ug/ml of the test substance in a 10 hour assay and with
301-902 ug/ml in a 20 hour assay.
Solvent: DMSO
positive control: Mitomycin C, cyclophosphamide
statistical evaluation: Fisher's Exact Test with an adjustment for multiple
comparisonsnonactivation assay and incubation for 20 hrs:
Increases in chromosomally aberrant cells ranging between 6.5 % and 11% cells with aberrations (versus 1.0% of solvent control) or between 4%
and 14 %.cells with aberrations (versus 2.0 % of solvent control),respectively.
Positive control was functional in each trial
Incubation for 20 hours with metabolic activation:
Increases in the chromosomally aberrant cells ranging between 18 % and40.5 % cells with aberrations(902 µg/ml was toxic, versus 1.5% of solvent
control) and between 17 % and 43 % cells with aberrations (902 µg/ml was
toxic, versus 3.0 % of solvent control), respectivly.
Posivive control was functional in each trial .
Incubation for 10 hours in the presence of S9-mix:no significant difference
to the solvent controls; positive controls were functional(1) valid without restriction
Critical study for SIDS endpoint(154)
Mouse lymphoma assay
L5178Y TK+/- mouse lymphoma cellswith activation: 0.256 ug/ml, 0.511 ug/ml, 0.767 ug/ml, 1.02 ug/ml, 1.53
ug/ml, and 3.07 ug/ml. without activation: 51.1 ug/ml, 102 ug/ml, 153
ug/ml, 204 ug/ml, 307 ug/l, and 409 ug/ml.
with activation: 7.98 ug/ml. without activation: 511 ug/ml.
with and without
negative
other: similar to OECD Guide-line 476, No differentiation between large
and small colony mutants see also freetext ME
1988
yesother TS: p-cresol, 99.8% pure
S9-MIX: of rat liver was used as metabolic activation system
SOLVENT: DMSO,POSITIVE CONTROLS: ethylmethane sulfonate, 3-methylcholantrene,
POSITIVE RESPONSE was indicated by a >= two-fold increase over the
concurrent background frequency

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Result:Reliability:

Flag
06.02.2004:

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

DNA damage and repair assay
human lymphocytes
5 - 25 uM
no datawithout
positive
other: see freetext ME
1986
no dataother TS: p-cresol, not specified further

Method:Result:Reliability:

Flag
06.02.2004:

p-Cresol was tested for its ability to inhibit
semiconservative DNA synthesis. Initially, DNA repair was
induced by irradiation and, in these cells, semiconservative
DNA synthesis was blocked by treatment with hydroxyurea. In bothstudies, cells were treated withradiolabelled thymidine for 2 hours and incorporation ofthymidine into the cells was measured.
no solvent mentioned, no negative or positive control, no statisticalevaluation reported
p-Cresol inhibited both UV-induced DNA repair synthesis andsemiconservative DNA synthesis as seen by a reduction inradiolabelled thymidine incorporation. It was unclear fromthe report if this inhibition was seen at all concentrations
tested but at the top dose, 21% inhibition of DNA repair
synthesis and 25% inhibition of semiconservative DNA
synthesis was found.
(2) valid with restrictions
no solvent mentioned, no negative or positive control, no information on
cytotoxicity, no statistical evaluation reported
Critical study for SIDS endpoint
(156)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Sister chromatid exchange assay
human lymohocytes
0 - 0.5 mM
no datano datanegative
other: see freetext ME
1986
no dataother TS: p-cresol, 99.9% purity

Method:Remark:Reliability:

Lymphocyte fraction from healthy donors were grown in Medium 199 with
Earles salts. After 24 hrs of cultur p-Cresol diluted in DMSO was added for
88-90 hrs.
positive control: Styrene-7,8-oxide.
statistical method: Linear regression analysis
Results of the positive control or solvent control in comparison to p-cresol
are not given(2) valid with restrictions

The positive controls were functional.
p-Cresol was evaluated as non-mutagenic in the mouse lymphoma cellsystem(2) valid with restrictions
No differentiation between large and small colony mutants;
statistical evaluation not mentioned
Critical study for SIDS endpoint(155)

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
Study description suffers from deficiencies: no information aboutcytotoxicity and whether a metabolic activation system was used or not,only summary results given
Critical study for SIDS endpoint
(157)

Flag
06.02.2004:

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Ames test
Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538
0, 0.5, 5, 50, 500, 5000 ug/plate dissolved in DMSO, highest dose cytotoxic
5000 ug/platewith and without
negative
other: see freetext ME
1975
no dataother TS: p-cresol, purity : 98 %Method:RemarkReliability
Flag
06.02.2004:::

plate incorporation. method according to Ames, Mutat. Res. 31, 347(1975), solv.: DMSO, S9-MIX: of Aroclor-pretreated rat liver as metabolic
activation. system
CONTROLS: as positive control:sodium azide,2-nitrofluorene, 9aminoacridine,2-aminoanthracene,
as solvent control: DMSODATA EVALUATION: Significance level for positive dose-response effects
were obtained with the Joncheere test
STATISTICAL ANALYSIS: Joncheere test
Positive controls were functional(1) valid without restriction
Critical study for SIDS endpoint
(158)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Sister chromatid exchange assay
cultured male human fibroblasts
0, 0.008, 0.8, 4, 8 mM diluted in 95 % EtOH, 10, 30 mM diluted in MEM
from 10 mM onwards
without
negative
other: see freetext ME
1984
no dataother TS: p-cresol, > 99% pure

Method:Remark:Reliability:

p-Cresol was added to the cells and incubated, in
triplicate, at 37 C for 2 hours. Following exposure, the cells were washed,reincubated in the absence of the test chemical for 48 hours, harvested
and SCE frequency and cell-cycle kinetics analysed.
SOLVENT: p-Cresol was dissolved in
95% ethanol at concentrations up to and including 8 mM andin Eagle's minimum essential medium (MEM) at concentrations above this.
CONTROLS: 95% Ethanol and mitomycin C were used as negative andpositive controls respectively.
EVALUATION CRITERIA: positive if a dose-dependant significant incrase
in SCE frequencies compared to control is observed
STATISTICAL ANALYSIS: Dunnett's test
p-Cresol did not induce significant increases over the control SCE
frequencies. The positive control was functional.
p-Cresol caused a small but statistically significant
decrease in cell-cycle progression at 8 mM (864 mg/l) andabove, indicative of a small cytotoxic response.
(2) valid with restrictions
only tested in the absence of metabolic activation and no information on

272

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
GLP
Critical study for SIDS endpoint

Flag
06.02.2004:

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Ames test
Salmonella typhimurium TA98, TA100, TA1535, TA1537
no data

Reliability:(4) not assignable
documentation insufficient for assessment(159)

with and without
negative
other: according to Ames, Mutation Res. 31, 347 (1975)1980
no dataother TS: p-cresol, not specified further

06.02.2004

(160)

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Unscheduled DNA synthesis
other: human lung fibroblast
no datano datawithpositive
other: no data reported
1978
no dataother TS: p-cresol, not specified further

Reliability:

Flag
06.02.2004:(4) not assignablesecondary literature: description of the test suffers from deficiencies
Critical study for SIDS endpointType
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

other: DNA adduct formation
calf thymus DNA
100 uMno datawithpositive
other: see freetext ME
2001
noother TS: p-cresol, highest analytical grade available

Method:p-Cresol was activated with (1) PB-induced rat liver microsomal protein, (2)horseradish peroxidase and then incubated with calf-thymus DNA
overnight at 37 degree Celcius and adducts were measured by Ppostlabeling analysis .

Result(161):

p-Cresol was oxidized with MnO2 to form a quinone methide and thenincubated with calf-thymus DNA as described above and adducts were
measured
In vitro activation of p-Cresol with
(1) horseradish peroxidase produced six DNA adducts with a relative
adduct level of 8.03 x 10(exp)-7 which were inhibited 65 and 95 % byaddition of either 250 or 500 uM ascorbic acid to the incubation.
(2) PB-induced rat liver microsomes resulted in the formation of a single

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5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
adduct with a relative adduct level of 0.28 x 10(exp)-7.
Oxidized p-Cresol to a quinone methide and than incubated with calfthymus DNA resulted in 5 major adducts and a relative adduct level of
20.38 x 10(exp)-7.

Reliability:

Flag
06.02.2004:

5.6

The DNA adducts formed by activation of p-cresol with either horseradish
peroxidase or microsomes were the same as that produced by the quinone
methide of p-cresol.
(2) valid with restrictions
no validated test method
Critical study for SIDS endpoint(162)

GENETIC TOXICITY ‘IN VIVO‘

TypeSpecies
Sex
StrainRoute of admin.
Exposure period
Doses
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

Dominant lethal assay
mouse
male
ICR
gavageSingle dose
0, 100, 275, 550 (650) mg/kg bw diluted in corn oil
negative
other: EPA OTS 798.5450
1989
yesother TS: p-cresol, 99.8% pure

Method:Dose selection based upon the results of a dose range-finding assay
Number of animals:
25 males/group 50 females/group,
vehicle control: corn oil,positive control: Triethylenemelamine (TEM)
Due to high mortality and toxicity in the 650 mg/kg bw-group during the firstweek mice were removed from the study. Two weeks after the initiation of
the assay another group of males dosed with 550 mg/kg bw was assigned
as the new high dose to be evaluated.
Mating scheme:
1 male was mated with 2 virgin females for a period of up to 5 days. Then
females were removed and housed in groups for subsequent necropsy 14
days after the midweek of mating for evidence of pregnancy; the males
were rested for 2 days and then mated with 2 new females. This mating
sequence was followed for 6 consecutive weeks.
Observation of all animals for toxic effects and/or mortality, at termination
record of male body weight, determination of fertility index, total number of
implantations. dead implantations, proportion of females with 2 or moredead implants, dead implants/total implants

Result274:

Statistical methods:
Chi-square test, analysis of variance (ANOVA), Dunnett's one-tailed t test
Mortality:
650 mg/kg bw: 10/25 males within the first week;
as signs of toxicity mice exhibited rapid breathing, several became languidwith mild clonic convulsions and squinted eyes and were prostrate and had
scruffy coats
550 mg/kg bw: 6/25 males died during the test

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
body weight:
No significant reduction in body weight were observed in any of the males
in any of the dose groups.
The statistical evaluation of the parameters indicated that no significant
effects of p-cresol were induced at any dose levels.
The treatment had no adverse effects with respect to number of early andlate resorptions, and live implants, indicating that the test compound did not
induce dominant lethal mutations in male germ cells of mice under theconditions of this assay.
The concurrent positive control substance TEM induced a significant
increase in :the number of dead implantations, in the portion of females with either one
or more dead implantations, the frequency of dead implants relative to thetotal number of implants in each female during mating weeks 1 through 3
TEM induced a significant reduction in total implants relative to the vehicle
control group.
(1) valid without restriction
Critical study for SIDS endpoint(163)

Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Doses
Result
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Result:Reliability
Flag
06.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Doses
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

Sister chromatid exchange assay
mouse
male
DBA
i.p.
single dose
0, 75 mg/kg bw in sunflower oil
negative
other: see freetext ME
1984
no dataother TS: p-cresol, purity >99%

Method:p-Cresol was administered to 2 or 3 intact or hepatectomized male mice bysingle intraperitoneal injection. After 30 min, DNA labelling was initiatedusing BrdU. After a further 21 hr the animals were killed, cells isolated andharvested and sister chromatid exchange (SCE) frequency in bone marrowcells, alveolar macrophages and regenerating liver cells analysed. Someof the mice were partially hepatectomized to induce liver cell regeneration

Drosophila SLRL test
Drosophila melanogastermaleother: Oregon-R
oral feed
3 days0, 60, 300 and 600 ug/ml 5 % sucrose
negative
OECD Guide-line 477 "Genetic Toxicology: Sex-linked Recessive Lethal
Test in Drosophila melanogaster"1989
yesother TS: p-cresol, 99.8% purity
negative; the treatment did not increase the frequency of sex-linked
recessive lethal mutations, indicating that the test substance was not
mutagenic in Drosophila under the conditions of this assay.
The positive control substance ethylmethansulfonate (EMS) was functional(1) valid without restriction
Critical study for SIDS endpoint(164)

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DATE: 24.05.2004

Result:Reliability:

Flag
06.02.2004:

5.7

NEGATIVE CONTROL: 0.35 ml sunflower oil (4 intact and 5
hepatectomized male mice, bone marrow cells, alveolar macrophages, liver
cells)POSITIVE CONTROL: 5 mg cyclophosphamide/kg bw (2 intact male mice,bone marrow cells, alveolar macrophages).
STATISTICAL ANALYSIS: One way analysis of variance; Dunnett's test forcomparison
p-Cresol did not induce significant increases in SCE
frequencies in any of the cell types examined: bone marrow cells, alveolar
macrophages, liver cells.
The dose tested was overtly toxic to the mice, causing lethargy,
piloerection and lacrimation.
The positive control was functional.
(2) valid with restrictions
only one dose tested, no information on GLP
Critical study for SIDS endpoint(159)

CARCINOGENICITY

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
ResultControl group
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

mouse
femaleother: Sutter
dermal12 weeks (I) or 20 weeks (II)twice weeklyno20 (I) or 5.7 % (II) solutions in benzene

Remark:ResultReliability

:
:

Flag
06.02.2004:

Groups of 20-29 Sutter strain mice:
I. method: initiator: single dermal appl. of 0.3 % 9,10-dimethyl-1,2benzanthracene (DMBA) in acetone; p-cresol (in benzene) was applied as
promotor to the back of each mouse
I. result: 20/28 mice (12/12 benzene control animals);survived andin 35 % (0 % in control animals); skin papillomas were found; no
carcinomas were detected
II. method: initiator: single dermal appl. of 0.3 % DMBA in
benzene; promotor: p-cresol was applied to the back of each mouse
II.result: 14/20 mice (18/20 benzene control animals)
survived and in
29 % (0 % in control animals) skin papillomas were found; no carcinomas
were detected
p-Cresol was evaluated as promotor(2) valid with restrictions
no data on the purity, benzene a known carcinogen as solvent, highmortality rate; no information on skin irritation effects
Critical study for SIDS endpoint(165)

Species
Sex
StrainRoute of admin.
Exposure period

:
:
:
:
:

276

yes, concurrent vehicle
other: tumor promotion test (see freetext RM)
1959
noother TS: p-cresol, not specified further

hamstermaleother: Syrian Golden
oral feed
20 weeks

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5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Frequency of treatm.
Post exposure period
Doses
ResultControl group
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

daily
no
0 or 1.5 % in diet (corresponding to about 1100 mg/kg bw/d)Result:Reliability:

An increased incidence of mild to moderate forestomach
hyperplasia occurred (10 animals: moderate; 5 animals: mild) whencompared with the controls. Marked hyperplasia or papillomatous lesions
were not observed.
(2) valid with restrictions
limited documentation; small number of animals; limited scope of
examinations; short exposure(166)

16.12.2002
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
ResultControl group

:
:
:
:
:
:
:
:
:
:

Method:Year
GLP
Test substance:::

Result:Reliability:

Flag
06.02.2004

:

5.8.1

yes, concurrent no treatment
other: 15 males/group,
1986
no dataother TS: >98% pure.

other: in vitro cell transformation assay
other: mouse BALB/c-3T3 cells

0.81, 3.25, 5, 10, 15 nl/ml culture medium
positive
other: yes, neg control: culture medium with 10 %FCS; pos. control: 3methylcholanthrene
other: 40CFR 795.285 (modified); preliminary cytotoxicity test, performanceof the test according Kakunaga, Int. J.Cancer 12,463,1973, without
metabolic activation
1988
yesother TS: p-cresol, purity: 99.8 %p-cresol produced a dose-related increase in the number of foci/plate overthe entire concentration range. The test material induced celltransformation that was significantly elevated when compared to thecontrols.
Test material toxicity was determined in priliminary assays(2) valid with restrictions
non-validated test system
Critical study for SIDS endpoint(167)

TOXICITY TO FERTILITYType: Two generation study
Species: rat
Sex: male/female
Strain: Sprague-Dawley
Route of admin.
: gavage
Exposure period: see remarks
Frequency of treatm.
: 5 days per week
Premating exposure periodMale: 10 weeks
Female : 10 weeks
Duration of test
: see remarks

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

No. of generation
studies
Doses
Control group
NOAEL parental
other: NOAEL (fertility)
Result
MethodYear
GLP
Test substance

:

2

:
:
:
:
:
:
:
:
:

0, 30, 175, 450 mg/kg bw
yes, concurrent vehicle
ca. 30 mg/kg bw
ca. 450 mg/kg bw
see freetext RS
EPA OPP 83-4
1989
yesother TS: p-cresol, 98.93% pure

Remark

:25 rats/sex/dose (F0) were administered p-cresol in corn oil. Exposure
began 10 weeks prior to breeding and continued in the females throughout
mating, gestation and lactation.
25 randomly selected F1 pups/sex/dose were gavaged with the appropriate
concentration of p-cresol for 11 weeks and then bred to produce F2 litters(dosing was continued throughout mating, gestation and lactation).
The F2 offspring were sacrificed at weaning.
Reproductive Indices: mating indices for males and females, fertility indicesfor male and females, gestational index, live birth index, 4-day survivalindex, 7-day survival index, 14-day survival index, 21-day survival index,
lactation index
Necropsy and pathology:
all F0 and F1 parental rats in all groups were subjected to a complete
necropsy ; 25 male and 25 female adults from the controls and from thehigh dose groups were subjected to histopathology examination: pituitary,
vagina, uterus, ovaries. testes, epididymides, seminal vesicles, prostateand other tissues with gross lesions identified as potentially treatment
related; any of thze above organs or tissues showing gross alterations
were also evaluated microscopically in other dose groups
A complete gross necropsy and histopathologic examination wereconducted for any parental rat dying on test
Gross necropsy included examination of the external surfaces, all orificwes,
cranila cavity, carcass, external and cut surfaces of the brain and spinal
cord, the thoracic,abdominal and pelvic cavities and their viscera, cervicaltissues and organs
a gross internal examination on any F1 and F2 pup appearing abnormal or
dying on test

Result278:

Statistical methods:
Levene's test for equal variances,
analysis of variance (ANOVA),t-test,Kruskal-Wallis test,
Mann-Whitney U test
Fisher's exact test
Mortality: 8/28 males and 5/25 females at 450 mg/kg bw; 1/25 females at
30 mg/kg bw
Clinical signs of toxicity
occurred in F0 and F1 males and females at 450 mg/kg bw/day andincluded hypoactivity, ataxia, twitches, tremors, prostration, urine stains,
audible respiration, perinasal encrustation (not in F0 males), and perioral
wetness occurred at >= 175 mg/kg bw.
body weight:
F0 adult males, sign reduced (p<0.01) week1 to week 13 in the 450 mg/kg
bw group;
F0 adult females:sign. reduced week 1 (p<0.05) in the 450 mg/kg bw-group,

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004
gestational weight gain not significantly different from control group,
lactational body weight sign. reduced (p<0.05) at d4 at 450 mg/kg bw
group
F1 or F2: No reproductive parameters were affected in either of the twogenerations (mating index of male and females, fertility index of males andfemales, gestational index.
Still births in the F1 and F2 generations:in F1 pups increased at 175 mg/kg/day, but not at 450 mg/kg bw) andin F2 pups increased at 30 and 450 mg/kg bw, but not at 175 mg/kg/bw
There was some variability in the number of stillborn in control groups in F1and F2 generation (2 versus 0). There was no clear dose-dependent effectin both generations (control/low/mid/high dose: F1 pups: 2/4/13/6; F2 pups:
0/7/4/9).

Reliability
Flag
06.02.2004
5.8.2

:
:

F1,F2: Pup survival indices in both generations were notaffected by treatment (4-day survival index, 7-day survival index, 14-daysurval index 21-day survival index and lactation index), except live birthindices in F2 (but not F1) which were reduced at 30 and 450 mg/kg bw, but
not at 175 mg/kg/day. Without any other effects especially in the 30 mg/kg
bw-group it is unclear whether the effects on live birth indices were
substance related.
ross lesions of parental males and females which died prior to scheduled
sacrifice included diffuse, focal or multifocal color changes in the lung andstained skin for males and lung congestion and congestion in the nasal
turbinates and erythrocytes on the skin surface for females.
There were no treatment related histologic lesions observed in theexamination of organs from parental F0 and F1 adults which survived toscheduled sacrifice.
(1) valid without restriction
Critical study for SIDS endpoint(168)

DEVELOPMENTAL TOXICITY/TERATOGENICITY

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
NOAEL maternal tox.
NOAEL teratogen.
Method

:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Method:rat
femaleSprague-Dawley
gavagedays 6 - 15
daily
until gd 21
0, 30, 175, 450 mg/kg bw in corn oil
yes, concurrent vehicle= 175 mg/kg bw= 175 mg/kg bw
other: following the TSCA Health Effects Test guidelines for SpecificOrgan/Tissue Toxicity - Developmental Toxicity (EPA, 1984,1987)
1988
yesother TS: p-cresol, purity = 98.93%
Dose selection was based on the results of a range-finding study.
25 mated females/group, 50 control females, all females were weighed on
gd 0, 6, 11, 15, and 21, food consumption was measured throughout
gestation, all females were examined daily for clinical signs, for mortality
and morbidity
sacrifice on gd 21:
does were evaluated for body weight, liver and gravid uterine weight,

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Resultp-CRESOL
ID: 106-44-5
DATE: 24.05.2004:

number of corpora lutea and number and status of implantation sites (i.e.
resorptions, dead fetuses, live fetuses)
live fetuses were dissected from uterus, counted and weighed, examinedfor external malformations and variations, and for visceral malformaltionsand variations, and for soft tissue craniofacial malformations
statistical analysis:
Levene's test, ANOVA, pooled t-test, Kruskal-Wallis test, Mann-Whitney Utest, Fisher's exact test
Maternal toxicity:
mortality: 3/25 females at 450 mg/kg bw/day
No abortions or early deliveries (1 litter at 30 mg/kg bw was fully resorbed)
450 mg/kg bw:
decreased food consumption
stat. sign. reduction in periodic maternal body weight and weight gain
during dosing, maternal gestational weight gain reduced when corrected forthe weight of the gravid uterus and reduced maternal terminal bw, relative
but not absolute liver weight was increased
clin. signs of toxicity: hypoactivity, ataxia and tremors, prone position
audible respiration and perioral wetness
gestational parameters were unaffected by treatment except fetal bodyweight per litter were reduced at 450 mg/kg bw.
fetal evaluations:
No significant changes in the incidence of any individual malformation,
malformation by category (external, visceral including craniofacial or
skeletal) or total malformations for any dose group.
450 mg/kg bw:
7 skeletal variations exhibited sign. different incidences relative to those in
the control groups:
incidence of cervical centrum 6 bilobed, reduced number of ossified caudal
segments, unossified sternebrae, reduced incidence of unossified cervicalcentrum no. 7, poorly ossified parietal skull bone (30 mg/kg bw), reduced
incidence of some (1-4) proximal phalanges of the hind limb unossified

Reliability
Flag
06.02.2004::

Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
NOAEL maternal tox.
NOAEL teratogen.
Result
Method

:
:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance

:
:
:

280

p-Cresol caused mild fetotoxicity at the 450 mg/kg, as seen
by reduced ossification in three skeletal districts. In
addition, fetal body weight was reduced at the 450 mg/kg doselevel. There was no treatment-related increased incidence ofmalformations at any dosage.
(1) valid without restriction
Critical study for SIDS endpoint(169)
rabbitfemaleNew Zealand whitegavagedays 6 - 18 of gestation
daily
until gd 29
0, 5, 50, 100 mg/kg bw in corn oil
yes, concurrent vehicle= 5 mg/kg bw= 100 mg/kg bw
see freetext ME
other: following the TSCA Health Effects Test guidelines for SpecificOrgan/Tissue Toxicity - Developmental Toxicity (EPA, 1984,1987)
1988
yesother TS: p-cresol, purity = 98.93%

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Remark:Result:Reliability
Flag
06.02.2004

:
:

5.8.3

Dose selection was based on the results of a range-finding study.
14 mated females/group, 28 control females, all females were weighed on
gd 0, 6, 12, 18, 24 and 29, food consumption was measured throughout
gestation, all females were examined daily for clinical signs, for mortality
and morbidity
sacrifice on gd 29:
does were evaluated for body weight, liver and gravid uterine weight,
number of corpora lutea and number and status of implantation sites (i.e.
resorptions, dead fetuses, live fetuses)
live fetuses were dissected from uterus, counted and weighed, examinedfor external malformations and variations, and for visceral malformaltionsand variations, and for soft tissue craniofacial malformations
statistical analysis:
Levene's test, ANOVA, pooled t-test, Kruskal-Wallis test, Mann-Whitney Utest, Fisher's exact test
mortality: 100 mg/kg bw: 5/14; 50 mg/kg bw: 2/14;
all were pregnant
1 control female aborted and one each at 5.0 and 50 mg/kg bw wasremoved due to dosing error
gestational weights and weight changes were not stat. significant different
among groups for periodic body weights or weight changes.
50, 100 mg/kg bw: clinical signs included hypoactivity, gasping, cyanosis,
laboured rapid and audible respiration and ocular discharge
food consumption: no significant differences among groups for any time
period measured; no treatment related gross lesions at necropsy of does
maternal organ weights:
no significant difference among the groups: terminal bw., gravid uterine
weight, corrected bw. or weight change, absolute and relative liver weightgestational parameters:
no significant difference for number of ovarian corpora lutea, number of
implantations sites including total, nonviable (early or late resorptions ordead fetuses) or viable percent live fetuses per litter or fetal body weight
per litter; sex ratio was significantly increased (more males) at 50 mg/kg bw
but not at 100 mg/kg bw (considered due to biological variabilty)
fetal evaluation:
No significant differences among groups for any individual malformations,malformations by category or total malformations; no treatment-related
significant differences for any individual external variations, variations by
category or total variations.
(1) valid without restriction
Critical study for SIDS endpoint(170)

TOXICITY TO REPRODUCTION, OTHER STUDIESType
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result
Method

:
:
:
:
:
:
:
:
:
:
:
:
:

other
In vivo
mouse
male/female
B6C3F1oral feed
28 dcontinuously in diet28 d0, 300, 1000, 3000, 10000, 30000 ppm
yes, concurrent no treatment
See freetxt RS
other: the reproductive organs were examined as part of the 28-day study,
see chapter 5.4

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Year
GLP
Test substance

:
:
:

1991
yes
other TS: p-cresol, Purity > 98 %Result:Reliability
06.02.2004:

Histopathological examination revealed no effects on the reproductive
organs.
(1) valid without restriction

Type
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result

:
:
:
:
:
:
:
:
:
:
:
:

Method:Year
GLP
Test substance

:
:
:

other
In vivoratmale/female
Sprague-Dawley
gavage134 weeks
daily
14 weeks
0, 50,175, 600 mg/kg bw dissolved in corn oil
yes, concurrent vehicle
600 mg-gr.: death of 3 females, decreased ovary weights; males: increased
testes weight
other: the reproductive organs were examined as part of the 13 week
toxicity study, see chapter 5.4
1986
yesother TS: p-cresol, purity 99.9 %Reliability
Flag
06.02.2004::(1) valid without restriction
Critical study for SIDS endpoint

5.9

(150)

(151)

SPECIFIC INVESTIGATIONS

Endpoint
Study descr. in chapter
Reference
Type
Species
Sex
StrainRoute of admin.
No. of animals
VehicleExposure period
Frequency of treatm.
Doses
Control group
Observation period
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Neurotoxicity
5.9 Specific Investigations

Method:10 male and 10 female CD rats/treatment group received corn oil solutionsof 50, 175 or 600 mg/kg bw /day by gavage once daily for 13 weeks. 20
male and 20 female CD rats received corn oil alond to serve ascontrol.Rats were observed for body weight gain, food consumption,clinical signs.

282

other: subchronicratmale/female
other: CDgavage20
other: corn oil
90 day(s)once daily
0, 50, 175, 600 mg/kg bw
yes, concurrent vehicle
13 weeks during dosing
see freetext RS
other: see freetext ME
1986
no dataother TS: purity: no data

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p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

Result:Reliability:

Flag
04.02.2004

:

5.10

Signs of neurobehavioral toxicity were documented during pretreatment, 1
and 6 hours after dosing on study day 1 and prior dosing on study days 2,
7, 14, 30, 60 and 90 including salivation, urination, tremors, piloerection,
diarrhea, pupil size, pupil response, lacrimation, hypothermia, vocalization,
exophthalmus, palpebral closure, convulsions (type and severity),
respiration (rate and type), impaired gait, positional passivity, locomotor
activity, stereotypy, startle response, righting reflex, performance on a wire
maneuver, forelimb grip strength, positive geotropism, extensor thrust, limb
rotation, tail pinch reflex, toe pinch reflex, hind limb splay.
gross and histopathologic examination
Mortality: control: 1 female(2.5 %), 600 mg-gr: 4 males and 4 females (40%), gross and histopathologic examination: aspiration or inhalation of theTS, pulmonary edema
body weight gain: 600 mg-gr., males less than control during week 1mean food consumption, 600 mg-gr., males and females: significantly lessthan control
clinical signs: dose related in incidence: salivation, myotonus, tremors,urine wet abdomen, hypoactivity, rapid respirationneurobehavioral toxicity:
600 mg-group, males and females: initial part of the study: incidence of
palpebral closure, rales, laboured respiration; locomotor activity less thanconcurrent controls; at study termination: a trend towards increased
urination.
Other differences from controls with regard to behavioral tests were
evaluated as sporadic in nature by the authors (no further details given).
necropsy:brain weights of treated animals comparable to controls; gross andmicroscopic examination of tissues revealed no lesions which were
attributable to treatment(2) valid with restrictions
limited documentation (only study summary available)
Critical study for SIDS endpoint(145) (129) (171)

EXPOSURE EXPERIENCE

Remark:Reliability
Flag
15.01.2003::

RemarkReliability
Flag
10.01.2003:::

In vitro production of p-cresol from tyrosine by bacteria
isolated from normal human gut was examined. Strictly
anaerobic and facultatively anaerobic bacteria were grown
at 37oC in the presence of 0.01% tyrosine for 72 and 48 hr
respectively. The growth atmospheres for the bacteria were
nitrogen, hydrogen and carbon dioxide and air respectively.
p-Cresol production from tyrosine was seen with thestrictly anaerobic gut bacteria but not the facultatively
anaerobic bacteria. p-Cresol is, therefore, produced
endogenously from tyrosine, an amino acid present in mostproteins, by strictly anaerobic bacteria in the intestine.
According to the results of studies in cancer patients, endogenous p-Cresol
does not contribute significantly to the development of large bowl caner(18 patients versus 10 normal healthy persons.
(2) valid with restrictions
Critical study for SIDS endpoint(133)
The probable oral lethal dose for humans is 50-500 mg/kg bw.
(2) valid with restrictions
Critical study for SIDS endpoint(172)

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DATE: 24.05.2004

Remark:Reliability:

Flag
14.01.2003:

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
17.01.2003::

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag

:
:

284

Case reports: intentional or accidental oral intake of cresols (all isomers):
irritation of mouth and throat, abdominal pain, vomiting, hemolytic anemia,
increased heart ratem liver and kidney damage, headaches, facial
paralysis, drowsiness, cramps coma and death(2) valid with restrictions
description suffers from deficiencies as the isomers are not specified
Critical study for SIDS endpoint(173) (174) (175) (176)
It is reported that certain individuals are hypersensitive tocresol (isomer not specified, no further information)(4) not assignable
Critical study for SIDS endpoint(127)
Skin depigmentation (chemical leukoderma has been reported after local
exposure to cresols (isomer not specified)(4) not assignable
Critical study for SIDS endpoint(150)
It is reported that skin contact has alo resulted in effects on the nervous
system, liver and kidneys and caused human fatalities.
(4) not assignable
Critical study for SIDS endpoint(175)
A cresol solution, unintentionally poured over the trunk, caused grosshematuria, gastrointestinal bleeding, hypertension and septic shock withsevere jaundice and renal failure.
(2) valid with restrictions
Critical study for SIDS endpoint(177)
The development of tumours in persons who had been exposed
occupationally to cresol (unspecified isomer) has been reported, and twocases of transitional cell bladder carcinoma were described after longterm
exposure to cresol. since no information on exposure levels are available
and since co-exposure to other ssubstances cannot be excluded a
carcinogenic potential of the cresol isomers cannot be deduced fron thesecases.
(2) valid with restrictions
Critical study for SIDS endpoint(178)
Case report: a worker in an oil rafinery was exposed to cresol,
dichlorooctane and chromic acid for a long period developed a squamous
epithelial carcinoma of the vocal cords. Since no information on exposurelevels is available and since co-exposure to other substances is included a
carcinogenic potential of the cresol isomers cannot be deduced from thiscase report.
(4) not assignable
Critical study for SIDS endpoint

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004

15.01.2003(175)

Remark:Reliability
Flag
15.01.2003::

Remark:Reliability
Flag
15.01.2003

:
:

5.11

Anomalous menstrual cycles were found and hormonal disorders werereported from women who were employed in ther production to enamelledwire or of tricresyl phosphate and were exposed to a variety ofcompounds, including chlorobenzenes and phosphoryl chloride. It wasclaimed that the incidence of perinatal child death was increased and thatdevelopmental disorders were frequent among new-born babies. since nodata on exposure levels and duration of exposure are given and data on
controls were not provided a relationship between fthe described effects
and cresol exposure cannot be deduced.
(4) not assignable
Critical study for SIDS endpoint(175)
According to the results of studies in patients, endogenous p-Cresol does
not contribute significantly to the development of human bladder (32patients vs 32 age/sex-matched controls).
(2) valid with restrictions
Critical study for SIDS endpoint(132)

ADDITIONAL REMARKSUNEP PUBLICATIONS

285

OECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(1)

Internal communication Degussa Corporation, 2003

(2)

Deutsche Forschungsgemeinschaft, MAK- und BAT-Werte-Liste 2001, Senatskommission
zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 37, VCH Verlagsgesellschaft
mbH, Weinheim 2001.

(3)

Auer Technicum, 12. Ausgabe. Auergesellschaft Berlin, 398-399 (1989)(4)

Verschueren K (1996) Handbook of Environmental Data on Organic
Chemicals. John Wiley & Sons Inc(5)

Weast, R.C. (1990) CRC Handbook of Chemistry and Physics. 1989-1990. 70th ed. Boca
Raton, Florida. CRC Press Inc. c-220.

(6)

Sax NI and Lewis RJ (1987) Hawley's Condensed Chemical
Dictionary, 11th Edition. Van Nostrand Reinhold Company, New
York

(7)

Lide, D.R. (2002), CRC Handbook of Chemistry and Physics, 82st ed. CRC Press Inc.,
Boca Raton, 3-257(8)

Merck Index. (1996) 12th Ed. Rahway, New Jersey. Merck Co. Inc. p 437.

(9)

Bayer AG, Safety data sheet (2001-07-31)(10)Lide, D.R. (1996) CRC Handbook of Chemistry and Physics. 1995-1996. 76th Ed., CRC
Press Inc. Boca Raton, p. 3-257, #9402.

(11)

Daubert TE and Danner RP (1989) Physical and thermodynamic
properties of pure chemicals: data compilation, experimentally determined data, cited in
SRC-MBBPWIN v 1.40

(12)

Hansch, C. et al. (1995) Exploring QSAR. Hydrophobic, Electronic, and Steric Constants.
ACS Professional Reference Book. Washington, DC: American Chemical Society (1995),
experimental data, cited in SRC-KowWin v.1.66(13)

Hansch C and Leo A (1979) Substituent Constants for Correlation Analysis in Chemistry
and Biology. John Wiley & Sons

(14)

Yalkowsky SH and Dannenfelser RM (1992) Aquasol database of aqueous solubility.
Version 5.; College of Pharmacy, University of Arizona - Tucson, AZ. PC Version,
experimentally determined data, cited in SRC-WSKOW v1.40(15)Ferguson SB, Sanford EM, Seward EM, Diederich F (1991) Cyclophane-arene inclusion
complexation in protic solvents: Solvent effects versus electron donor-acceptor
interactions. J. Amer. Chem. Soc., 113: 5410-5419(16)

Scully FE and Hoigne J (1987) Chemosphere 16 (4), 681-694(17)

Pearce PJ and Simkins RJJ (1968) Can J Chem 46, 241-248(18)Chuchani G and Frohlich A (1971) J Chem Soc (B): 1417-1419(19)Dietz F and Traud J (1978) GWF-Wasser/Abwasser 119: 318-325(20)

Bayer AG (2003): Calculation of indirect photodegradation with AOPWIN(21)

Semadeni M, Stocker DW, Kerr JA (1995) Int. J. Chem. Kinet. 27: 287-304

286

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(22)

Atkinson R (1989) J. Phys. Chem. Ref. Data, Monograph No.1:
Gas-Phase Tropospheric Chemistry of Organic Compounds(23)

Atkinson R (1994): J. Phys. Chem. Ref. Data, Monograph No.2: Gas-Phase Tropospheric
Chemistry of Organic Compounds(24)

Atkinson R and Carter WPL (1984) Chem. Reviews 84, 437-470(25)

Atkinson R and Aschmann SM (1990) Int. J. Chem. Kinet. 22: 59-67(26)

Atkinson R (1987) Intern. J. Chem. Kinet. 19: 799-828(27)

Atkinson R, Darnall KR, Lloyd AC, Winer AM, Pitts JN (1979) Adv. Photochem. 11: 375488(28)

Atkinson R, Darnall, KR, Pitts, JN (1978) J. Phys. Chem. 82: 2759 - 2761

(29)

Canonica S and Hoigne J (1995) Chemosphere 30 (12): 2365-2374(30)

Choudry GG (1983) Toxicol. Environ. Chem. 6: 231-257 (secondary citation)(31)

Smith JH, Mabey WR, Bohonos N, Holt BR, Lee SS, Chou T-W, Bomberger DC, Mill T(1978) Environmental Pathways of Selected Chemiclas in Freshwater Systems. Part II:
Laboratory Studies. US EPA-600/7-78-074: 22, 58, 82, 110, 135, 158, 186, 209, 232, 268(32)

Anbar M and Neta P (1967) Int. J. Appl. Radiat. Isotopes 18: 493-523(33)

Evangelista RA, Allen HL, Mandel RM (1990) J. Hazard. Mater. 25(3): 343-360(34)

Gaffney JS, Streit GE, Spall WD, Hall JH (1987) Beyond acid rain. Environ. Sci. Technol.
21 (6), 519-523(35)

Boyd SA (1982) Soil Sci. 134(5): 337-343(36)Southworth GR and Keller JL (1986) Water Air Soil Pollut. 28, 239-248(37)

Meylan W and Howard P (1992) Environ. Sci. Technol. 26: 1560-1567(38)

Artiola-Fortuny J and Fuller WH (1982) Soil Science 133 (1), 18-26(39)

SRC-Environmental fate database, Chemfate search for p-Cresol (2002)(40)

Bayer AG (2002): calculation of the environmental distribution of p-cresol according tofugacity model Mackay level I(41)

Desai S, Govind R, Tabak H (1990) ACS Symp. Ser. 422: 142-156(42)

Van Veld PA and Spain JC (1983) Chemosphere 12 (9/10): 1291-1305(43)

Wellens H (1990) Z. Wasser Abwasser Forsch. 23: 85-98(44)

Pitter P (1976) Determination of biological degradability of organic substances. Water
Research 10: 231-235(45)

Shelton DR and Tiedje JM (1981) Development of test for
determining anaerobic biodegradation potential. NTIS Report[PB 84-166495], Springfield(46)

Shelton DR and Tiedje JM (1984) Appl. Environ. Microbiol. 47: 850-857

UNEP PUBLICATIONS

287

OECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(47)

Battersby NS and Wilson V (1988) Chemosphere 17(12): 2441-2460(48)

Battersby NS and Wilson V (1989) Appl. Environ. Microbiol. 55: 433-439(49)

Spain JC and van Veld PA (1983) Appl. Environ. Microbiol. 45: 428-435(50)

Boyd TJ and Carlucci AF (1993) Aquat. Toxicol. 25, 71-82(51)

Vaishnav DD and Korthals ET (1988) Bull. Environ. Contam. Toxicol. 41: 291-298(52)

Vaishnav D, Babeu L, Korthals ET (1989) J. Industr. Microbiol. 4: 307-314(53)

Hwang H-M, Hodson RE, Lewis DL (1989) Environ. Toxicol. Chem. 8, 65-74(54)

Delfino JJ and Miles CJ (1985) Soil Crop Sci. Soc. Proc. 44: 9-14

(55)

Fedorak PM and Hrudey SE (1984) Water Res 18: 361-7(56)Babeu L and Vaishnav DD (1987) J. Industr. Microbiol. 2: 107-115(57)

Kollig HP, Parrish R, Holm H (1987) Chemosphere 16(1): 49-60(58)

Liu D and Pacepavicius G (1990) Toxicity Assessment 5(4), 367-387(59)

Govind R, Flaherty PA, Dobbs RA (1991) Water Res. 25(5), 547-556(60)

Parker WJ, Monteith HD, Melcer H (1994) Water Res. 28: 1779-1789(61)

Madsen T, Rasmussen H, Nilsson L (1995) Chemosphere 31(10): 4243-4258(62)

Horowitz A, Shelton DR, Cornell CP, Tiedje JM (1982) Dev. Ind. Microbiol. 23, 435-444(63)

Young LY and Rivera MD (1985) Water Res. 19(10), 1325-1332(64)

Roberts DJ, Fedorak PM, Hrudey SE (1987) Can. J. Microbiol. 33, 335-338(65)

Boyd SA, Shelton DR, Berry D, Tiedje JM (1983) Appl. Environ. Microbiol. 46: 50-54(66)

Wang Y-T, Suidan MT, Pfeffer JT, Najam I (1989) Biotechnol. Bioeng. 33: 1353-1357(67)

Kuhn EP, Zeyer J, Eicher P, Schwarzenbach RP (1988) Appl. Environ. Microbiol. 54(2),490-496(68)

Smolenski WJ and Suflita JM (1987) Appl. Environ. Microbiol. 53: 710-716(69)

Kaminski U, Kuschk P, Janke D (1990) J Basic Microbiol 30: 259-265(70)

Häggblom MM, Rivera MD, Bossert ID, Rogers JE, Young LY (1990) Microb. Ecol. 20: 141150(71)

Pauli O and Franke G (1972) Biodeterior. Mater. Proc. Int. Biodeterior. Symp. 2, 52-60(72)

Alexander M and Lustigman BK (1966) J. Agric. Food Chem. 14(4): 410-413(73)

Arvin E, Jensen B, Godsy EM, Grbic-Galic D (1989) Microbial degradation of oil andcreosote related aromatic compounds under aerobic and anaerobic conditions. Int. Conf.
Physiochem. Biol. Detoxif. Hazard. Wastes 2: 828-847(74)

Kondo M, Nishihara T, Shimamoto T, Koshikawa T, Ito T, Sawamura R, Tanaka K (1988)
Eisei Kagaku 34(2): 188-185

288

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(75)

McKim J, Schmieder P, Veith G (1985) Toxicol. Appl. Pharmacol. 77: 1-10

(76)Suflita JM, Liang L, Saxena A (1989) J. Industr. Microbiol. 4: 255-266(77)

Masunaga S, Urushigawa Y, Yonezawa Y (1985) Kogai Shigen Kenkyusho Iho 15: 87-96(78)

Geiger DL, Poirier SH, Brooke LT, Call DJ (1986) Acute Toxicities of Organic Chemicals to
Fathead Minnows (Pimephales Promelas), Vol. III. Center for Lake Superior Environmental
Studies, University of Wisconsin-Superior(79)

DeGraeve GM, Geiger DL, Meyer JS, Bergman HL. (1980) Acute and embryo-larval toxicityof phenolic compounds to aquatic biota. Arch. Environ. Contam. Toxicol. 9: 557-568(80)

Howland RM (1969) Investigations in Fish Constrol 34: 1-10, US
Department of the Interior, Bureau of Sport Fisheries andWildlife(81)

Hodson, P.V., D.G. Dixon, and K.L.E. Kaiser (1984) Measurement of median lethal dose asa rapid indication of contaminant toxicity to fish. Environ. Toxicol. Chem. 3(2), 243-254(82)

Barron MG and Adelman IR (1984) Canad. J. Fish. Aquat. Sci. 41(1): 141-150(83)

Kanabur VV and Sangli AB (1998) Environ. Ecol. 16(2): 334-336(84)

Falk-Petersen IB, Kjorsvik E, Lonning S, Moller Naley A, Sydnes LK (1985) Sarsia 70, 1116

(85)

Mattson V, Arthur JW, walbridge CT (1976) Acute Toxicity of Selected Organic Compounds
to Fathead Minnows. US-EPA, Report No.
EPA-600/3-76-097(86)

Sangli AB, Kanabur VV (2000) Acute toxicity of cresol and chlorophenol to a freshwater
Gambusia affinis and their effects on oxgen uptake. Journal of Environmental Biology 21(3): 215-217(87)

Ruebelt C, Dietz F, Kickuth R, Koppe P, Kunte H, Peschel G, Sonneborn M (1982)
Schadstoffe im Wasser. Band II, Phenole.
Boldt Verlag, Boppard, S. 101-115(88)

Tiedge H, Nagel R, Ulrich K (1986) Bull. Environ. Contam. Toxicol. 36, 176-180(89)

Kanabur VV, Sannadurgappa D (2001) Acute toxicity of phenol and cresol to a freshwater
fish Oreochromis mossambicus. Environment & Ecology 19 (4): 756-758(90)European inland fishery advisory commission, working party
on water quality criteria for European fresh water fish,
Water Res. 7, 929-941 (1973)(91)

Bergman, H.L. and Anderson, A.D (1977). Effects of Aqueous Effluents from In Situ Fossil
Fuel Processing Technologies on Aquatic Systems. Contract No. EY-77-C-04-3913,
University of Wyoming, Laramie, WY.

(92)

Kühn R, Pattard M, Pernak KD, Winter A (1988) Schadstoffwirkungen von
Umweltchemikalien im Daphnien-Reproduktionstest als Grundlage für die Bewertung der
Umweltgefährlichkeit in aquatischen Systemen. Institut für Wasser-, Boden- undLufthygyene des Bundesgesundheitsamtes(93)

Kühn R, Pattard M, Pernak KD, Winter A (1989) Water Res. 23(4): 501-510(94)

Kühn R, Pattard M, Pernak KD, Winter A (1989) Water Res. 23(4): 495-499

UNEP PUBLICATIONS

289

OECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(95)

Devillers J (1988) Sci. Total Environ. 76: 79-83(96)

Devillers J, Chambon P, Zakarya D, Chastrette M, Chambon R (1987) Chemosphere 16:1149-1163(97)

Parkhurst BR, Bradshaw AS, Forte JL, Wright GP (1979) Bull. Environ. Contam. Toxicol.
23: 349-356(98)

Bringmann G and Kuehn R (1959) Gesund.Ing. 80: 115-120(99)

Kühn R and Pattard M (1990) Water Res. 24(1): 31-38(100)

Huang JC and Gloyna EF (1968) effect of organic compounds on photosynthetic
oxygenation 1. Chlorophyll destruction and suppression of photosynthetic oxygen
production. Water Res 2: 347-366(101)

Nobel W, Mayer T, Kohler A (1983) Z. Wasser Abwasser Forsch. 16 (3), 87-90(102)

Batterton J, Winters K, Van Baalen C (1978) Science 199: 1068-1070(103)

Robinson JM, Allen BE, Denton TE (1976) J. Alabama Acad. Sci. 47, 243-246(104)

Stout J and Kilham SS (1983) Bull. Environ. Contam. Toxicol. 30(1): 1-5(105)

Chan C-M, Lo W, Wong K-W, Chung W-F (1999) Chemosphere 39 (9), 1421-1432(106)

Tomlinson TG, Boon, AG, Trotman CNA (1966) J. Appl. Bact. 29 (2), 266-291(107)

Blum DJW and Speece RE (1991) Research Journal WPCF 63 (3): 198-207(108)

Schultz TW, Bryant SE, Kissel TS (1996) Bull. Environ. Contam. Toxicol. 56: 129-134(109)

Schultz TW, Kyte LM, Dumont JN (1978) Arch. Environm. Contam. Toxicol. 7: 457-463(110)

Yoshioka Y, Ose Y, and Sato T (1985) Testing for the toxicity ofChemicals with Tetrahymena pyriformis. Oxyge. Sci. Total
Environ. 43(1-2), 149-157(111)

Bringmann G and Kuehn R (1960) Gesund.Ing. 81, 337-339(112)

Hartung, J. (1987) Toxicity Assessment 2 (1), 1-15

(113)

Kanne R, Rast HG, Springer W (1986) Analytik bakterientoxischer Effekte mit Hilfe
genetisch konstruierter Leuchtbakterien. Z Anal Chem 325 (1): 136 - 139(114)

Lebsack ME, Anderson AD, DeGraeve GM, Bergman HL (1981) Aquatic Toxicology andHazard Assessment: Fourth Conference, ASTM STP 737, D.R.Branson and K.L. Dickson,
Eds., American Society for Testing and Materials: 348-356(115)

Botsford JL, Rivera J, Navarez J, Riley R, Wright T, Baker R (1997) Bull. Environ. Contam.
Toxicol. 59: 1000-1009(116)

Solski A and Piontek M (1987) Pol. Arch. Hydrobiol. 34 (4): 543-550(117)

Yatagai M and Unrinin G (1989) Mokuzai Gakkaishi 35, 1021-1028(118)

Reynolds T (1978) Ann. Bot. 42, 419-427(119)

Schafer EW Jr, Bowles WA Jr, Hurlbut J (1983) Arch. Environm. Contam. Toxicol. 12: 355382

290

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(120)

Schroth MN and Hildebrand DC (1968) Phytopathol. 58, 848-854(121)

Roberts MS, Anderson RA, Swarbrick J (1977) Permeability of human epidermis to thephenolic compounds. J Pharm Pharmac 29: 677-683(122)

Bray HG, Thorpe WV, White K (1950) Metabolism of derivatives of toluene. Biochem J 46:
275-278(123)

DeBruin A (1976) Metabolism of occupational agents. In: Biochem Toxicol Environm
Agents: Elsevier/North-Holland Biomedical Press, Amsterdam, p. 87-170(124)

Gadaskina ID and Filov VA (1971) Transformations and determination of industrial poisonsin the human body. Leningrad, Meditsina, pp. 202-205, as cited in: IPCS (1995).
Environmental Health Criteria for Cresols. First draft. PCS/EHC/93.24. International
Programe on Chemical Safety(125)

Pereima VL (1975) Inhalational effect of cresol isomers at low concentrations and means
for improving detoxication processes in experiments on white rats. Dissertation, Lvov, pp.
86-90, cited in: IPCS (1995), Environmental Health Criteria Report No. 168 : Cresols,International Programme on Chemical Safety(126)

Pereyman V.(1977) Cytotoxicity of cresol isomers in aerosol in subtoxic concentrations.
Vrachebvnoe Delo 5: 126-130(127)

Deichmann WB and Keplinger ML (1981) Phenols and phenolic compounds. In: Clayton
GD and Clayton FE (Ed.) Patty's industrial hygiene and toxicology. 3rd rev ed Vol 2A, Wileyand Sons, New York, 2597-2601(128)

Wandel O (1907) Zur Pathologie der Lysol- und Kresolvergiftung. Arch Exp Pathol
Pharmacol 56: 161-186(129)

IPCS (1995) (International Programme on Chemical Safety): EHC (Environmental HealthCriteria) No. 168: Cresols, WHO, Geneva(130)

Mandel H.G. (1971) Pathways of Drug Biotransformation: Biochemical Conjugations in
LaDu B.N., Mandel H.G. and Way E.L. (eds.) Pathway of drug biotransformation:
biochemical conjugations, Williams and Wilkins, Baltimore, pp: 149-186(131)

Scheline Ronald R. (1973) Metabolism of foreign compounds by gastrointestinal
microorgamisms, Pharmacological Reviews 25, 451-523(132)

Renwick A.G. et al. Microbial amino acid metabolites andbladder cancer: No evidence of promoting activity in man.
Hum. Toxicol. 7: 267-272, 1988.

(133)

Bone E, Tamm A, Hill M (1976) The production of urinary phenols by gut bacteria and their
possible role in the causation of large bowler cancer. Am J Clin Nutr 29: 1448-1454(134)

Thompson DC, Perera K, London R (1996) Studies on the mechanism of hepatotoxicity of
4-methylphenol (p-cresol): effects of deuterium labeling and ring substitution. Chem-Biol
Interact 101, 1-11

(135)

Schaltenbrand WE and Coburn SP (1985) Determination of phenol and p-cresol in urine.
Clin Chem 31: 2042-2043(136)

Deichmann WB and Witherup S (1944) Phenolic studies VI: The acute and comparative
toxicity of phenol and o-, m-, and p-cresols for experimental animals. J Pharmac Exp Ther
80: 233-240

UNEP PUBLICATIONS

291

OECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(137)

Hazleton Laboratories America Inc. (1989) HLA Study No. 10003-0-459DL, Single acuteexposure dose selection study on para-Cresol, submitted to Chemical Manufacturers
Association (Sponsor study number CRE 9.0-DL-HLA)(138)

Uzhdavini ER, Astaphieva AA, Mamaeva WG (1976) Materials for establishing the limiting
dose of dicresol in the air at production premises. Gig Truda Prof Zabol 9: 53-55 as cited in
IPCS (1995)(139)

Bio-Fax Ind. Bio-Test Lab. Inc. (1969) Toxicity data sheet for p-cresol5-5/69, unpublishedstudy by Bio-Fax Industrial Bio-Test Labs. EPA/OTS205862(140)

Vernot EH, MacEwen JD, Haun CC, Kinkead ER (1977) Acute toxicity and skin corrosion
data for some organic and inorganic compunds and aqueous solutions. Toxicol Appl
Pharmacol 42, 417-423(141)

Uzhdavini ER, Astraphieva IK, Mamaeva AA (1974) Acute toxicity of the lower phenols. Gig
Truda Prof Zabol 2: 58-59 as cited in IPCS (1995)(142)

Angel A and Rogers KJ (1972) An analysis of the convulsant activity of substituted
benzenes in the mouse. Toxicol Appl Pharmacol 21: 214-229(143)

Sternitzke A, Legrum W, Netter KJ (1992) Effects of phenolic smoke condensates and theircomponents on hepatic drug metabolizing systems. Fd Chem Toxic 30: 771-781(144)

Tollens K (1905) Über die Wirkung der Cresole und des Liquor Cresoli Saponatus im
Vergleich zur Carbolsäure. Arch Exp Path Pharm 52: 220-241(145)

ATSDR (1990) Draft toxicological profile for cresols: o-cresol, p-cresol, m-cresol. Agency
for Toxic Substances and Disease Registry, US Public Health Service(146)

Bayer AG (1994) EUCLID datasheet on m-cresol(147)

Campbell I (1941) Petroleum cresylic acids: A study of their toxicity and the toxicity ofcresylic disinfectants. Soap Sanit Chem 17: 103-111, 121(148)

Kligman AM (1972) Report to RIFM, 22. November, cited in: Opdyke DLJ, Fragrance raw
materials monographs. p-Cresol. Fd Cosmet Toxicol 12: 389-390, 1974

(149)

Sharp DW (1978) The sensitization potential of some perfume ingredients tested using amodified draize procedure. Toxicology 9: 261-271(150)

NTP (1991) Toxicity studies of cresols (CAS Nos 95-48-7, 108-39-4, 106-44-5) in F344/N
rats and B6C3F1 mice (feed studies), NTP-Tox 9. Research Triangle Park, NC, U.S.
Department of Health and Human Services, Public Health Service, National Institutes of
Health, National Toxicology Program(151)

Microbiol. Associates Inc., Mulligan LT (1988) Subchronic toxicity of meta-cresol inSprague-Dawley rats, MBA Chemical No: 25, Study No. 5221.08, Final Report, Bethesda,
USA (at the request of Research Triangle Instiute: Dennis Dietz)(152)

Shelley WB (1974) p-Cresol: Cause of ink-induced hair depigmentation in mice. British
Journal of Dermatology 90: 9-174(153)

Haworth S, Lawlor F, Mortelmans K, Speck W, Zeiger E (1983) Salmonella mutagenicity
test results for 250 chemicals. Environ Mutagen 5, Suppl. 1: 3-142(154)

Hazleton Laboratories America, Inc. (1988) HLC study no: 10003-0-437, Mutagenicity teston para-Cresol CP 945: In an in-vitro cytogenetic assay measuring chromosomal
aberration frequencies in Chinese Hamster Ovary (CHO) cells. June 28, 1988 (at therequest of CMA, USA), EPA/OTS0517691

292

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(155)

Hazleton Laboratories America Inc. (1988) HLA Study No. 10002-0-431 Mutagenicity test
on meta-cresol in a mouse lymphoma mutation assay, Kensington, USA (at the request of
CMA), EPA-OTS0517693(156)

Daugherty JP and Franks H (1986) Effect of monocyclic derivatives on DNA repair inhuman lymphocytes. Res Commun Chem Path Pharmac 54: 133-136(157)

Jansson T, Curvall M, Hedin A, Enzell CR (1986) In vitro studies of biological effects ofcigarette smoke condensate II. Induction of sister-chromatid exchanges in human
lymphocytes by weakly acidic, semivolatile constituents. Mutation Res 169: 129-139(158)

Pool BL and Lin PZ (1982) Mutagenicity testing in the Salmonella Typhimurium assay ofphenolic compounds and phenolic fractions obtained from smokehouse smoke
condensates. Food Chem Toxicol 20: 383-391(159)

Cheng M and Kligerman AD (1984) Evaluation of the genotoxicity of cresols using sisterchromatid exchange (SCE). Mutation Res 137: 51-55(160)

Florin I, Rutberg L, Curvall M, Enzell CR (1980) Screening of tobacco smoke constituentsfor mutagenicity using the Ames'test. Toxicol 18: 219-232(161)

Crowley JP and Margard W (1978) Summary reports on determination of mutagenic/
carcinogenic and cytotoxic potential of four chemical compounds to Sherwin Williams
Company, unpublished data cited in EPA IRIS data base(162)

Gaikwad NW, and Bodell WJ (2001) Formation of DNA adducts by microsomal andperoxidase activation of p-cresol: role of quinone methide in DNA adduct formation. ChemBiol Interact 138: 217-229(163)

Hazleton Laboratories America Inc. (1989) Ivett JL. Dominant lethal assay in mice; pcresol. June 27, 1989 (at the request of CMA), EPA/OTS0529223(164)

Hazleton Labortories America, Inc. (1989) Seranau SC. Mutagenicity test on para-cresol
Drosophila Melanogaster sex-linked recessive lethal test. February 22, 1989 (at the requestof CMA).

(165)

Boutwell RK and Bosch DK (1959) The tumor-promoting action of phenol and related
compounds for mouse skin. Cancer Res 19: 413-424(166)

Hirose M, Inoue T, Asamoto M, Tagawa Y, Ito N (1986) Comparison of the effects of 13
phenolic compounds in induction of proliferative lesions of the forestomach and increase in
the labelling indices of the glandular stomach and urinary bladder of Syrian Golden
Hamsters. Carcinogenesis 7: 1285-1289(167)

Hazleton Laboratories America Inc. (1988) Mutagenicity tests on meta-cresol and paracresol in the in vitro transformation of BALB/C-3T3 cells assay, June 27, 1988 (at therequest of CMA), EPA/OTS 517694(168)

Bushy Run Centre (1989) Neeper-Bradley TL and Tyl RW. Two-generation reproduction
study of p-cresol (CAS No.106-44-5) administered by gavage to Sprague-Dawley (CD)rats. Project report 52-512. November 13, 1989. Unpublished data submitted by Bushy Run
Research Center to The American Chemistry Council Cresols Panel, Washington, DC,
EPA/OTS0529224(169)

Bushy Run Research Center/Hazleton Laoratories (1988) Project report 51-509,
Developmental toxicity evaluation of o-, m-, or p-cresol administered by gavage toSprague-Dawley (CD) rats, June,1988 (at the request of CMA) EPA/OTS0517695

UNEP PUBLICATIONS

293

OECD SIDS
6. REFERENCES

p-CRESOL
ID: 106-44-5
DATE: 24.05.2004(170)

Bushy Run Research Centre/Hazleton Laboratories (1988) Project Report 51-508,
Developmental toxicity evaluation of o-, m-, or p-cresol administered by gavage to New
Zealand White rabbits, June, 1988 (at the request of CMA) EPA/OTS0517695(171)

TRL (Toxicity Research Laboratories) (1986) TRL-Study #032-009: Subchronic
neurotoxicity study in rats of ortho-, meta- and para-Cresol, November 18, 1986 (at therequest of Research Triangle Instiute: Dietz, DD)(172)

Gleason MN, Gosselin RE, Hodge HC, Smith RP (1969) Clinical toxicology of commercial
products. Acute poisoning. third ed., The Williams & Wilkins Co., Baltimore, p. 42(173)

Bruce AM, Smith H, Watson AA (1976)Cresol poisoning. Med Sci Law 16: 171-176(174)

Cote MA, Lyonnais J, Lblond PF (1984) Acute Heinz body amnemia due to severe cresol
poisoning: successful treatment with erythrocytapheresis. Can. Med. Assoc J 130: 13191322(175)

DECOS (Dutch Expert Commitee on Occupational Standards)(1998) Cresols(o-, m-,p).
Health-based recommended occupational exposure limits 1998/27, health council of theNetherlands, Den Haag

(176)

Minami M. Katsumata M, Tomoda A (1990) Methemoglobinemia with oxidized hemoglobins
and modified hemoglobins found in bloods of workers handling aromatic compounds and in
those of a man who drank cresol solution. Biomed Biochim Acta 49: 327-333(177)

Lin CH and Yang JY (1992) Chemical burn with cresol intoxication and multiple organ
failure. Burns 18: 162-16(178)

Garrett JS: Association between bladder tumours and chronic exposure to cresol andcreosote. J. Occup. med 17, 492

294

UNEP PUBLICATIONSOECD SIDS

m- / p-CRESOL MIXTUREIUCLID
Data Set
Existing Chemical
CAS No.
EINECS Name

: ID: 15831-10-4: 15831-10-4: m-Cresol, compd. with p-cresol (2:1) (8CI)

Producer related part
Company
Creation date

: Bayer AG: 12.01.2001

Substance related part
Company
Creation date

: Bayer AG: 12.01.2001

StatusMemo:: ICCA m/p-Cresol mixture

Printing date
Revision date
Date of last update: 24.05.2004:: 24.05.2004

Number of pages: 87

Chapter (profile)
Reliability (profile)
Flags (profile): Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10: Reliability: without reliability, 1, 2, 3, 4
: Flags: without flag, non confidential, WGK (DE), TA-Luft (DE), Material
Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDSUNEP PUBLICATIONS

295

OECD SIDS
1. GENERAL INFORMATION

1.0.1

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

APPLICANT AND COMPANY INFORMATION

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
American Chemistry Council, Cresols Panel

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
ADCHEMCO Corporation

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Bayer Corporation

Flag
28.02.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
Street
Town

:
:
:
:
:
:

cooperating company
Concord Chemical Company

296

1300 Wilson Blvd.
22209 Arlington, VA
United States703-741-5629

Japan

100 Bayer Road
PA 15205-9741 Pittsburgh
United States

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:

United StatesFlag
28.02.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Dakota Gasification Company

Flag
28.02.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Honshu Chemical Industry Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
LaPorte (formerly Inspec Fine Chemicals, Inc.)

Flag
28.02.2001:

Critical study for SIDS endpoint

United States

Japan

United States

UNEP PUBLICATIONS

297

OECD SIDS
1. GENERAL INFORMATION

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Merisol (Merichem-Sasol USA LLC)

Flag
28.02.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Mitsui Chemicals, Inc.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Nippon Steel Chemical Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax

:
:
:
:
:
:
:
:
:

cooperating company
PMC Specialties Group, Inc.

298

United States

Japan

Japan

United States

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Telex
Cedex
Email
Homepage

:
:
:
:

Flag
28.02.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumikin Chemical Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Type
Name
Contact person
Date
StreetTown
Country
Phone
Telefax
Telex
Cedex
Email
Homepage

:
:
:
:
:
:
:
:
:
:
:
:
:

cooperating company
Sumitomo Chemical Company, Ltd.

Flag
31.05.2001:

Critical study for SIDS endpoint

Japan

Japan

1.0.2

LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR

1.0.3

IDENTITY OF RECIPIENTS

1.0.4

DETAILS ON CATEGORY/TEMPLATE

1.1.0

SUBSTANCE IDENTIFICATION

1.1.1

GENERAL SUBSTANCE INFORMATION

Purity type
Substance type::organic

UNEP PUBLICATIONS

299

OECD SIDS
1. GENERAL INFORMATION

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Physical status
PurityColour
Odour

:
:
:
:

liquidRemark
20.01.2003:

mixture of m-cresol (60-75%) and p-cresol (25-40%)

1.1.2

SPECTRA

1.2

SYNONYMS AND TRADENAMES

m-/p-cresol mixture
Flag20.01.2003:

Critical study for SIDS endpoint

Quantity:- tonnes produced in

Remark
Flag
28.05.2002::

128,000 t in 2001, estimated world capacity
Critical study for SIDS endpoint

LabellingSpecific limits
Symbols
Nota
R-Phrases

:
:
:
:
:

as in Directive 67/548/EEC

S-Phrases:

Remark
Flag
20.01.2003::

labelling for m- and p-Cresol
Critical study for SIDS endpoint::

as in Directive 67/548/EEC
corrosive

1.3

IMPURITIES

1.4

ADDITIVES

1.5

TOTAL QUANTITY

1.6.1

1.6.2

LABELLING

CLASSIFICATIONClassified
Class of danger

300

T, , ,,,(24/25) Toxic in contact with skin and if swallowed(34) Causes burns(36/37/39) Wear suitable protective clothing, gloves and eye/faceprotection(45) In case of accident or if you feel unwell, seek medical advice
immediately (show the label where possible)

UNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

R-Phrases
Specific limits::(34) Causes burns

Remark
20.01.2003:

classification for m- and p-Cresol

Classified
Class of danger
R-Phrases
Specific limits

:
:
:
:

as in Directive 67/548/EEC
toxic(24/25) Toxic in contact with skin and if swallowed

Remark
20.01.2003:

classification for m- and p-Cresol::

industrial
Chemical industry: used in synthesis

:
:

use
Intermediates

:
:

use
Solvents

1.6.3

PACKAGING

1.7

USE PATTERN

Type of use
Category
29.05.2002
Type of use
Category
29.05.2002
Type of use
Category
29.05.2002
1.7.1

DETAILED USE PATTERN

1.7.2

METHODS OF MANUFACTURE

1.8

REGULATORY MEASURES

1.8.1

OCCUPATIONAL EXPOSURE LIMIT VALUES

Type of limit
Limit value::

TLV (US)
5 other: ppm

Remark

:Flag
20.01.2003:

Skin notation. Critical effects: dermatitis, irritation,
CNS
Critical study for SIDS endpoint

Type of limit:(1)
TLV (US)UNEP PUBLICATIONS

301

OECD SIDS
1. GENERAL INFORMATION

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Limit value:

22 mg/m3

Remark

:Flag
21.03.2001:

Skin notation. Critical effects: dermatitis, irritation,
CNS.
Critical study for SIDS endpoint(2)

Type of limit: MAK (DE)
Limit value: 5 other: ppm
Short term exposure limit value
Limit value: 5 other: ppm
Time schedule:
Frequency: times
RemarkSourceFlag
27.05.2002:::

Risk of cutaneous absorption
TRGS 900 (DE)
Critical study for SIDS endpoint

Type of limit
Limit value::

MAK (DE)

Remark

:

MAK list Canc. cat 3ADanger of resorption through the skin.

27.05.2002(3)

Type of limit
Limit value::

MAC (NL)
22 mg/m3

Remark:Source:Grenswaarde voor blootstelling van korte duur:a) Numerieke waarde: onbekendb) Meeteenheid : onbekendc) Numerieke waarde: onbekendd) Tijdscheme: onbekende) Frequentie: onbekend
B.V. CONSOLCO Amsterdam
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

21.03.2001
Type of limit
Limit value::

MAK (DE)
22 mg/m3

Source:Atochem Paris la Defense
EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

07.06.1994(4)

Type of limit: MAK (DE)
Limit value: 22 mg/m3
Short term exposure limit value
Limit value: 22 mg/m3
Time schedule:
Frequency: times
RemarkSourceFlag
24.05.2002
1.8.2

302

:
:
:

danger of cutaneous absorption
TRGS 900 (DE)
Critical study for SIDS endpoint

ACCEPTABLE RESIDUES LEVELSUNEP PUBLICATIONSOECD SIDS
1. GENERAL INFORMATION
1.8.3

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

WATER POLLUTIONClassified byLabelled byClass of danger:::

other: Bayer AG
2 (water polluting)27.05.2002
1.8.4

MAJOR ACCIDENT HAZARDS

Legislation
Substance listed
No. in Seveso directive:::

Stoerfallverordnung (DE)Remark27.05.2002:

Annex I, No. 2

:
:
:
:

TA-Luft (DE)1.8.5

AIR POLLUTIONClassified byLabelled byNumberClass of danger

3.1.7 (organic substances)I

27.05.2002
1.8.6

LISTINGS E.G. CHEMICAL INVENTORIES

1.9.1

DEGRADATION/TRANSFORMATION PRODUCTS

1.9.2

COMPONENTS

1.10

SOURCE OF EXPOSURE

1.11

ADDITIONAL REMARKS

1.12

LAST LITERATURE SEARCH

Type of search
Chapters covered
Date of search:::Internal and External

Remark

:Toxicology: November 2002
Environmental aspects and ecotoxicology: January 2002
Search in external and internal databases, e.g. HSDB, Aquire, Biosis,
Embase, Toxline, Scisearch.

22.01.2003

UNEP PUBLICATIONS

303

OECD SIDS
1. GENERAL INFORMATION
1.13

304

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

REVIEWS

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA

2.1

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

MELTING POINT

Value
Sublimation
MethodYear
GLP
Test substance

:
:
:
:
:
:

other: no information supplied
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol (dried)

Flag
11.05.2004:

Critical study for SIDS endpoint

2.2

ca. 10 °C(5)

BOILING POINT

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

ca. 200 °C at

Flag
11.05.2004:

Critical study for SIDS endpoint

2.3

other: no information supplied
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol(5)

DENSITY

Type
Value
MethodYear
GLP
Test substance

:
:
:
:
:
:

densityca. 1.035 g/cm³ at 20 °C
other: no information supplied
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresolFlag
11.05.2004:

Critical study for SIDS endpoint
(5)

2.3.1

GRANULOMETRY

2.4

VAPOUR PRESSURE

Value
Decomposition
MethodYear
GLP
Test substance

:
:
:
:
:
:

Remark:Result:ca. 1 hPa at 20 °C
other (measured)
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol
static method, the measured value is presumably higher than the vapour
pressure for the m- and p-cresol isomers, because of the water content them/p-mixture which is not separated with the static method
vapour pressure for m- and p-cresol isomers = 0.147 hPaother results:

UNEP PUBLICATIONS305

OECD SIDS
2. PHYSICO-CHEMICAL DATA

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

ca. 6 hPa at 50 °C
ca. 8 hPa at 55 °C
11.05.2004
2.5

(5)

PARTITION COEFFICIENT

Partition coefficient
Log pow
pH value
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

Remark

:Flag
11.05.2004

:

2.6.1

1.94 - 1.96 at °C

no dataother TS: isolated cresol isomers
The log octanol-water partition coefficients of the cresol isomers range from
1.94-1.96
Critical study for SIDS endpoint(6)

SOLUBILITY IN DIFFERENT MEDIA

Solubility inValue
pH value
concentration
Temperature effects
Examine different pol.
pKa
Description
StableDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:

Water
24.4 g/l at °C
4.3
at °C

Remark
Flag
11.05.2004::

measured at room temperature
Critical study for SIDS endpoint

2.6.2

SURFACE TENSION

2.7

FLASH POINT

Value
Type
MethodYear
GLP
Test substanceat 25 °C

other: measured
2003
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol

(7)

:
:
:
:
:
:

ca. 86 °C
other: DIN 51758
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol

11.05.2004

306

(5)

UNEP PUBLICATIONSOECD SIDS
2. PHYSICO-CHEMICAL DATA
2.8

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

AUTO FLAMMABILITY

Value
MethodYear
GLP
Test substance

:
:
:
:
:

>= 500 °C atother: DIN 51794
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol

RemarkTest substance
11.05.2004::

Ignition temperature
63-75% m-cresol + 25-36% p-cresol
(5)

2.9

FLAMMABILITY

2.10

EXPLOSIVE PROPERTIES

Result:other: lower limit ca 1.1%, upper limit 7.6% by vol.

Test substance
22.10.2001:

63-75% m-cresol + 25-36% p-cresol
(5)

2.11

OXIDIZING PROPERTIES

2.12

DISSOCIATION CONSTANT

2.13

VISCOSITY

Test type
Test procedure
Value
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Capillary Method
DIN 53211
ca. 18.6 - mm2/s (static) at °C
other: DIN 53211
2001
no dataother TS: 63-75 % m-cresol + 25-36 % p-cresol

11.05.2004
2.14

(5)

ADDITIONAL REMARKSUNEP PUBLICATIONS307

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

3.1.1

PHOTODEGRADATION

TypeLight source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition:

Reliability:

Flag
12.05.2004:

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Result:Reliability:

Flag
11.05.2004:

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

308

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

air
nm
based on intensity of sunlightother (measured)
1995
no dataother TS: m-cresol, purity > 99 %Determination of the temperature-dependency of the
OH-radical reaction under simulated tropospheric conditions
With a OH radical concentration of 1 000 000 molec cm-3 anda temperature of 299 K, the half-life is 3.8 h
kOH = 5.17 x 10E-12 exp[(686+-231)/T] cm3 molec.-1 s-1 for atemperature range of 299-373 K
test substance concentration 0.05-5 ppm
reference compound (o-cresol) 0.05-2.3 ppm
radical source methylnitrite 1.5-11 ppm together with NOx
2-70 ppm(1) valid without restriction
Test procedure in accordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint
(8)
air
nm
based on intensity of sunlightother (measured): critical review
1994
no dataother TS: m-cresol, no purity reported
With a OH radical concentration of 1 000 000 molec/cm3, thehalf-life is 3.0 h at room temperature
K[OH] = 64 [10E-12 cm3 molecule-1 s-1]
K[NO3] = 9.74[10E-12 cm3 molecule-1 s-1]
K[O3] = 1.9 [10E-19 cm3 molecule-1 s-1]
(1) valid without restriction
Critical review, evaluation of all available experimental
data
Critical study for SIDS endpoint
(9)
air
nm
based on intensity of sunlightother (measured)
1990
no dataother TS: m-cresol, purity > 99 % (obtained from Aldrich Chemical
Company)

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Method:ResultReliability::

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

smog chamber experiment with black light irradiation
dry air pressure 735 Torr
Temp. 296+-2 K
irradiation time 4-20 min
reference substance: propene
OH radical concentration: (1-3) x 10E7 molecule cm-3
k[OH] = 67.8 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

11.05.2004

(10)

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:Result:Reliability

:

air
nm
based on intensity of sunlight1987
no dataother TS: m-cresol, no purity reported
I. Smog chamber experimentII. Inkrement methodm-cresol:I. observed: k[OH] = 57 [10E-12 cm3 molecule-1 s-1]
II. calculated: k[OH] = 94 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

12.05.2004

(11)

Type
Light source
Light spectrum
Relative intensity
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Method:ResultReliability

:
:

air
nm
based on intensity of sunlightother (measured)
1978
no dataother TS: m-cresol, no purity reported
smog chamber
Temp. 300 +-1 K
reference substances: n-butane, neopentane
initial concentration ca. 0.25 ppm for m-cresol
OH radical concentration: (1-4)x10E6 molecule cm-3
k[OH] = 67 [10E-12 cm3 molecule-1 s-1]
(1) valid without restriction
Test procedure in accordance with generally acceptedscientific standards; detailed documentation of test
procedure and test conditions

12.05.2004
Type
Light source
Light spectrum
Relative intensity(12) (13)
:
:
:
:

air
nm
based on intensity of sunlight

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Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

MethodResult::Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

1989
no dataother TS: m-cresol, no purity reported
No information on the method
K[OH] = 59 [10E-12 cm3 molecule-1 s-1]
t[1/2] = 0.3 d(4) not assignablesecondary literature

11.05.2004(14)

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result
Test condition
Reliability:::

other (measured)
1985
no dataother TS: m-cresol, no purity reported, but in most cases purity exceeded
98 %substance adsorbed onto silica gel (100 ng/g)
irradiated with UV lamp (290 nm) in a microphotoreactor
degradation 33.3% of applied amount
17 h at 15 degrees C(3) invalid
Unsuitable test system

12.05.2004
3.1.2

(15)

STABILITY IN WATER

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Remark:Reliability:

Flag
11.02.2003

:

3.1.3

Based on the chemical structure of the compound hydrolysis
is not expected under temperature and pH values occuring in
the environment.
(2) valid with restrictions
Expert judgement
Critical study for SIDS endpoint

STABILITY IN SOIL

TypeRadiolabel
Concentration
Soil temperature
Soil humidity
Soil classification
Year
Deg. product
MethodYear
GLP
Test substance

310

other TS: m-cresol

:
:
:
:
:
:
:
:
:
:
:
:

laboratory
°C

1990
no
other TS: m-cresol

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Method:Result:

Test condition:

Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Bench-scale experiments with contaminated soil.
Determination of passive evaporation and biodegradation ofcresolspassive evaporation half-life 4.2 - 4.8 weeks
biodegradation: after 4 days below detection limit
Passive evaporation: plastic petri plates (88x18 mm) placedon canopy-covered table. Temp. 10-17 degrees C, humidity 75%
Shake-flask biodegradation test: 8-25 g soil mixed with 50
ml buffer solution; shaken for 4 days
(3) invalid
Methodological deficiencies

11.02.2003

(16)

Type
Radiolabel
Concentration
Soil temperature
Soil humidity
Soil classification
Year
Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

Method:Remark:Result:Reliability:

laboratory
yes°Cother: see Method below
1985
noother TS: m-cresol
Inocolum: subsurface microbial community of a pristine
aquifer (Lula, Okla.)
Soil: aquifer solid sample, unconsilated sand, from a depthof 4.5-5.6 m below surface
All substances were radiolabeled.
Incubation period: 8 months
Determination of mineralization via 14CO2 evolution
The highest percent biodegradation achieved for nearly all
the substances tested was 35% (e.g. anilin, which is thestandard reference substance for all ready tests in OECD 301
achieved after 100 days only 15% biodegradation).
- After 160 days and at a concentration of 39 ng/g m-cresolin soil, ca.15% mineralization was observed.
- The percent mineralized increased slowly and linearly withtime.
- For the majority of the test compounds no adaptation
period was observed.
(3) invalid
No standard test procedure. Test design can only be used toassess degradation in soil of the pristine aquifer of Lula,
Okla.

11.02.2003
3.2.1

(17)

MONITORING DATA

Type of measurement
Media
Concentration
Method::::other: contamination at a special working place

Remark:Combined m-/p-cresol isomers were detected among otherchemicals in the indoor air at a shale oil wastewater
facility at a concentration of 5.1 ppb.

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Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(2) valid with restrictions
Basic data given

20.01.2003

(18)

3.2.2

FIELD STUDIES

3.3.1

TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

volatility
water - air% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: measured
1999

Method:Result:

Test condition:

Reliability:

Flag
12.05.2004:

Thermodynamic column method of Brunner et al. 1990 applied [Brunner S,
Hornung E, Santl H, Wolff E, Pringer OG, Altschuh J, Brueggemann R(1990) Henry´s law constants for polychlorinated biphenyls: Experimental
determination and structure-property relationship. Environ Sci Technol 24,
1751 - 1754]:- Aqueous solution of the TS produced in a generator column- Solution is passed through gas liquid desorption column where it contacts
a gas stream and the partition equilibrium is reached- Gas and water are separated: water flows to the receiver dosing funnel,
the gas is conducted into an absorption vessel where the TS is absorbed inorganic solvent
Henry's law constant (25 degrees C) for m-cresol:
H = 3.5 E-5 calculated to
H = 8.67 E-2 Pa.m3.mol-1- Temperature 25 °C- Gas phase: Nitrogen- Liquid phase: Demineralized, distilled water- Analysis: GC/ECD(2) valid with restrictions
basic data given
Critical study for SIDS endpoint
(19)

Type
Media
Air
Water
Soil
Biota
Soil
Method
Year

:
:
:
:
:
:
:
:
:

adsorption
water - soil
% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level I)% (Fugacity Model Level II/III)% (Fugacity Model Level II/III)other: batch equilibrium method similar to OECD Guideline 106
1982

RemarkResult
Test condition:::

Koc value was determined for clay loam soil
Koc=34.58 for m-cresol
Test substance: m-cresol
Soil: Brookston clay loam soil, collected from top 15 cm,
air-dried, 5.10 % organic matter, pH 5.7
soil/solution ratio 1:10
TS concentrations 5, 10, 20, 30, 50 mg/l, deoxygenated by

312

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3. ENVIRONMENTAL FATE AND PATHWAYS

Reliability:

Flag
12.05.2004

:

3.3.2

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

purging with N2
triplicate samples, temp. 20+-1 degrees C, incubation period 24 h(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with general accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint(20)

DISTRIBUTION

Media
MethodYear:::

air - biota - sediment(s) - soil - waterCalculation according Mackay, Level I
2001

Result:

Test condition:

Calculation for m-cresol:
Calculated distribution between environmental compartments:
Air:
2.33 %
water:
96.32 %
soil:
0.69 %
bottom sediment: 0.65 %suspended sediment: 0.001 %biota:
0.0004 %data used in calculation
temperature (°C):
25molar mass (g/mol): 108.14
vapor pressure (Pa): 14.7
water solubility (g/l): 22.7
log Kow:
1.96

Reliability:

Flag
11.02.2003:

volumes in unit world (m3)air:
6 000 000 000
water:
7 000 000
soil:
45 000sediment:
21 000susp. sediment:
35
biota (fish):7(2) valid with restrictions
generally accepted calculation method
Critical study for SIDS endpoint
(21)

3.4

MODE OF DEGRADATION IN ACTUAL USE

3.5

BIODEGRADATION

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

aerobic
predominantly domestic sewage.8 mg/l related to COD (Chemical Oxygen Demand)
related to= 90 (±) % after 28 day(s)readily biodegradable
7 day(s) = 45 - 80 %14 day(s) = 70 - 90 %21 day(s) = 75 - 70 %28 day(s) = 90 - 90 %UNEP PUBLICATIONS

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Control substance
Kinetic::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Result
Test condition::

Reliability:

Flag
12.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Control substance
Kinetic::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Remark:Result:

Test condition:314

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004%
other: phenol, 0.8 mg/l
28 day(s) = 73 %%OECD Guide-line 301 D "Ready Biodegradability: Closed Bottle Test"
1988
noother TS: m-cresol pure
10-day window criteria is met
Inoculum- Type of sludge: activated sludge- Source: treatment plant, receiving domestic sewage- Sampling site: Odenthal
Concentration of control substance: 0.8 mg/l
Analytical parameter: Oxygen consumption
Test temperature: 20 degrees C
Test was performed in two paralleles.
(2) valid with restrictions
Guideline Study
Critical study for SIDS endpoint(22)
aerobic
predominantly domestic sewage
2.4 mg/l related to COD (Chemical Oxygen Demand)
related to= 65 (±) % after 28 day(s)7 day(s) = 55 - 58 %14 day(s) = 58 - 66 %21 day(s) = 61 - 65 %28 day(s) = 65 - 65 %%other: phenol, 2.4 mg/l
28 day(s) = 69 %%OECD Guide-line 301 D "Ready Biodegradability: Closed Bottle Test"
1988
noother TS: m-cresol pure
In two further tested concentrations (8 and 24 mg/l) the
dissolved oxygen was completely emaciated within 7 days(concentration of control substance 8 and 24 mg/l for tests
with 8 and 24 mg/l of test substance, respectively. Also i nthese control experiments, oxygen was emaciated).
Compared to the test with 0.8 mg/l the extent of degradationis lesser at 2.4 mg/l presumably due to the fact that mostof the oxygen was used up at the high test substanceconcentration
Inoculum / test organism- Type of sludge: activated sludge- Source: treatment plant, receiving domestic sewage- Sampling site: Odenthal
Concentration of control substance: 2.4 mg/l
Analytical parameter: Oxygen consumption
Test temperature: 20 degrees C

UNEP PUBLICATIONSOECD SIDS
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Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Test was performed in two paralleles.
(2) valid with restrictions
Guideline Study

12.05.2004

(22)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition:

Reliability:

Flag
12.05.2004:

Type
Inoculum
Contact time
Degradation
ResultDeg. product
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::aerobic
activated sludge, domestic
100 mg/l related to Test substance
related to
80 - 95 (±) % after 40 day(s)other: comparable to OECD Guide-line 301 C
1981
noother TS: m-cresol, purity > 99 %Initial sludge concentration: 30 mg d.w./l; aniline asreference compound
Incubation period: 20-40 days; no oxygen uptake curve given;degradation of reference substance aniline >/= 60 % within
28 daysThe oxygen uptake curves are not reported. However, the authors statethat all test compounds revealed the lag phase, biodegradation phase andthe plateau region within a period of 10 days, indicating that the 10-day
window criteria is met.
First order biodegradation constant (hr-1): ln k = -5.77
maximum specific substrate uptake rate per unit biomass km = 17.3 / day(Aniline 16.1, Phenol 16.9).
m-Cresol is slightly better biodegradable than phenol and aniline.
Inoculum /test organism- Type of sludge: activated- Source: municipal treatment plant, receiving predominantly
domestic sewage- Initial cell concentration: 30 mg/l
Test system- Culturing apparatus: Sapromat- Closed vessels used: yes
Initial test substance concentration: 100 mg/l
Duration of the test: 20-40 days
Test conditions- Composition of synthetic medium: OECD
- Test temperature: 25 degrees C
Reference substance: aniline 100 mg/l(2) valid with restrictions
study comparable to OECD Guideline 301 C
Critical study for SIDS endpoint(23)
aerobic
activated sludge, industrial
96 (±) % after 10 day(s)OECD Guide-line 302 B "Inherent biodegradability: Modified Zahn-Wellens
Test"
1990
no dataother TS: m-cresol, no purity reported

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m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Result
Test condition::

Reliability:

Flag
24.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Method:Result
Test condition::

Reliability:

Flag
24.05.2004:

Type
InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:

anaerobic
anaerobic sludgeyes

Method:Result:primary anaerobic sludge from 12 treatment plants receiving
mainly domestic wastewater were diluted to
10 % in a mineral salts medium, test substanceconcentration: 30 mg/l; secondary anaerobic sludge from 2
treatment plants diluted to 10 % in a mineral salts medium,
test substance: 50 mg/l;
incubation for 8 weeks; triplicate samples
primary sludges:
no degradation was observed in 4 sludges; degradation ranged
from 55 to 103 % in 6 sludges (lag times for approx 20 % of
theoretical CH4 production: 4-6 weeks); insufficient datafor 2 sludges.
secondary sludge:
degradation was 92% after 4 weeks with the first sludge and316

90% degradation during the log-phase (8 days)
Test substance conc. 50-400 mg/l DOC, 200-1000 mg/l COD
acclimatization phase 2 days(2) valid with restrictions
Guideline study; basic data given
Critical study for SIDS endpoint(24)
aerobic
activated sludge, adapted
200 mg/l related to COD (Chemical Oxygen Demand)
related to95.5 (±) % after 5 day(s)other: batch system (similar to OECD 302B "Zahn-Wellens Test")
1976
noother TS: m-cresol, no purity reported- Test compound was sole source of carbon- Inoculum density: 100 mg dry matter/l; gradual increase of
TS concentration during 20 days adaptation period- With volatile substances a test without inocculum was done
to differentiate the actual biological degradation from thelosses due to mere volatilization
Initial degradation rate: 55.0 mg COD/g/h
20 +- 3 degrees C; pH 7.2; mineral salts medium; dark;
continuously stirred(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
basic data given
Critical study for SIDS endpoint
(25)

1981
no
other TS: m-cresol, no purity reported
74-82-8 200-812-7 methane

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Test condition:

Reliability:

Flag
12.05.2004:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Method:Remark:Result:

Test condition
Reliability

:
:

Flag
12.05.2004:

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

90% after 5 weeks with the second (degradation related totheoretical methane and CO2 production)
35 degrees C, due to storage of sludges before incubation,
lag phase of methanogenesis could be increased in somesludges(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(26)
anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
56 day(s)(±) % after
yes
1984
no
other TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
primary and secondary anaerobic sewage sludge from 9
treatment plants diluted to 10 % in a mineral salts medium;
degradation measured as gas pressure increase
data have been published by the authors as a NTIS-study(previous data set)in 2 different secondary sludges >75% degradationin 9 different primary sludges degradation 0-103%
incubation for 8 w at 35 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint(27)
anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related to
yes
1988
no
other TS: m-cresol, no purity given (obtained from Aldrich Chemicals)
74-82-8 200-812-7 methane
primary anaerobic digesting sludge receiving a mixture ofdomestic and industrial wastewaterlag time 40 days, accompanied with inhibition of gas
production
net total gas production was 75 % +/- 15 % of thetheoretical production (CH4+CO2)- medium 2-3 g dw/l sludge- incubation for >= 60 d at 35 degrees C- 3 replicates

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Reliability:

Flag
11.02.2003:

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Remark:Result:Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004- sterile controls for abiotic gas production- gas production measured with hand-held pressure meter(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetailCritical study for SIDS endpoint(28)

24.05.2004
Type
Inoculum::

Concentration:

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

ResultReliability::

aerobic
activated sludge, domestic.05 mg/l related to Test substance
related to35.6 (±) % after 5 day(s)other: Activated sludge test
1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given
The bioaccumulation factor of the substance and its
metabolites in activated sludge was 1100
The readily biodegradable compounds methanol and phenol were about
equally degraded like m-Cresol (41, 37 and 36 %)(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail
(15)
aerobic
other bacteria: acclimatized mixed culture of pentachlorophenol-degrading
bacteria
5 mg/l related to Test substance
related to
29 day(s)(±) % after
38 hour(s) 50 %46 hour(s) 90 %%%%other: Die-away Test
1990
noother TS: m-cresol, gas chromatographic grade
no lag phase(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail24.05.2004
Type
Inoculum

318

(29)
:
:

aerobic
other: denitrifying cultures from unadapted mixed wastewater

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
Concentration:

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Result
Test condition::

Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004.39 mg/l related to Test substance
related to
100 (±) % after 17 day(s)other: measured
1989
noother TS: m-cresol, no purity reported
lag phase 3 days, completely degraded in 17 d
inoculum prepared by mixing waste water samples from 12
denitrifying treatment plants
incubated at 27 degrees C in the dark(2) valid with restrictions
Study in accordance with generally accepted scientificstandards and described in sufficient detail24.05.2004

(30)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Result:

Test condition:

Reliability:

anaerobic
other: municipal sewage sludge from primary anaerobic digesters
50 mg/l related to Test substance
related to
56 day(s)100 (±) % after 49 day(s)yesother: measured
1983
noother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
substance disappeared completely after 7 weeks
net CH4 production >90% of theoretical value
no transformation products observed
mineral salt medium with 10% sludge
Temperature 35 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(31)

Type
InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:

anaerobic
anaerobic sludgeyesother: measured
1983
noother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane

Remark:Result:sensitivity of acid formers and methanogenic consortia
examined
at <= 400 mg/l, m-cresol was not fermented andshowed no inhibition of methane formation from degradable
substrates as compared to control cultures; 1000 mg/l
inhibited the methane production significantly (60 % ofcontrol values)

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Test condition:

Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

screening optimized for mechanistic study
m-cresol concentration: 200, 400 or 1000 mg/l
incubation for 6 w at 37 degrees C(4) not assignable
No standard test procedure, but in accordance with generally
accepted scientific standards; not relevant for purpose of
HPV program

12.05.2004

(32)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Deg. products:

Result:

Test condition:

Test substance
Reliability::

anaerobic
other: anaerobic sludge, adapted
300 mg/l related to Test substance
related toyesother: see test condition
1986
noother TS: m-cresol, no purity reported (Aldrich chemicals) (methyl 14Clabelled from Pathfinder Lab.)74-82-8 200-812-7 methane
Degradation: ca. 100 % after 9 days
Most of the methyl carbon of m-cresol (87 %) was converted
to CH4.
preincubation for 2-3 months
incubation for 20 d at 37 degrees C
14C-methyl labeled(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(33)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

anaerobic
anaerobic sludge
50 mg/l related to DOC (Dissolved Organic Carbon)
related toyesother: measured
1982
noother TS: m-cresol, purity > 95 %
74-82-8 200-812-7 methane- Sludge from 2 municipal plants- Methane production monitored- HPLC to monitor disappearance of substratemineralization (related to theoretical methane and CO2
production) was 92% after 4 weeks with the first sludge and
90% after 5 weeks with the second
incubation at 35 degrees C in the dark, 10 % sludge
inoculum, duplicate tests(2) valid with restrictions
No standard test procedure, but in accordance with generally acceptedscientific standards and described in sufficient detail12.05.2004
Type
Inoculum
Concentration

320

(34)
:
:
:

anaerobic
other: anoxic lake sediment.1 mg/l related to Test substance.8 mg/l related to Test substance

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

yes
other: measured
1982
noother TS: m-cresol, purity > 95 %
74-82-8 200-812-7 methane

Result
Test condition::

Reliability:

after 29 weeks no significant CH4 or CO2 formation observed
incubation at 20 degrees C in the dark with occasional
shaking(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(34)

Type
Inoculum::

Concentration:

Contact time
Degradation
ResultKinetic of testsubst.

:
:
:
:

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Reliability:

anaerobic
other bacteria: acclimatized mixed culture of pentachlorophenol-degrading
bacteria
5 mg/l related to Test substance
related to
29 day(s)(±) % after
144 hour(s) 10 %197 hour(s) 50 %236 hour(s) 90 %%%other: Die-away Test
1990
noother TS: m-cresol, gas chromatographic grade(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail11.02.2003

(29)

Type
Inoculum
Concentration:::

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:
:

Result:

Test condition:

Reliability:

anaerobic
other: phenol-enriched methanogenic culture
100 mg/l related to Test substance
related to
100 (±) % after 58 day(s)yesother: measured
1988
noother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
lag time 42 d, complete disappearance after 58 d,
the CH4 production was 85 % of the theoretical production
nominal test concentrations m-cresol 50, 100, 150, 250, 300,
400, 500, and 700 mg/l + phenol 200 mg/l
incubation at 35 °C with continuous shaking(2) valid with restrictions

UNEP PUBLICATIONS321OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(35)

Type
InoculumDeg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:
:
:

anaerobic
other: shallow anaerobic alluvial sand aquifer
yesother: measured
1986
noother TS: m-cresol, no purity reported (obtained from Aldrich Chemical Co.)
74-82-8 200-812-7 methane

Method:Result:

Test condition:

Reliability:

2 sampling sites: 1 methanogenic, 1 sulfate-reducing
both aquifers receive leachate from a municipal landfill
lag time 43 days under sulfate-reducing and 46-90 days undermethanogenic conditions, no data for complete degradation
given
test medium: 50 g [wet weight] of aquifer solids and 50 ml
of groundwater
incubation at room temperature in the dark, quadruplicates
preincubation 5 days, addition of 150 to 200 µM test
substance(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(36)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Method:Result:

Test condition:

Reliability:

anaerobic
other: undefined methanogenic consortia from river sediment
54 mg/l related to Test substance
related toyesother: measured
1989
noother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
black anoxic mud collected from a river inoculated in amineral medium (10% w/v)
non-acclimated consortia: turnover rate 1.10 µmol/day/g
sediment dw (lag-phase 16 d)
acclimated consortia: turnover rate 2.37 µmol/day/g sedimentdw (lag-phase 0 d, based on a 24-days-incubation period),
the CH4 production was 96 % of the theoretically possible
yield
incubation at 28 degrees C in the dark
cultures were refed with 60 mg/l test substance every 2-4 w
for a total of 18 months(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004
Type
Inoculum
Concentration

322

(37)
:
:
:

aerobic
10 mg/l related to Test substance

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Contact time
Degradation
ResultDeg. product
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Result:Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

related to
3 day(s)26 - 100 (±) % after 3 day(s)other: cultivation method
1987
no dataother TS: m-cresol, no purity reported in abstract
biodegradation in river water = 100 %biodegradation in sea water = 26 %The authors assume the compound to be moderately to easily
biodegradable(4) not assignable
Japanese reference with short abstract in English

12.05.2004

(38)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substanceDeg. products

:
:
:
:
:
:

Result:

Test condition
Reliability::

anaerobic
other: microcosm containing aquifer and ground water
18 mg/l related to Test substance
related toyesother: measured
1989
no dataother TS: m-cresol, no purity reported
74-82-8 200-812-7 methane
lag time 110 days, disappearance after approx. 225 d (values
taken from a graphics)
methanogenic conditions in a microcosm(3) invalid
Insufficient documentation

12.05.2004

(39)

Type
Inoculum
Concentration:::

Deg. product
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result:Reliability:

anaerobic
other: anoxic aquifer
300 µmol/l related to Test substance
related toother: measured
1990
no dataother TS: m-cresol, no purity reported
anoxic aquifer slurries held under sulfate- andnitrate-reducing conditions
m-cresol was largely degraded in less than 6 ddegradation dependant on sulfate, inhibited by 1.0 mM
molybdate, not influenced by bromoethanesulfonic acid(4) not assignable
only abstract available

12.05.2004
3.6

(40)

BOD5, COD OR BOD5/COD RATIOUNEP PUBLICATIONS

323

OECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS
3.7

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

BIOACCUMULATION

Species
Exposure period
Concentration
BCF
Elimination
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Leuciscus idus melanotus (Fish, fresh water)
3 day(s) at °C.05 mg/l
20
no dataother: measured
1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given

Remark:Test condition:

Reliability:

Flag
12.05.2004:

Determination of radioactivity includes possible metabolized and/or
incorporated intermediates
The authors report BCF in different tables to be 17 or 20
5 fish (2-4 g) were exposed to m-cresol in a closed system andconcentrations were determined by following radioactivity in fish and water;
BCF values related to wet weight; 20-25 degrees C; pH 7; hardness 100
mg CaO/l(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetailCritical study for SIDS endpoint(15)

Species
Exposure period
Concentration
Elimination
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

other: Chlorella fusca (algae)
24 hour(s) at °C.05 mg/l
no dataother: measured
1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given

Remark:In this study BCF-values of 40 and 4,900 for algae arereported without explanation for the difference.

Test condition
Reliability::

It is a common observation that test substance adsorbes atthe surface of the algae. Due to the high surface / volume
ratio a high BCF could be obtained.
20-25 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004
Species
Exposure period
Concentration
BCF
Elimination
MethodYear
GLP
Test substance

324

(15)
:
:
:
:
:
:
:
:
:

other: Activated Sludge
5 day(s) at °C
1100
other: measured
1985
noother TS: 14C-labelled m-cresol presumably > 98 % purity; no specificactivity given

UNEP PUBLICATIONSOECD SIDS
3. ENVIRONMENTAL FATE AND PATHWAYS

Remark:Reliability:

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Values of bioaccumulation factors range from 10 up to
42,800.
Esters and higher alcohols are placed in the intermediate
range between 3,000 and 5,000. Sodium acetat with anaccumulation factor of 29,100 is remarkable. In this ranking
m-Cresol belongs to the group of compounds with low
accumulation potential.
Correlation between accumulation factors andphysico-chemical parameters was not practicable.
(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail.

12.05.2004
3.8

(15)

ADDITIONAL REMARKS

Memo

:

biodegradation under anaerobic conditions

Method:Result:

Test substance:

Reliability:

enrichment cultures prepared by addition of 3 g/l m-cresol
once per week
initial concentration 200-300 mg/l test substanceincubation at 37 degrees C in the dark
1st step: incorporation of CO2 giving
4-hydroxy-2-methylbenzoic acid
2nd step:
2a: dehydroxylation to 2 methylbenzoic acid (not further
metabolized) to a minor degree
2b: ring reduction, ring fission and beta-oxidation toacetate. Ring reduction appeared to be the rate-limiting
step, because no subsequent intermediates accumulated
1. U-ring-14C m-cresol
2. methyl-14C m-cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail11.12.2002(41)

UNEP PUBLICATIONS

325

OECD SIDS
4. ECOTOXICITY

4.1

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

ACUTE/PROLONGED TOXICITY TO FISH

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

MethodResult::

Test condition:

Reliability:

Flag
12.05.2004:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

MethodResult::

Test condition:326

flow throughOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
8.9
yes
other: US EPA, Methods for acute toxicity tests with fish,
macroinvertebrates, and amphibians. Nat. Environm. Res. Center, Corvallis(1974)
1980
no dataother TS: m-cresol, no purity reported
Mean length/mean weight of fish: 7.9 cm/6.0 g
sublethal effects: hyperactivity, rapid operculation,
sensitive to disturbance and gathering at the surface
DILUTION WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- Conductance: 1212.3 µmhos/cm at 25 degrees C
TEST SYSTEM- Concentrations: 1:2 dilution series- Number of replicates: 2- fish per replicate: 10- Test temperature: 14 degrees C- Dissolved oxygen: 6.5 mg/l (84.5% of saturation)- pH: 8.1
- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(42)
flow throughPimephales promelas (Fish, fresh water)
96 hour(s)
mg/l
55.9
yes
other: US EPA, Methods for acute toxicity tests with fish,
macroinvertebrates, and amphibians. Nat. Environm. Res. Center, Corvallis(1974)
1980
no dataother TS: m-cresol
Mean length/mean weight of fish: 4.9 cm/1.6 g
sublethal effects: loss of equilibrium, erratic swiming andtwitching at a test substance concentration of 49.8 mg/l
DILUTION WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- Conductance: 1212.3 µmhos/cm at 25 degrees C

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004
TEST SYSTEM- Concentrations: 1:2 dilution series- Number of replicates: 2- fish per replicate: 10- Test temperature: 14 degrees C- Dissolved oxygen: 6.5 mg/l (84.5% of saturation)- pH: 8.1
- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint

Reliability:

Flag
11.02.2003:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticSalmo trutta (Fish, fresh water, marine)
96 hour(s)
mg/l
= 8.4

Method:Result:

Test condition
Reliability

:
:

Flag
12.05.2004:

10 acclimated fish exposed per concentration, 20 served ascontrols.
LC50 (6 h) = 11.0 mg/l
LC50 (24 h) = 8.6 mg/l
LC50 (48 h) = 8.4 mg/l
12 degree C, reconstituted water(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticSalvelinus fontinalis (Fish, estuary, fresh water)
96 hour(s)
mg/l
= 7.6

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrols.
LC50 (6 h) = 11.4 mg/l
LC50 (24 h) = 8.2 mg/l
LC50 (48 h) = 7.6 mg/l
at concentrations of 6 to 20 mg/l, the approximate
incidences of surfacing were 20 %12 degree C, reconstituted water(2) valid with restrictions

(42)

no
1969
no
other TS: m-cresol, reported to be "purified grade"

(43)

no
1969
no
other TS: m-cresol, reported to be "purified grade"

UNEP PUBLICATIONS

327

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

Flag
12.05.2004:

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticOncorhynchus mykiss (Fish, fresh water)
96 hour(s)
mg/l
= 8.6

Method:Result:

Test condition
Reliability::

10 acclimated fish exposed per concentration, 20 served ascontrols.
LC50 (6 h) = 14.9 mg/l
LC50 (24 h) = 10.4 mg/l
LC50 (48 h) = 10.2 mg/l
In an additional test under flow-through conditions aconcentration of 10 mg/l caused total incapacitation in 15
of 20 fish within 11.5 min, after which a recovery to ahigher level of activity was observed
12 degree C, reconstituted water(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

(43)

no
1969
no
other TS: m-cresol, reported to be "purified grade"

12.05.2004

(43)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

semistatic
Poecilia reticulata (Fish, fresh water)
96 hour(s)
mg/l
23.12

MethodTest condition
Reliability:::

80 % of the test solution renewed at 12 h intervals
25-27 degrees Celsius, pH 7(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

no
1982
no
other TS: m-cresol, purity 99 % (BDH Chemicals)

12.05.2004
Type
Species
Exposure period
Unit
LC0
LC50
LC100

328

(44)
:
:
:
:
:
:
:

staticBrachydanio rerio (Fish, fresh water)
96 hour(s)
mg/l
11
15.9
22

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:

Test condition
Reliability::noother: Pruefrichtlinie UBA (summer 1980)1982
no dataother TS: m-cresol, no purity reported
pH 7.5 +- 0.3(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

12.05.2004

(45)

Type
Species
Exposure period
Unit
EC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticGadus morrhua (Fish, fresh water)
96 hour(s)
mg/l
> 30

Method:Result:

Test condition
Reliability::

effect endpoints: death, pathology, inhibition of cleavage
and differentiation, pigment defects
parallel test with larvae (6 days after hatching) showed
pigment effects at 10 and 30 mg/l
5 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

yes
1985
no
other TS: m-cresol, purity > 98 % as determined by GC (obtained from
Merck)

12.05.2004

(46)

Type
Species
Exposure period
Unit
LC0
LC50
LC100
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)
mg/l
10
17
22
no
other: Test procedure of the Abwasserabgabengesetzentwurf (Deutscher
Bundestag 1974)1982
noother TS: m-cresol, no purity reported(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

12.05.2004
Type
Species(47)::

Cyprinus carpio (Fish, fresh water)

UNEP PUBLICATIONS

329

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:

24 hour(s)mg/l25Remark:Reliability:

results from: Albersmayer and Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analyticalmonitoring, no information about the test substance. Further
details are missing

1959
other TS: m-cresol

11.02.2003

(48)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

Rutilus rutilus (Fish, fresh water)
24 hour(s)
mg/l
23
1959
other TS: m-cresol, no purity reported
results from: Albersmayer and Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analyticalmonitoring, no information about the test substance. Further
details are missing

12.05.2004

(48)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Remark:Reliability:

Tinca tinca (Fish, fresh water)
24 hour(s)
mg/l
21
1959
other TS: m-cresol, no purity reported
results from: Albersmayer and Erichsen: Z. Fisch. 8 (1/3),
29-66 (1959)(3) invalid
Study does not follow any guideline. No analyticalmonitoring, no information about the test substance. Further
details are missing

12.05.2004
Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring

330

(48)
:
:
:
:
:
:
:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)
mg/l
6
no

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Method:Year
GLP
Test substance:::

Reliability:

other: Mann, H., Fischtest mit Goldorfen zur vergleichenden Pruefung derakuten Toxizitaet von Wasserinhaltsstoffen und Abwaessern, Praktische
Erfahrungen aus 3 Ringtesten, Z. f. Wasser- u. Abwasser-Forschung 9,103-109 (1976)1978
noother TS: m-cresol, no purity reported(4) not assignable
Secondary literature not available (Mann 1976)

12.05.2004

(49)

Type
Species
Exposure period
Unit
LC50
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

staticother: Pleuronectes sp. (plaice)48 hour(s)mg/l
10 - 33

Test condition
Test substance
Reliability:::

15 degrees C
cresol (isomer not specified)(4) not assignablesecondary literature

no
1971
no
other TS: cresol, isomer not specified

12.05.2004

(50)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

Lepomis macrochirus (Fish, fresh water)
96 hour(s)mg/l
10 - 13.6
1971
other TS: m-cresol, no puritiy reported(4) not assignablesecondary literature

12.05.2004

(51)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

Oryzias latipes (Fish, fresh water)
48 hour(s)
mg/l
24
1986
other TS: m-cresol, no puritiy reported(4) not assignablesecondary literature, original source unknown

12.05.2004
Type
Species
Exposure period

(52)
:
:
:

staticLeuciscus idus (Fish, fresh water)
48 hour(s)UNEP PUBLICATIONS331OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Unit
LC0
LC50
LC100
Limit test
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability

:

mg/l
10
17 - 19
21 - 26
noother: Bestimmung der Wirkung von Wasserinhaltsstoffen auf Fische. DEV,
L 15 (1976)1978
noother TS: m-cresol, no purity reported(4) not assignable
Insufficient documentation

12.05.2004

(53)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

other: Agonus cataphractus (poacher)48 hour(s)mg/l
10 - 33
1960
other TS: m-cresol(4) not assignablereference not available

11.02.2003
4.2

(54)

ACUTE TOXICITY TO AQUATIC INVERTEBRATESTypeSpecies
Exposure period
Unit
EC0
EC50
EC100
Analytical monitoring
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

Method:Result
Test condition::

Reliability:

Flag
12.05.2004:

Type
Species::332

staticDaphnia magna (Crustacea)
24 hour(s)
mg/l
13
25
50
no
other: immobilisation test according to Bringmann & Kühn: Z. Wasser
Abwasser Forsch. 10, 162-166 (1977)1982
noother TS: m-cresol, no purity reported
Exposure of 24 h old Daphnia (strain IRCHA); 10 individuals
per concentration, duplicate samples
effect values refer to nominal test substance concentrations
20 degrees C; initial pH 8.0 +/-0.2; water saturated withoxygen; hardness: 16° d.h. (corresponding to 286 mg CaCO3/l)(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(55)
flow through
Daphnia pulicaria (Crustacea)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Exposure period
Unit
LC50
Analytical monitoring
Method

:
:
:
:
:

Year
GLP
Test substance:::

Test condition:

Reliability:

Flag
12.05.2004:

Type
Species
Exposure period
Unit
EC0
EC50
EC100
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

RemarkTest condition::

Reliability:

Flag
12.05.2004:

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

48 hour(s)mg/l> 99.5yesother: US EPA, Methods for acute toxicity test with fish,
macroinvertebrates, and amphibians. Nat. Environm. Res. Center, Corvallis(1974)
1980
noother TS: m-cresol, no purity reported
DILUTION AND TEST WATER- Source: well water- Hardness: 707.3 mg CaCO3/l- pH: 8.1
- Oxygen content: 6.5 mg/l (84.5% of saturation)- Conductance: 1212.3 µhos/cm at 25 degrees C- Number of replicates, individuals per replicate: 10- Test temperature: 14 +- 1 degrees C- Photoperiod: 16 h light, 8 h dark
(1) valid without restriction
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
detailed documentation of test procedure and test conditions
Critical study for SIDS endpoint(42)
Daphnia magna (Crustacea)
24 hour(s)
mg/l
1.6
8.9
25
no
1977
no
other TS: m-cresol, no purity reported
Effect endpoint: immobilisation
Hardness 16 degrees (German), pH 7.6-7.7, 20-22 degrees
Celsius(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint(56)
Daphnia magna (Crustacea)
24 hour(s)
mg/l
19.2
no
other: AFNOR (1974)1987
no dataother TS: m-cresol, purity > 95 %UNEP PUBLICATIONS333

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

RemarkTest condition::

Reliability:

Effect endpoint: immobilisation
Reconstituted hard water 200 mg/l CaCO3
pH 7.8-8.2
dissolved oxigen >25% of saturation(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

12.05.2004(57) (58)Type
Species
Exposure period
Unit
LC50
Limit Test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

other: not specified
Daphnia magna (Crustacea)
48 hour(s)
mg/l
18.8
no
no dataother: according to the method described by Parkhurst et al. 19771979
noother TS: m-cresol, no purity reported

Method:Test condition:

Test substance
Reliability::

Parkhurst BR, Gehrs CW, Rubin IB (1977): Proceedings of ASTM
2nd Annual Symposium on Aquatic Toxicology, 122-130
Daphnia magna used in the test were adults.
100-ml test beakers were filled with 80 ml test solution and
4 daphnia. All the tests were run in triplicate.
Temperature during the test: 25 +/- 0.5°C
12h light/dark cycle
Test solution was prepared with filtered spring water (pH
7.8 alkalinity mg/l, hardness 140 mg/l)
Control beakers were used
48h-EC50 values were obtained by PROBITThe test substance was obtained from an effluent(2) valid with restrictions
Study well documented (method description in an otherreference) with some restriccions. Age of daphnia used in
the test is not clear. Daphnias were "adults" and adults canbe older than 24h (24h is suggested in the guideline);
temperature was 25°C (in guideline is suggested: 18-22°C);
12 daphnia were used for each test concentration (inguideline are suggested: 40)

12.05.2004

(59)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

staticDaphnia sp. (Crustacea)
48 hour(s)
mg/l
28
no

Method:Remark:Test condition
Reliability::

test organisms were reared from daphnids collected insurface water
TT = Toxicity threshold; test organisms were reared fromdaphnids collected in surface water
river water, pH 7.5(3) invalid

334

1959
no
other TS: m-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004
Experimental details missing. Study does not follow any
guideline, concentrations tested were not reported, no
information about the application method of the test
substance is given. Neither O2/pH monitoring nor analyticalmonitoring were applied

12.05.2004

(60)

Type
Species
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

ResultReliability::

other aquatic mollusc: Glossosiphonia complanata

other TS: m-cresol, no purity reported
perturbation level: 1.1 mg/l(4) not assignable
Secondary literature

12.05.2004

(61)

Type
Species
Exposure period
Unit
LC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Reliability:

other aquatic arthropod: Limnoria tripunctata
100 hour(s)
mg/l
100

other TS: m-cresol(4) not assignable
Reference not available

11.02.2003
4.3

(54)

TOXICITY TO AQUATIC PLANTS E.G. ALGAE

Species
Endpoint
Exposure period
Unit
TT
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Scenedesmus quadricauda (Algae)
biomass
8 day(s)mg/l
15Method:Remark:Test condition
Reliability::

incubation of 10 ml test solution (algae in defined mineralsalts medium)TT (toxic threshold concentration) refers to nominal test
substance concentration and was determined at 3 %effect compared to the control
27 degrees C; initial pH 7.0(3) invalid
It is unclear whether the algae are within the exponential
growth throughout the whole exposure period of 8 days.

noother: Cell multiplication inhibition test
1977
noother TS: m-cresol, no purity reported

12.05.2004(62)

UNEP PUBLICATIONS

335

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Species
Endpoint
Exposure period
Unit
EC0
EC50
EC100
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

Chlorella pyrenoidosa (Algae)
other: chlorophyll content
72 hour(s)
mg/l
> 50
127
250

Result:

Test condition:

Reliability:

1000 mg/l: complete destruction of chlorophyll
EC50 was not reported in the study, but it can be taken from the graph
TEST ORGANISMS- Strain: Emerson strain- Test temperature: 25 +- 1 degrees C- pH: 7.0
- Photoperiod: continuous illumination
TEST PARAMETER: chlorophyll(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

no
1968
no
other TS: m-cresol, no purity reported

12.05.2004(63)

Species
Endpoint
Exposure period
Unit
TGK
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Microcystis aeruginosa (Algae, blue, cyanobacteria)
other: cell multiplication
8 day(s)mg/l
13Remark:Reliability:

TGK = Toxicity treshold, determined at 1% effect compared tocontrol(3) invalid
It is unclear whether the algae are within the exponential
growth throughout the whole exposure period of 8 days.

noother: Modified DEV L9 (cell multiplication inhibition test)
1975
noother TS: m-cresol, no purity reported

12.05.2004
Species
Endpoint
Exposure period
Unit
NOEC
LOEC
EC50
EC100
Limit test
Analytical monitoring
MethodYear
GLP
Test substance336(64) (65)
:
:
:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton lucens
other: photosynthesis
21 day(s)
mg/l
.22
.65
.65
> 1.08no1983
noother TS: m-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

MethodTest condition
Reliability

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 uS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions notindicated. No information about application mode, number ofplants, controls, test concentrations, statistics,
analytics.

12.05.2004(66)

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton coloratus
other: photosynthesis
21 day(s)mg/l
1.08> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 uS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions notindicated. No information about application mode, number ofplants, controls, test concentrations, statistics,
analytics.

no
1983
no
other TS: m-cresol, no purity reported

12.05.2004(66)

Species
Endpoint
Exposure period
Unit
NOEC
LOEC
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:

other aquatic plant: Potamogeton crispus
other: photosynthesis
21 day(s)mg/l
1.08> 1.08

MethodTest condition
Reliability:::

simulation of running water under summer climate conditions
water hardness: 9° dH; conductivity: 300 uS; pH 7.8(3) invalid
Methodological deficiencies. Most test conditions notindicated. No information about application mode, number ofplants, controls, test concentrations, statistics,
analytics.

no
1983
no
other TS: m-cresol, no purity reported

12.05.2004
Species
Endpoint
Exposure period
Unit
Method
Year
GLP

(66)
:
:
:
:
:
:
:

Agmenellum quadruplicatum (Algae)

1974
no

UNEP PUBLICATIONS

337

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Test substance:other TS: m-cresol, no purity reported

Method:Result:Reliability:

algae cells embedded in agar, test substance absorbed ondiscs (12.7 mm) which are placed directly on the agar
surfaceincubation 5 to 8 days
no effect with 0.5 mg test substance on the platewith 1 mg inhibition between 1 to 10 mm from the disc edge,
with 10 mg complete killing within a zone of 36 mm(3) invalid
Unsuitable test system

12.05.2004(67)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

other algae: Chlorella autotrophica

Method:Result:Reliability:

algae cells embedded in agar, test substance absorbed ondiscs (12.7 mm) which are placed directly on the agar
surfaceincubation 5 to 8 days
with 1 mg inhibition between 1 to 4 mm from the disc edge,
with 2 mg 1nhibition between 3 to 35 mm from the disc edge
(3) invalid
Unsuitable test system

1974
noother TS: m-cresol, no purity reported

12.05.2004(67)

Species
Endpoint
Exposure period
Unit
TT
Limit test
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

Scenedesmus quadricauda (Algae)
biomass
96 hour(s)mg/l40RemarkReliability::

TT = toxicity treshold(3) invalid
Methodological deficiencies

noother: Cell multiplication inhibition test
1959
noother TS: m-cresol, no purity reported

12.05.2004(60)

Species
Endpoint
Exposure period
Unit
MTL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

Ankistrodesmus falcatus (Algae)
biomass
10 day(s)mg/l
100

Method:described in: Denson & Bold, The University of Texas
Publication No. 6022, 72 (1960)

338

1976
other TS: m-cresol, no purity reported

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

RemarkResult::Reliability:

MTL = median tolerance limit
sublethal concentration 100 mg/l
lethal concentration 500 mg/l(4) not assignable
Insufficient documentation

12.05.2004
4.4

(68)

TOXICITY TO MICROORGANISMS E.G. BACTERIA

TypeSpecies
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
activated sludge, domestic
3 hour(s)
mg/l
461.4
no
OECD Guide-line 209 "Activated Sludge, Respiration Inhibition Test"
1985
noother TS: m-cresol, reagent grade

Remark:Test condition
Reliability

:
:

Flag
12.05.2004:

synthetic sewage stock solution slightly different from OECD
guideline; reference substance 1,5-dichlorophenol
21 degrees C; continuous aeration with 0.5-10 l/min(1) valid without restriction
Guideline study
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
EC75
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
activated sludge of a predominantly domestic sewage

Method:RemarkTest condition
Reliability

:
:
:

Flag
12.05.2004:

Quantitative determination of the nitrification rate (1ststep, NH4 to NO2),
colorimetric measurement of the NO2/NO3 concentration;
static test system
Pre-cleaned activated sludge in particle-free communal waste
water (BOD5: 250 mg/l; NH4-N/l: 50-80 mg)
effect: inhibition of ammonia oxidation
Exposure period: 2-4 h; 25 degree C; pH 7.6-7.8(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation
Critical study for SIDS endpoint

Type
Species
Exposure period
Unit
Analytical monitoring
Method

:
:
:
:
:
:

(69)

mg/l
11.4
no
other: inhibition of nitrification process
1966
noother TS: m-cresol, no purity reported(70)
aquatic
other bacteria
no
other

UNEP PUBLICATIONS

339

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Year
GLP
Test substance

:
:
:

1985
no
other TS: m-cresol, purity 99.5 %Method:Result:

Test condition
Test substance
Reliability:::

6 different pure bacteria cultures: 3 isolated from alaboratory activated sludge, 2 from activated sludge from amunicipal plant receiving some industry wastewater, and 1
from a lake sediment
Effect: 50 % resazurin reduction (determination of
dehydrogenase activity)from laboratory sludges: EC50 = >500, 225, and 410 mg/l
from activated sludges: EC50 = 360 and >500 mg/l
from lake sediment: EC50 = >500 mg/l
21 degrees C; incubation 30-60 min
purity 99.5%(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(71)

Type
Species
Exposure period
Unit
IC 50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Aerobic heterotrophic
49 hour(s)
mg/l
440
no

MethodRemark::Test condition
Reliability::

culture obtained from mixed liquor of a treatment plant
Effect: inhibition of respiration; prolonged incubationcompared with ISO 8192
25 and 35 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

1991
noother TS: m-cresol, no purity reported

12.05.2004

(72)

Type
Species
Exposure period
Unit
IC 50
Analytical monitoring
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

RemarkTest condition
Reliability:::

aquatic
other bacteria: Methanogenic bacteria
96 hour(s)
mg/l
890
no
other: Owen, W.F.: Bioassay for Monitoring Biochemical Methane Potential
and Anaerobic Toxicity. Water Res. 13, 485 (1979)1991
noother TS: m-cresol, no purity reported
Effect: inhibition of gas production
35 degrees C(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

12.05.2004

340

(72)

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Type
Species
Exposure period
Unit
IC 50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Nitrosomonas sp. (Bacteria)
24 hour(s)
mg/l
.78
no
other: Inhibition of nitrification, comparable to ISO/DIS 9509
1991
noother TS: m-cresol, no purity reported

MethodRemarkTest condition
Reliability

:
:
:
:

culture obtained from mixed liquor of a treatment plant
Effect: inhibition of N-oxidation
25 degrees C(3) invalid
In principal the test is comparable to standard methods,
but the authors state that the compounds with log IC50<1,5umol/l had questionable accurate results, so that thiseffect value has to be considered invalid.

12.05.2004

(72)

Type
Species
Exposure period
Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
anaerobic microorganisms

Method:Result:Reliability:

phenol-enriched methanogenic culture
nominal concentrations 50, 100, 150, 250, 300, 400, 500, and
700 mg/l m-cresol + 200 mg/l phenol
incubation at 35 degrees C
m-cresol concentrations above 150 mg/l inhibited theanaerobic phenol degradation(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

yes
1989
no
other TS: m-cresol, no purity reported

12.05.2004

(35)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Pseudomonas putida (Bacteria)
16 hour(s)
mg/l
53
no
other: Cell multiplication inhibition test
1977
noother TS: m-cresol, no purity reported

Remark:Reliability:

TT = Toxicity threshold; determined at 3 % effect compared
to control(2) valid with restrictions
Test procedure comparable to standard method and inaccordance with generally accepted scientific standards;
sufficient documentation

UNEP PUBLICATIONS

341

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

12.05.2004(65) (62)Type
Species
Exposure period
Unit
EC10
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Mixed marine bacteria culture
16 hour(s)
mg/l
33.4
324 - 326
noother: Static bioassay (determination of bacterial growth)
1989noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

mixed culture of 13 unidentified bacterial strains isolated
from sea water
Incubation at 25-30 degrees Celsius, artificial saltwater(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004(73) (74)Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Chilomonas paramaecium (Protozoa)
48 hour(s)
mg/l
114
no
other: cell multiplication inhibition test1980
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

TT = Toxicity threshold; determined at 5 % effect compared
to control
20 degrees C; initial pH 6.9(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(75)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Entosiphon sulcatum (Protozoa)
72 hour(s)
mg/l
31
no
other: cell multiplication inhibition test
1978
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

TT = Toxicity threshold; determined at 5 % effect compared
to control
25 degrees C; initial pH 6.9(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail342

UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

12.05.2004

(76)

Type
Species
Exposure period
Unit
LC100
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Tetrahymena pyriformis (Protozoa)
24 hour(s)
mg/l
375
no

Test condition
Reliability::

28 degrees C(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail1978
noother TS: m-cresol, no purity reported

12.05.2004

(77)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Uronema parduzci (Protozoa)
20 hour(s)
mg/l
62
no
other: cell multiplication inhibition test1980
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

TT = Toxicity threshold; determined at 5 % effect compared
to control
25 degrees C; initial pH 6.9(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(78)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Photobacterium phosphoreum (Bacteria)
5 minute(s)
mg/l
11
no
other: Microtox assay
1983
no dataother TS: m-cresol, no purity reported

Remark:Reliability:

effect: reduction of bioluminescence
Secondary literature. Not enough information supplied forassessment. Although the author suggests that Microtox maylack reproductibility due to variations in bacterial cellsuspensions, no information is supplied on the maintenanceof the lyophilized bacteria, their age, duration ofreconstitution and other important parameters.
(3) invalid
Unsuitable test system. Organisms are of marine origin.
Method is not appropriate for the hazard assessment of

UNEP PUBLICATIONS

343

OECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004
chemicals.

12.05.2004

(79)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Photobacterium phosphoreum (Bacteria)
15 minute(s)
mg/l
8
no
other: Microtox assay
1987
noother TS: m-cresol, analytical grade (either from Merck or EGA Chemie)

Remark:Reliability:

Not enough information supplied for assessment of the test
used (Test done according to Beckman manual). Although it issuggested that Microtox may lack reproducibility due tovariations in bacterial cell suspensions [Bitton G (1983)
Bacterial and Biochemical Tests for Assessing Chemical
Toxicity in the Aquatic Environment: A Review. Crit Rev
Environ Control 13: 51 -67], no information is supplied on
the maintenance of the lyophilized bacteria, their age,duration of reconstitution and other important parameters.
(3) invalid
Unsuitable test system. Organisms are of marine origin.
Method is not appropriate for the hazard assessment ofchemicals.

12.05.2004

(80)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Photobacterium (Vibrio) fischeri (marine)
5 minute(s)
mg/l
8.2
no
other: Microtox assay
1981
noother TS: m-cresol, no purity reported

Remark:Test condition
Reliability::

Although it is suggested that Microtox may lack
reproducibility due to variations in bacterial cellsuspensions [Bitton G (1983) Bacterial and Biochemical Tests
for Assessing Chemical Toxicity in the Aquatic Environment:
A Review. Crit Rev Environ Control 13: 51 -67], no
information is supplied on the maintenance of thelyophilized bacteria, their age, duration of reconstitution
and other important parameters. In contrast to Bulich[Bulich AA (1977), Aquatic Toxicology: Second conference
ASTM STP 667, American Society for Testing of Materials,
Philadelphia, pp 98 - 106], pH not buffered.
15 degrees C(3) invalid
Unsuitable test system. Organisms are of marine origin.
Method is not appropriate for the hazard assessment ofchemicals.

12.05.2004
Type
Species
Exposure period

344

(81)
:
:
:

aquatic
Escherichia coli (Bacteria)
19 day(s)UNEP PUBLICATIONSOECD SIDS
4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:

MethodResult::

Test condition
Reliability

:
:

no
1983
no
other TS: m-cresol, no purity reported
Incubation in microcosms containing sterile sea water
Number of viable cells remained constant
Number of culturable cells decreased, no plasmids weredetected. Changes in membrane protein composition observed.
After transfer into rich medium without test substance,
growth resumed and plasmids were again detectable.
Test concentration 1 µg/l, 18 degrees C(3) invalid
Tested organism not relevant for environment

12.05.2004(82) (83)Type
Species
Exposure period
Unit
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
Pseudomonas putida (Bacteria)
48 hour(s)MethodResult
Test condition
Reliability

:
:
:
:

in the culture medium absorbance at 660 nm was measured
absorbance 0.46 with 0.5 g/l and 0.22 with 1 g/l
30 degrees C(3) invalid
Experimental details missing

no
1989
no
other TS: m-cresol, no purity reported

12.05.2004

(84)

Type
Species
Exposure period
Unit
EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Photobacterium phosphoreum (Bacteria)
30 minute(s)
mg/l
11.8
no
other: Microtox
1981

Remark:Test condition
Reliability::

Inhibition of bioluminescence
Secondary literature; not enough information for assessmentof cited result
20 degrees C(3) invalid
Unsuitable test system. Organisms are of marine origin.
Method is not appropriate for the hazard assessment ofchemicals

other TS: m-cresol, no purity reported

12.05.2004

(85)

Type
Species::

Exposure period
Unit

:
:

aquatic
other bacteria: gentechnologically constructed luminescent bacteria
originating from wastewater treatment plant
30 minute(s)mg/lUNEP PUBLICATIONS

345

OECD SIDS
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ID: 15831-10-4
DATE: 24.05.2004

EC50
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:

68 measured/nominalnoother: Microtox assay
1986
no dataother TS: m-cresol, no purity reported

Remark:Test condition:

Reliability:

Inhibition of bioluminescence
Modified microorganisms used which represent the metabolic
potentials present in a wastewater treatment plant and someproperties of a marine organism, but which are not identicalto any known species in natural environments- Wastewater bacteria (Eschericia coli) which were obtained
from a wastewater treatment plant- Bacteria obtained the luciferase operon of Vibrio fischeri
by transfer from luminescent E. coli
- Incubation at 20 °C- Result calculated from the difference of the luminescence
between controls and test substance taking into account thelight emissions at 0 and 20 °C(3) invalid
Unsuitable test system. Organisms are of marine origin.
Method is not appropriate for the hazard assessment ofchemicals.

12.05.2004

(85)

Type
Species
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

aquatic
Escherichia coli (Bacteria)
2 hour(s)
mg/l
1000

Result:

Test condition
Reliability::

endpoint related to growth inhibition
no effect on cell size
37 degrees C(3) invalid
Methodological deficiencies

1954
other TS: m-cresol, no purity reported

12.05.2004

(86)

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Escherichia coli (Bacteria)

Method:Remark:Reliability:

test organisms isolated from river water
endpoint: inhibition of glucose metabolism
TT = toxicity treshold; determined at 5 % effect compared tocontrol(3) invalid
Methodological deficiencies

mg/l
600
no
1959
no
other TS: m-cresol, no purity reported

12.05.2004

346(60) (87)

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4. ECOTOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Type
Species
Exposure period
Unit
TT
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
Pseudomonas fluorescens (Bacteria)

Remark:Reliability:

TT = toxicity treshold; determined at 5 % effect compared tocontrol
endpoint: inhibition of glucose metabolism(3) invalid
Methodological deficiencies

mg/l
40
no
1960
no
other TS: m-cresol, no purity reported

12.05.2004

(60)

Type
Species
Exposure period
Unit
EC0
Analytical monitoring
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

aquatic
other bacteria: Pseudomonas Stamm Berlin 33/2

RemarkReliability::

Effect endpoint: cell multiplication inhibition(4) not assignable
Insufficient documentation

mg/l
180
no
other
1982
no
other TS: m-cresol, no purity reported

12.05.2004

(47)

Type
Species
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

aquatic
Paramaecium caudatum (Protozoa)

ResultReliability::

pertubation level 0.9 mg/l(4) not assignablesecondary literatureother TS: m-cresol, no purity reported

12.05.2004

(61)

Type
Species
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

aquatic
other protozoa: Vorticella campanula

ResultReliability::

pertubation level 0.5 mg/l(4) not assignablesecondary literatureother TS: m-cresol, no purity reported

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4.5.1

CHRONIC TOXICITY TO FISH

4.5.2

CHRONIC TOXICITY TO AQUATIC INVERTEBRATES

4.6.1

TOXICITY TO SEDIMENT DWELLING ORGANISMS

4.6.2

TOXICITY TO TERRESTRIAL PLANTS

Species
Endpoint
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other terrestrial plant: Lactuca sativa Ravel R2
growth14 day(s)mg/kg soil dw
96
OECD Guide-line 208 "Terrestrial Plants, Growth Test"
1993
no dataother TS: m-cresol, purity >= 95 %MethodResult::Reliability:

Flag
12.05.2004:

analytical monitoring at start and end of test
EC50 based on nominal concentration; for most of theexamined
phenols (including m-cresol) applied concentrations dropped
to < 20% of the nominal values(2) valid with restrictions
Guideline study; applied test concentrations not stable
during the test period
Critical study for SIDS endpoint

Species
Endpoint
Exposure period
Unit
EC50
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other terrestrial plant: Lactuca sativa Ravel R2
growth16 day(s)mg/l50

Method:Result:Reliability:

semistatic test in nutrient solution, renewed 3 times/week
nutrient solution as described in Steiner, A.A.: Soilless
culture. Proceedings, Sixth Colloqium of the International
Potash Institute, Florence, Italy, 324-341 (1968);
analytical monitoring of TS at start and end of exposure andbefore renewal of test solution
EC50 based on nominal concentration; TS concentration before
renewal of test solution > 50% of initial concentration(3) invalid
unsuitable test system

(88)

1993
no dataother TS: m-cresol, purity >= 95 %11.02.2003
Species
Endpoint

348

(88)
:
:

Raphanus sativus (Dicotyledon)other: germination and growth rate

UNEP PUBLICATIONSOECD SIDS
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m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:

4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilled water
24 degrees C, 10h light, 14 h dark
3 replicates of 20 seeds
Concentr. Germination rate% Growth rate %g/l
1 day 4 days Radicle Hypocotyl

Reliability

:

1989
no
other TS: m-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10
0
0
1
0
5.3
2.0
0.1
82.6
95.0
80.8
(3) invalid
Methodological deficiencies

104.7

12.05.2004(89)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Brassica rapa (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilled water
24 degrees C, 10h light, 14 h dark
3 replicates of 20 seeds
Concentr. Germination rate% Growth rate %g/l
1 day 4 days Radicle Hypocotyl

Reliability

:

1989
no
other TS: m-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10
0
0
1
0
0
0.1
85.8 91.5
54.9(3) invalid
Methodological deficiencies

72.8

12.05.2004(89)

Species
Endpoint
Exposure period
Unit
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:

Brassica campestris var. chinensis (Dicotyledon)other: germination and growth rate
4 day(s)g/lMethod:Result:seeds exposed to test compounds dissolved in distilled water
24 degrees C, 10h light, 14 h dark
3 replicates of 20 seeds
Concentr. Germination rate% Growth rate %g/l
1 day 4 days Radicle Hypocotyl

1989
noother TS: m-cresol, special grade purity (obtained from Wako Pure
Chemicals Industries, Ltd.)

10

0

0

-

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Reliability

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

:

1
0
0
0.1
100
100
86.5
(3) invalid
Methodological deficiencies

77.1

12.05.2004

(89)

4.6.3

TOXICITY TO SOIL DWELLING ORGANISMS

4.6.4

TOX. TO OTHER NON MAMM. TERR. SPECIESSpecies
Endpoint
Exposure period
Unit
LD50 oral
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:

other avian: Agelaius phoeniceus (red-winged blackbird)
mortality

Test condition:

Reliability:

birds pre-conditioned to captivity for 2 to 6 weeks
dosed by gavage with solution in propylene glycol or bypellets resp. gelatin capsules(2) valid with restrictions
Unsuitable test system

mg/kg bw
113
1983
no dataother TS: m-cresol

11.02.2003

(90)

4.7

BIOLOGICAL EFFECTS MONITORING

4.8

BIOTRANSFORMATION AND KINETICS

Remark:Test substance
Reliability::

In aquarium water of 12 species of freshwater fish 48 h
after exposure to 3-15 mg/l m-cresol, cresyl sulphate(55-64% of 14C recovered) or m-hydroxybenzoic acid (0-39 %)were foundIn bile of 11 species, cresyl glucuronide (63-74 %), cresyl
sulphate (8-20 %) and m-hydrobenzoic acid (5-12 %) were
foundUnchanged m-cresol detected in both aquarium water and bile
m-[U-14C]cresol(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail17.10.2001
4.9

(91)

ADDITIONAL REMARKS

Memo

:

Sea urchin test

Remark:Strongylocentrotus droebachiensis (sea urchin):static test, 5 degrees C
Determined effect endpoints: death, pathology, inhibition of

350

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ID: 15831-10-4
DATE: 24.05.2004

Test substance:

Reliability:

cleavage and differentiation, pigment defects
EC50 (96 h): ca. 30 mg/lother TS: m-cresol, purity > 98 % as determined by GC (obtained from
Merck)(2) valid with restrictions
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficientdetail12.05.2004

(46)

Memo

:

Tree neoplasms

Remark:Test substance
Reliability::

m-cresol (1.5 % v/v) showed a toxicity rating from 3-4 (0 =no injury, 5 = complete kill within 14 d) in tomato crowngall tumors incited by Agrobacterium tumefaciens.
other TS: m-cresol, no purity reported(3) invalid
Unsuitable test system

12.05.2004

(92)

Memo

:

Hela cell screening

Remark:Test substance
Reliability::

In a rapid-cell culture assay with HeLa cells, m-cresol (4x10-5 to 4x10-3 M,
4 h incubation) showed a concentration-dependent inhibition of 3H labeledthymidine incorporation into DNA incubation 4 hother TS: m-cresol, no purity reported(3) invalid
Unsuitable test system(93) (94)12.05.2004
Memo:

MolluscRemark:Test substance
Reliability::

Teredo diegensis (Mollusca):
LC50 (72 h): 100 mg/lother TS: m-cresol, no purity reported(4) not assignable
Reference not available

12.05.2004(54)

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351

OECD SIDS
5. TOXICITY

5.0

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

TOXICOKINETICS, METABOLISM AND DISTRIBUTIONIn Vitro/in vivo
Type
SpeciesNumber of animals
Males
Females
Doses
Males
Females
Vehicle:::Result:Reliability:

In vivo
Toxicokinetics
other

:
:
:
:
:

09.01.2003

At physiological pH, the conjugated metabolite of phenolic
compounds are ionized to a greater extent than the parent
compound, which reduces renal reabsorption and increases
elimination with the urine.
In addition to urinary excretion, cresols are excreted in
the bile, butr the most part undergoes enterohepatic
circulation.
there are known species differences in the specificconjugation reactions of cresol isomers. The relative
amounts of gluucuronide and sulfate conjugates therefore
differ between species and also vary with dose.
(2) valid with restrictions
basic information(95) (96) (97) (98)5.1.1

ACUTE ORAL TOXICITY

5.1.2

ACUTE INHALATION TOXICITY

17.06.2002
5.1.3

ACUTE DERMAL TOXICITY

17.06.2002
5.1.4

ACUTE TOXICITY, OTHER ROUTES

17.06.2002
5.2.1

SKIN IRRITATION

Species
Concentration
Exposure
Exposure time

352

:
:
:
:

rabbitundiluted
Semiocclusive
4 hour(s)UNEP PUBLICATIONSOECD SIDS
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m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Number of animals
VehiclePDII
ResultClassification
Method

:
:
:
:
:
:

Year
GLP
Test substance:::

Method:Result:Reliability:

Flag
16.12.2002

:

5.2.2

EYE IRRITATION

5.3

SENSITIZATION

3
other: none
corrosiveother: in accordance with classification of corrosive hazards, Fed. Reg. Vol.
37, No.57, §173.240 - D.O.T., see freetext ME
1972
noother TS: no data on purity and composition of mixture
0.5 ml of undiluted sample was applied to the clipped,
intact skin of 3 New Zealand white male and female rabbits
under 1 inch square patch, 2 single layers thick. The
patches were held in place with adhesive tape in such amanner that evaporation was retarded, but not prevented, forthe 4 hour exposure period.
The data were scored according to the method of Draize,
Woodward and Calvery (J. of Pharm. Exp. therapeutics Vol.
82, December, 1944)
4-Hours: necrosis, severe edema
24 hours: eschar formation (corrosive)
Scab sloughed off in 14 - 17 days showing injury in depth(2) valid with restrictions
only a summary description: individual animal data notgiven, no purity of the TS given
Critical study for SIDS endpoint
(99)

Type
SpeciesNumber of animals
VehicleResultClassification
Method

:
:
:
:
:
:
:

Year
GLP
Test substance:::

Reliability:

Flag
05.02.2004

:

other
guinea pig
other: acetone
not sensitizing
other: a 7,5 % solution of a mixture of m- and p-cresol in acetone wasrepeatedly supplied to the skin of guinea pig
1998
no dataother TS: mixture of m- and p-cresol, not specified further(2) valid with restrictions
limited documentation
Critical study for SIDS endpoint(100)

04.12.2002
5.4

REPEATED DOSE TOXICITY

Type
Species::

Sub-chronic
rat

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ID: 15831-10-4
DATE: 24.05.2004

Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:

male/female
other: F334/N
oral feed
13 w
continuously in feed
no0, 1880, 3750, 7500, 15000, 30000 ppm (see RM)
yes, concurrent no treatment
3750 ppm
other: see freetext ME1991
yesother TS: m-/p-cresol (60%:40% mixture)

Method:SIZE OF STUDY GROUP:
20 male and 20 female rats (10 of each group designated forclinical pathology studies)
TIME HELD BEFORE STUDY: 12-13 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into
groups per sex
DIET: NIH-07 rat ration
ANIMAL ROOM ENVIRONMENT:
temperature: 72° +/-3° F, humidity: 50 % +/-15 %,Fluorescent light: 12 hrs/day, room air changes: 10-12
changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly,
and at termination, feed consumption by cage recorded twice
weeklyNECROPSY AND HISTOLOGIC EXAMINATION:
necropsy performed on all animals. A complete
histopathologic examination was conducted on all control
animals, all animals in the highest dose group with at least
60 % survivors at study termination, and all aninmals inhigher dose groups inclusive of early deaths. The following
organs and/or tissues were included in complete
histopathological examinations, as well as any tissue
masses, gross lesions, and associated regional lymph nodes:
adrenals, aorta, bone (sternebrae, femur, or vertebrae,including marrow), brain, bronchi, clitoral gland,
epididymis, oesophagus, heart, kidney, large intestines(caecum, colon,rectum), liver, lungs, lymph nodes(mesenteric), mammary glands, nasal cavity and turbinates,
oral cavity, ovaries, pancreas, parathyroids, pharynx,
pituitary, preputial gland, prostate, salivary glands,
scrotal sac, seminal vesicles, skin, small intestine(duodenum, ileum, jejunum), spleen, stomach, testes, thymus,
thyroid, tongue, trachea, tunica vaginalis, urinary bladder,uterus and Zymbal's glands. For lower level dose groups, allgross lesions and the following target organs were examinedhistopathologically: bone marrow, nasal mucosa, thyroid
gland, uterus. Organ weights recorded for brain, liver,right kidney, thymus, heart, and lungs of all animals, andthe right testis of all males.
HAEMATOLOGIC, CLINICAL CHEMISTRY, and URINALYSIS
determinations included.
haematocrit, haemoglobin, red blood cell count, mean cellvolume (only females), meam cell haemoglobin, mean cellhaemoglobin concentration (only females), platelets,
reticulocytes, white blood cell count, lymphocytes,

354

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ID: 15831-10-4
DATE: 24.05.2004

Remark:Result:monocytes, eosinophila, urea nitrogen, alanine
aminotransferase, alkaline phosphatase, 5'-nucleotidase,
sorbitoldehydrogenase, bile acids, urine aspartate
aminotransferase, urine n-acetyl-ß-glucose amidase, urine
volume, specific gravity
reproductive toxicity evaluation as described in chapter
5.8.3.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test,
arcine transformation,
multivariate analysis of variancemean compound consumption (mg/kg bw/day):males
females0 ppm
001880 ppm
123
131
3750 ppm
241
254
7500 ppm
486
509
15000 ppm
991
1024
30000 ppm
2014
2050
All rats lived to the end of the study;
clinical signs of toxicity: 30000 ppm: males, females, roughhair coat, urine-stained fur; females, thin appearance;
15000-3750 ppm: females, urine stained fur
15000, 30000 ppm: males, females, final body weight reduced;
females, reduced weight gain; 30000 ppm: males, weight gain
reduced; males, females, reduced feed consumption during thefirst week
At study termination weights (w) were sign. increased(mainly p </= 0.05):
Brain (males, rel. w. at 30000 ppm ; females, rel. w. from
15000 ppm), heart (males, abs. w. from 15000 ppm; females,abs. w. at 30000 ppm), lungs (males, females, abs. w. from
15000 ppm; males, rel. w. at 30000 ppm), thymus ( males andfemales abs. w. at 30000 ppm), right kidney (male,rel. w.
from 7500 ppm, abs w from 15000 ppm; females: rel. w. at
30000 ppm), liver (males, abs. w. from 3750 ppm, rel. w.
from 7500 ppm; females, rel. and abs. w from 7500 ppm) andin males relative weights of right testes from 15000 ppm.
Microscopically, the following changes were reported (contr.
low to high dose, average severity score based on a scale of
1 to 4 given[1 = minimal, 2 = mild, 3 = moderate, 4 =marked]):Nose (respiratory epithelium hyperplasia, male: 0/10,
3/10[1.0], 8/10[1.1], 10/10[1.4], 8/10[2.2],10/10[3.8];
female: 3/10[1.0],1/10[1.0], 5/10[1.2], 9/10[1.7],
8/10[2.0], 10/10[2.8] and glandular hyperplasia, male: 0/10,
3/10[1.0], 8/10[1.5], 10/10[1.6], 9/10[2.6], 9/10[3.8];
female: 0/10, 2/10[1.0], 6/10[1.3], 10/10[2.1], 8/10[2.5],
6/10[2.8], no evidence of other inflammatory or degenerativechanges),thyroid gland (increased colloid in follicles: males: 0/10,
0/10, 0/10, 0/10, 7/10[1.1], 9/10[1.6]; females: 0/10, 0/10,
0/10, 0/10, 6/10[1.0]),
the biological significance is uncertain (the effect was notnoted in studies with the individual isomers, nor was it
associated with overt follicular cell hypertrophy and/or
hyperplasia)
bone marrow (hypocellularity: males: 0/10, 0/10, 0/10, 0/10,
1/10[1.0], 8/10[1.0]; females: 0/10, 0/10, 0/10, 0/10, 0/10,

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DATE: 24.05.2004
6/10[1.0]) anduterus atrophy in females: 0/10, 0/10, 0/10, 0/10,
3/10[1.0], 7/10[1.7].
Evaluation of other reproductive organs (see also chapter
5.8.3) revealed no significant findings in males but
lengthened oestrus cycle in females significant from 7500
ppm
Haematology, clinical chemistry, urinalysis data (only sign.
changes, incidences not given):haematocrit (male, female, increase, 30000 ppm, d5; female,decrease, d43 from 15000 ppm), haemoglobin (increase, male,
female, d5, 30000 ppm), red blood cell count (increase,male, female, d5, d21, 30000 ppm), mean cell volume(decrease, female, 30000 ppm at d5, from 15000 ppm d21 tod90), mean cell haemoglobin (decrease, female, 30000 ppm,
d21, d90), mean cell haemoglobin concentration (increase,female, from 15000 ppm d5, d43), platelet count (increase,male, 15000 ppm, d21; 30000 ppm, d21, d43; female, d21 from7500 ppm, d43 at 15000 ppm), reticulocytes (decrease,female, from 15000 ppm d5), white blood cell count(increase, male, d21, 15000 ppm), lymphocytes (male,increase, d21, 15000 ppm), monocytes (male, increased from1880 ppm at d5; female, decrease d90 at 30000 ppm),
urea nitrogen (male, increase, from 15000 ppm at d5,
decrease from 1880 ppm at d43 and from 15000 ppm at d90;
female, increase at d 5 from 3750 ppm, decrease at d43 from3750 ppm),
alanine aminotransferase (increase, d5: male, 30000 ppm,
female from 15000 ppm), alkaline phosphatase (male,decrease, d21 from 15000 ppm, d43, 7500 ppm, 30000 ppm),
5'-nucleotidase (decrease, male, d5 30000 ppm, d21 from 3750
ppm, d43 from 7500 ppm, d90 30000 ppm: female, d5 from 15000
ppm, d21, d43 from 7500 ppm, d90 from 3750 ppm), sorbitol
dehydrogenase (male, increase d5 from 7500 ppm), bile acids(increase, male, d5 from 15000 ppm and at 30000 ppm, d21,
d43, and d90 at 3750 ppm and 30000 ppm; female, d21 from1880 ppm, d43 from 15000 ppm, d90 30000 ppm),
urine aspartate aminotransferase (male, increase, d43, d90,
from 7500 ppm; female, decrease, d41, from 3750 ppm), urine
N-acetyl-ß-glucose aminidase (increase, male, d41, from 7500
ppm, d90 from 15000 ppm; female, d90 30000 ppm), urine
volume (decrease, male, d41 30000 ppm, d90 from 7500 ppm),
specific gravity (increase, male, d41,d90, from 7500 ppm)

Reliability
Flag
16.12.2002

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses

:
:
:
:
:
:
:
:
:

356

local toxicity: NOAEL(male, female): < 1880 ppm
systemic toxicty: NOAEL(male, female): 3750 ppm(1) valid without restriction
Critical study for SIDS endpoint(101)
Sub-chronicmouse
male/female
B6C3F1oral feed
13 w
continuously in feed
no0, 625, 1250, 2500, 5000, 10000 ppm (see RM)

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m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Control group
NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:

yes, concurrent no treatment
2500 ppm
other: see freetext ME1991
yesother TS: m-/p-cresol (60%:40% mixture)

Method:SIZE OF STUDY GROUP:
10 male and 10 female mice per group
TIME HELD BEFORE STUDY: 12-13 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into
groups per sex
DIET: NIH-07 mouse ration
ANIMAL ROOM ENVIRONMENT:
temperature: 72° +/-3° F, humidity: 50 % +/-15 %,Fluorescent light: 12 hrs/day, room air changes : 10-12
changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly,
and at termination, feed consumption by cage recorded twice
weeklyNECROPSY AND HISTOLOGIC EXAMINATION:
necropsy performed on all animals. A complete
histopathologic examination was conducted on all control
animals, all animals in the highest dose group with at least
60 % survivors at study termination, and all aninmals inhigher dose groups inclusive of early deaths. The following
organs an/or tissues were included in complete
histopathological examinations, as well as any tissue
masses, gross lesions, and associated regional lymph nodes:
adrenals, aorta, bone (sternebrae, femur, or vertebrae,including marrow), brain, bronchi, clitoral gland,
epididymis, oesophagus, gallbladder, heart, kidney, large
intestines (caecum, colon,rectum), liver, lungs, lymph nodes(mesenteric), mammary glands, nasal cavity and turbinates,
oral cavity, ovaries, pancreas, parathyroids, pharynx,
pituitary, preputial gland, prostate, salivary glands,
scrotal sac, seminal vesicles, skin, small intestine(duodenum, ileum, jejunum), spleen, stomach, testes, thymus,
thyroid, tongue, trachea, tunica vaginalis, urinary bladder,uterus and Zymbal's glands. For lower level dose groups, allgross lesions and the following target organs were examinedhistopathologically: nasal mucosa. Organ weights recorded
for brain, liver, right kidney, thymus, heart, and lungs of
all animals, and the right testis of all males.
Haematologic, clinical chemistry, and urinalysis
determinations performed at necropsy. Sperm morphology andvaginal cytology< examinations were performed.
HAEMATOLOGY and CLINICAL CHEMISTRY DATA:
haematocrit, haemoglobin, red blood cell count, mean cellvolume (only male), mean cell haemoglobin, mean cellhaemoglobin concentration, platelets, reticulocytes, whiteblood cell count, urea nitrogen, creatinine, alanine
aminotransferase,alkaline phosphatase, 5'-nucleotidase,
sorbitol dehydrogenase (only male)
STATISTICAL METHODS:
nonparametric multiple comparisontest of Dunn and Shirley,
Jonckheere's test,
arcsine transformation,
multivariate analysis of variance

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ID: 15831-10-4
DATE: 24.05.2004

Remark:Result:mean compound consumption (mg/kg bw/day):males
females0 ppm
00625 ppm
96
1161250 ppm
194239
2500 ppm
402
472
5000 ppm
776
923
10000 ppm
1513
1693
All mice lived to the end of the study;
as clinical signs of toxicity rough fur in females of the10000 ppm-group.
10000 ppm: male, female reduced final body weight, slightly
decreased feed consumption, males: reduced body weight gain
At study termination significantly increased abs. and rel.
liver weight were noted from males at 5000 ppm (abs:p</=0.05; rel: p</=0.01) and 10000 ppm (p</=0.01) andrelative liver weights in females at 10000 ppm (p</=0.01).
Microscopical examination:
liver: no changes were observed (both sexes);
nose (contr. low to high dose, average severity score basedon a scale of 1 to 4 given[1 = minimal, 2 = mild, 3 =moderate, 4 = marked]):respiratory epithelium hyperplasia: male, 1/10[1.0], 0/10,
0/10, 0/10, 4/10[1.0], 8/10[1.0]; female, 2/10[1.5], 0/10,
0/10, 3/10[1.0], 2/10[1.0], 5/10[1.0]respiratory glandular hyperplasia: male, 1/10[1.0], 0/10,
0/10, 0/10, 0/10, 2/10[1.0]; female, 1/10[1.0], 0/10,0/10,
0/10, 07/10, 2/10[1.5]
Evaluation of reproductive organs revealed no biologicallysign. findings in males and females (see also chapter 5.8.3
for further information)
Hematology, clinical chemistry and urinalysis data (sign.
changes):
In males at 30000 ppm, d90.haemoglobin as significantly
reduced and Sorbitol dehydrogenase was significantly
increased. In Females hemoglobin was reduced on d90 at 30000
ppm and 5'-Nucleotidase was significantly increased on d 90
from 5000 ppm.

Reliability
Flag04.05.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
Method

:
:
:
:
:
:
:
:
:
:
:
:

358

local toxicity: NOAEL(male, female): 2500 ppm
systemic toxicity:
NOAEL(male): 2500 ppm; NOAEL(female): 5000 ppm(1) valid without restriction
Critical study for SIDS endpoint(101)
Sub-acuteratmale/female
other: F344/N
oral feed
28 dcontinuously in feed
no0, 300, 1000, 3000, 10000, 30000 ppm (see RM)
yes, concurrent no treatment
1000 ppm
other: see freetext ME

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5. TOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Year
GLP
Test substance

:
:
:

1991
yes
other TS: m-/p-cresol (60%:40% mixture)

Method:Remark:Result:

SIZE OF STUDY GROUP:
5 male and 5 female rats per group
TIME HELD BEFORE STUDY: 13-15 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into
groups per sex
DIET: NIH-07 rat ration
ANIMAL ROOM ENVIRONMENT:
temperature: 72° +/-3° F, humidity: 50 % +/-15 %,Fluorescent light: 12 hrs/day, room air changes : 10-12
changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly,
and at termination, feed consumption by cage recorded twice
weeklyNECROPSY AND HISTOLOGIC EXAMINATION:
necropsy and tissue collection performed for all animals. A
complete histopathologic examination was conducted on allcontrol animals, all animals in the highest dose group withat least 60 % survivors at study termination, and allaninmals in higher dose groups inclusive of early deaths.
The following organs and/or tissues were included incomplete histopathological examinations, as well as any
tissue masses, gross lesions, and associated regional lymph
nodes: adrenals, aorta, bone (sternebrae, femur, orvertebrae, including marrow), brain, bronchi, clitoral
gland, epididymis, oesophagus, heart, kidney, large
intestines (caecum, colon, rectum), liver, lungs, lymph
nodes (mesenteric), mammary glands, nasal cavity andturbinates, oral cavity, ovaries, pancreas, parathyroids,
pharynx, pituirary, preputial gland, prostate, salivary
glands, scrotal sac, seminal vesicles, skin, small intestine(duodenum, ileum, jejunum), spleen, stomach, testes, thymus,
thyroid, tongue, trachea, tunica vaginalis, urinary bladder,uterus and Zymbal's glands.Target organs and gross lesions
were examined at lowere doses until a no-observed chemical
effect was determined. Target organs included the following:
nasal epithelium, bone marrow, forestomach, oesophagus,
thyroid and uterus. Organ weights recorded for brain, liver,right kidney, thymus, heart, and lungs of all animals, andthe right testis of all males.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test
mean compound consumption (mg/kg bw/day):males
females0 ppm
00300 ppm
26
271000 ppm
90
95
3000 ppm
261
268
10000 ppm
877
886
30000 ppm
2600
2570
All rats survived.
30000 ppm: Body weight gain was significantly reduced inmales and females, feed consumption was depressed during
the first week, all rats had thin appearance by day 6 notbeyond d 7.

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ID: 15831-10-4
DATE: 24.05.2004
At study termination, weights (w) were sign. increased:
brain (males: rel. w. at 30000 ppm, p</=0.01)), right kidney(males: rel. w. from 10000 ppm, p</=0.05); females: abs. andrel. from 10000 ppm, p</=0.05), liver (males: rel. from 3000
ppm, p</=0.05 and absol. at 10000 ppm, p</=0.05; females:
rel and absol. w. from 1000 ppm, p</=0.05), and rel righttestes weight in males at 30000 ppm (p</=0.01).
No gross lesions were noted at necropsy.
Microscopically no changes were reported from brain, liverand kidney.
Microscopically changes: (avarage severity score based on ascale of 1 to 4 (1=minimal. 2=mild, 3=moderate, 4=marked),
contr., low to high dose):
respiratory epithelium in the nasal cavity (hyperplasia:
males, 0/5, 0/5, 0/5, 5/5[2.0], 5/5[2.4], 5/5[3.2]; female,
0/5, 0/5, 3/4[1.0], 5/5[1.6], 5/5[1.6], 5/5[2.8]),
thyroid gland (increased colloid in the follicles: males,
0/5, low dose: not performed, 0/5, 3/5[1.0], 5/5[1.0],
5/5[1.8]; female,1/5[1.0], low dose not performed, 0/5[1.0],
4/5[1.0], 5/5[1.8], 4/5[3.2], the biological significance is
uncertain (not noted with the individual isomers,nor
associated with overt follicular cell hypertrophy and/or
hyperplasia),
oesophagus (hyperplasia and hyperkeratosis of theepithelium: males, females, minimal from 3000 ppm),
forestomach (hyperplasia of the epithelium: males, females,
minimal from 10000 ppm; females, minimal hyperkeratosis from10000 ppm)
and bone marrow (hypocellularity: males, minimal from 30000
ppm; females, minimal from 10000 ppm)
local toxicity: NOAEL(male, female): 300 ppm
systemic toxicty: NOAEL(male, female): 1000 ppm(1) valid without restriction
Critical study for SIDS endpoint

Reliability
Flag02.05.2003

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses
Control group
NOAEL
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:
:
:
:
:
:

Sub-acutemouse
male/female
B6C3F1oral feed
28 dcontinuously in feed
no0, 300, 1000, 3000, 10000, 30000 ppm (see RM)
yes, concurrent no treatment
300 ppmother: EPA OTS 7952600
1991
yesother TS: m-/p-cresol (60%:40% mixture)

Method:SIZE OF STUDY GROUP:
5 male and 5 female mice per group
TIME HELD BEFORE STUDY: 13-15 days
METHOD OF ANIMAL DISTRIBUTION:
randomized for each sex on the basis of body weight into
groups per sex
DIET: NIH-07 mouse ration
ANIMAL ROOM ENVIRONMENT:

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ID: 15831-10-4
DATE: 24.05.2004

Remark:Result:temperature: 72° +/-3° F, humidity: 50 % +/-15 %,Fluorescent light: 12 hrs/day, room air changes : 10-12
changes/hr
TYPE AND FREQUENCY OF OBSERVATION:
observed twice daily, body weight taken initially, weekly,
and at termination, feed consumption by cage recorded twice
weeklyNECROPSY AND HISTOLOGIC EXAMINATION:
necropsy and tissue collection performed for all animals. A
complete histopathologic examination was conducted on allcontrol animals, all animals in the highest dose group withat least 60 % survivors at study termination, and allaninmals in higher dose groups inclusive of early deaths.
The following organs and/or tissues were included incomplete histopathological examinations, as well as any
tissue masses, gross lesions, and associated regional lymph
nodes: adrenals, aorta, bone (sternebrae, femur, orvertebrae, including marrow), brain, bronchi, clitoral
gland, epididymis, oesophagus, gallbladder, heart, kidney,large intestines (caecum, colon, rectum), liver, lungs,
lymph nodes (mesenteric), mammary glands, nasal cavity andturbinates, oral cavity, ovaries, pancreas, parathyroids,
pharynx, pituitary, preputial gland, prostate, salivary
glands, scrotal sac, seminal vesicles, skin, small intestine(duodenum, ileum, jejunum), spleen, stomach, testes, thymus,
thyroid, tongue, trachea, tunica vaginalis, urinary bladder,uterus and Zymbal's glands. Target organs and gross lesions
were examined at lower doses until a no-observed chemical
effect was determined. Target organs included the following:
nasal epithelium, bone marrow, forestomach, oesophagus, lungand uterus and ovaries. Organ weights recorded for brain,
liver, right kidney, thymus, heart, and lungs of all
animals, and the right testis of all males.
STATISTICAL METHODS:
nonparametric multiple comparison test of Dunn and Shirley,
Jonckheere's test
mean compound consumption (mg/kg bw/day):males
females0 ppm
00300 ppm
50
651000 ppm
161200
3000 ppm
471
604
10000 ppm
1490
1880
30000 ppm
4530
4730
No effect on survival;
clinical signs of toxicity in males and females: alopecia,
dehydration, hunched posture, hypothermia, lethargy, roughhair coat, thin appearance.
30000 ppm, males, females: weight loss; decreased feed
consumption during the first week and during the third week
(females only);
30000 and 10000 ppm: sign. decreased weight gain,
At study termination weights (w) were sign. increased:
brain (male, female: abs. and rel. w at 30000 ppm,p</=0.01), right kidney (male: abs. w at 30000 ppm,p</=0.01; female: rel. w at 30000 ppm, p</=0.05), liver(male: rel. w from 1000 ppm, p</=0.05; female: rel. and abs.
w from 3000 ppm, p</=0.05) and right testes in males at
30000 ppm (p</=0.01)
No gross lesions were observed at necropsy.
Microscopically no changes were reported from brain, kidney

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DATE: 24.05.2004
and liver.
Microscopic changes which were characterized by average
severity score based on scale of 1 to 4 (1=minimal, 2=mild,
3=moderate, 4=marked) were reported fromnose (contr., low dose to high dose, respiratory epithelium
hyperplasia: male, 0/5, 300 and 1000 ppm: not performed,
0/5, 1/5[1.0], 5/5[1.6]; female, 2/5[1.5], low dose: notperformed, 0/5, 3/5[1.0], 3/5[1.7], 4/5[1.5]; olfactorium
epithelium: at 30000 ppm, male, atrophy 2/5[1.0] andrespiratory metaplasia 3/5 [1.3]; female, olfactory
epithelium respiratory metaplasia at 30000 ppm, 2/5[1.0]),lung (bronchiolar hyperplasia, minimal in males and females
at 30000 ppm),
oesophagus (males, minimum hyperplasia and hyperkeratosis at
30000 ppm),
forestomach (males, at 30000 ppm, minimal hyperplasia of thesquamous epithelium),bone marrow (minimal hypocellularity at 30000 ppm),
atrophy of the ovary (mild) and uterus (moderate) at 30000
ppm

Reliability
Flag
05.02.2004

:
:

Type
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Post exposure period
Doses

:
:
:
:
:
:
:
:
:

Control group
MethodYear
GLP
Test substance

:
:
:
:
:

Method:Result:Reliability:

local toxicity:
NOAEL(male): 3000 ppm; NOAEL(female): 1000 ppm systemic
toxicity:
NOAEL(male): 300 ppm; NOAEL(female): 1000 ppm(1) valid without restriction
Critical study for SIDS endpoint(101)
Sub-acutemouse
male/female
CD-1
oral feed
14 d
daily
no
0, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0 % (target dose: 0, 375, 750, 1500, 2250,
3000, 4500 mg/kg bw)
yes, concurrent no treatment
other: NTP continuous breeding protocol, task 1 see freetext ME
1990
yesother TS: m-/p-cresol (60%/40%)
48 male and 48 female mice: 8 per sex per dose, datacollected included clinical signs, individual body weights,
feed and water consumption, mortality data
mortality:
3.0 %-gr.: 1/8 (12.5 %) males, 1/8 (12.5 %) females (due toindeterminant causes)
Clinical signs:
all mice in 3.0 %-, and some in 2.0 %- and 1.0 %-group:
lethargy, hunched back, squinted eyes, rough coatdose related reduced feed consumption, water consumption andreduced body weight gain
3 %-group: sign. terminal weight loss of males and females(2) valid with restrictions
preliminary dose range finding study for the two generation
reproductive study: see also chapter 5.8.1

04.09.2002

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5.5

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

GENETIC TOXICITY ‘IN VITRO‘

Type
System of testing
Test concentration
Cycotoxic concentr.
Metabolic activation
Result
MethodYear
GLP
Test substance

:
:
:
:
:
:
:
:
:
:

Ames test
Salmonella typhimurium TA 97, TA98, TA100, TA 1535
0, 10, 33, 100 333, 1000, 3333 , 6666 ug/plate dissolved in DMSOHigh dose was limited by toxicity or solubility
with and without
negative
other: EPA OTS 798.5265, see also fretext ME
1990
yesother TS: m/p-cresol (60/40),

Method:RemarkReliability

:
:

Flag
05.02.2004:

detailed protocol in Zeiger 1988 Environ. Molec. Mutagen. 11 (Suppl.12), 1158: The metabolic activation system was prepared from Aroclor 1254induced male Sprague-Dawley rat and male Syrian hamster livers, andused as 10% or 30% concentrations
SOLVENT: DMSOCONTROL. DMSO and 2-aminoanthracene, 4-nitro-o-phenylenediamine,
sodium azide, 9-aminoacridine served as negative and positive controls,
respectively.
The positive control was functional.
(2) valid with restrictions
only 4 strains were used
Critical study for SIDS endpoint
(101)

5.6

GENETIC TOXICITY ‘IN VIVO‘

TypeSpecies
Sex
StrainRoute of admin.
Exposure period
Doses

:
:
:
:
:
:
:

Result
MethodYear
GLP
Test substance

:
:
:
:
:

Method:RemarkResult::Reliability:

Flag
16.12.2002:

Micronucleus assay
mouse
male/female
B6C3F1oral feed
13 weeks
0, 625, 1250, 2500, 5000, 10000 ppm (approx. m: 0,96, 194, 402, 776,
1513mg/kg bw; f: 116, 239, 472, 923, 1693 mg/kg bw)
negative
other: see ME
1990
yesother TS: m/p-Cresol: 60:40
10 mice/sex/dose treated for 13 weeks (see also Chapter 5.4)
at termination smears were prepared from blood sampled bycardiac puncture from control and dosed mice: 10000
normochromatic erythrocytes from each mice scored for
micronuclei
for signs of toxicity see chapter 5.4
No significant elevation in the frequency of micronucleatederythrocytes was observed in either male or female mice(2) valid with restrictions
not fully in accordance with the guideline, e.g. no positive
control
Critical study for SIDS endpoint(101)

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ID: 15831-10-4
DATE: 24.05.2004

Type
Species
Sex
StrainRoute of admin.
Exposure period
Doses
Result
Method

:
:
:
:
:
:
:
:
:

Year
GLP
Test substance:::

ResultReliability

:
:

other
Drosophila melanogasterno dataother: Berlin - Wild Type eggs
other: see method
other: see method
other: see method
negative
other: Isolated ovaries of Berlin wild Typ Drosophila melanogaster weretreated with cresol (1:10^3) for 15 min and then implanted into a host. The
chromosomes of the descendants were examined.
1949
noother TS: no datano mutations were found.
(4) not assignableunusual test method

23.10.2002
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CARCINOGENICITY

17.06.2002
17.06.2002
5.8.1

TOXICITY TO FERTILITYType: other: Reproductive Assessment by Continuous breeding (RACB)Species: mouseSex: male/female
Strain: CD-1
Route of admin.
: oral feed
Exposure period: 14 w
Frequency of treatm.
: continuously in dietPremating exposure period
Male
: 7d
Female : 7 dDuration of test
: 41 w
No. of generation: 2
studies
Doses: 0, 0.25, 1.0, 1.5 % (target dosage: 0, 375, 1500, 2250 mg/kg bw/day)Control group: yes, concurrent no treatment
NOAEL parental: .25 %
other: NOAEL (Fertility : 1 %F0, F1)
Method: other: NTP 2 generation continuous breeding protocol, see freetext ME
Year: 1990GLP: yes
Test substance: other TS: m-/p-cresol (60%:40% mixture)
Method364:

NTP continuous breeding protocol:
Task 1:dose-finding, see Chapter 5.4
Task 2:
reproduction and fertility study: 20 ps/group, 40 ps

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

Resultm- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004:(contr.); exposure period, F0: 7d prior to cohousing, 98 d
(14 w) of continuous breeding, then pairs were seperated andany litters born after the final litter were reared by thedams until weaning, at the end of week 15: evaluation ofclinical signs, parenteral bw, fertility (number producing alitter/number of breeding pairs), litters per pair, live
pups per litter, proportion of pups born alive, sex of live
pups, pup body weights within 24 hrs of birth, feed andwater consumption.
Task 3:determination of the affected sex only when pos. effects on
reproductive function during task 2:
one week crossover mating trial with parental mice fromcontrol and high dose groups, vaginal cytology evaluationfor 12 d prior to sacrifice; low dose and mid dose mice were
hold for necropsy together with task 3 mice: body and organ
weight determination and sperm evaluation of all males.
Task 4:
offspring assessment: mice born after week 15 were kept
until maturity and cohabited for 7 d and housed singly untildelivery, collection of vaginal smears, body and selctedorgan weights, epididymal and testicular spermatozoa
evaluation, mating index, pregnancy index, fertility index,
live F2 pups per litter, proportion of F2 pups born alive,
sex ratio, live F2 pup weight, adjusted live F2 pup weight,
average dam weight, average number of days to litter
Statistical methods:
Test for linear trend: ANOVA
Turkey's test for pairwise compairison to controls
nonparametric multiple comparison procedures of Dunn andShirley as modified by Williams
Jonckheere's test
Cochran-Annitage test
Chi-square test
parametric analysis of covarianceF-test,Dunn's test
F0:
mortality:
7 mice died: 2 in the controlgr., 2 in the 1.5 % dose-gr., 1
in the 1.0 %-dose-gr., 2 in the 0.25 %-dose-gr.
1.0 and 1.5 %-group:
reduced body weight gain and feed consumption after 16 w,
especially in delivering and lactating dams
1.5 %-group:
decreased bw, increased liver and kidney weight
all mice:
reproductive competence was not affected, including inital
fertility, the proportion of pups born alive or the sex of
the pups born alive,
1.5 % -group:
adjusted live pup weight and the number of pups per litter(both sexes) were decreased by 5% and 20%, respectively;
cumulative days to fifth litter were increased by almost 3 dcompared to control
1.5 %-group, males:
decreased epididymal and seminal vesicle weights by 10 and
21 %, respectively, but no change in testis weight, sperm
parameters or testicular and epididymal histology
Cross over mating did not clearly reveal the affected sex,

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as the only parameter affected (adjusted live pup weight)
was decreased if either sex was dosed.
F1-pups: 1.5 %-group:birth weights decreased by 5 %, decreased preweaning growthby 26 % and postweaning survival decreased by 39 %clinical signs: reduced size, dehydratation, lethargy, roughcoat
F1-adults:
no effect on reproductive performance:
1.0 and 1.5%-group, male:decreased bw, decreased reproductive organ weights(prostate, seminal vesicles, testes), but no effects onsperm parameters or histology, increased relative liver andkidney weights
1 and 1.5 %-group, female:terminal bw reduced
0.25-, 1.0-, and 1.5 %-group, female:ovarian weight reduced, kidney- and liver-weights increased
no effect of treatment on oestrous cyclicity and ovarian orliver and kidney histology

Reliability
Flag
05.02.2004
5.8.2

:
:

NOAEL(F0, F1, general toxicity): 0.25 %, based on
differences in bw and organ weights to the concurrent
controls.
Reproductive competence of F0, F1-generation was notaffected by treatment.
NOAEL(fertility, F0, F1): 1 %F0-generation 1.5 % - group: decreased adjusted live pups
weights, decreased number of live pups per litter andincrease of the cumulative days to the fifth litterF1 generation 1.5 % -group: live pup weights and adjusted
live pup weights reduced.
(1) valid without restriction
Critical study for SIDS endpoint(102)

DEVELOPMENTAL TOXICITY/TERATOGENICITY

19.06.2002
5.8.3

TOXICITY TO REPRODUCTION, OTHER STUDIESType
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result

366

:
:
:
:
:
:
:
:
:
:
:
:

other:
In vivoratmale/female
other: F344/N
oral feed
13 w
daily
13 w
0, 1880, 7500, 30000 ppm
yes, concurrent no treatment
See freetext RS

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Method:Year
GLP
Test substance:::

RemarkResult::Reliability
Flag
16.12.2002

:
:

Type
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses
Control group
Result
Method

:
:
:
:
:
:
:
:
:
:
:
:
:

Year
GLP
Test substance

:
:
:

other
In vivo
mouse
male/female
B6C3F1oral feed
13 w
daily
13 w
0, 625, 2500, 10000 ppm
yes, concurrent no treatment
No findings
other: determination of sperm motility and concentration in males andlength of oestrus cycle and vaginal cytology following repeated dose
according EPA OPP 82-1
1991
yesother TS: m-/p-cresol (60%:40% mixture)

RemarkReliability
Flag
18.06.2002:::

see also chapter 5.4.
(1) valid without restriction
Critical study for SIDS endpoint

Type
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses

:
:
:
:
:
:
:
:
:
:

Control group
Result::

MethodYear
GLP
Test substance

:
:
:
:

other: determination of sperm motility and concentration in males andlength of oestrus cycle and vaginal cytology following repeated dose
according EPA OPP 82-1
1991
yesother TS: m-/p-cresol (60%:40% mixture)
see also chapter 5.4.
males:
no difference to the respective controls in weights of righttesticle, right epididymis, right epididymal tail, nodifference in the concentration of viable sperm, only slightbut sign. reduced sperm motility at 30000 ppm
females: increased oestrus cycle length from 7500 ppm(1) valid without restriction
Critical study for SIDS endpoint
(101)

(101)
other
In vivoratmale/female
other: F344/N
oral feed
28 dcontinuously in feed28 d0, 300, 1000, 3000, 10000, 30000 ppm (m: 0, 26, 90, 261, 877, 2600 mg/kg
bw; f: 0, 27, 95, 268, 886, 2570 mg/kg bw)
yes, concurrent no treatment
male, 30000 ppm: increased right testes weight without histopathologic
correlateother: description in chapter 5.4
1991
yesother TS: m/p-cresol (60%:40% mixture)

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m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Reliability
12.11.2002:

Type
In vitro/in vivo
Species
Sex
StrainRoute of admin.
Exposure period
Frequency of treatm.
Duration of test
Doses

:
:
:
:
:
:
:
:
:
:

Control group
Result::

MethodYear
GLP
Test substance

:
:
:
:

other
In vivo
mouse
male/female
B6C3F1oral feed
28 dcontinuously in feed28 d0, 300, 1000, 3000, 10000, 30000 ppm (m: 0, 50, 161, 471, 1490, 4530
mg/kg bw; f: 0, 65, 200, 604, 1880, 4730 mg/kg bw)
yes, concurrent no treatmentm, 30000 ppm: increased testes weight without histopathologic correlate; f,
30000 ppm: atrophy of ovaries and uterusother: see chapter 5.4.
1991
yesother TS: m/p-cresol (60%:40% mixture)

Reliability
05.09.2002:(1) valid without restriction(1) valid without restriction
(101)

(101)

5.9

SPECIFIC INVESTIGATIONS

5.10

EXPOSURE EXPERIENCE

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:368

Case Report: Muenchhausen's Syndrome with multiple skinulcers caused by cresol is the diagnosis resulting from thefindings of a 25 years old female nursing student.
(4) not assignable(104)
It is reported that mortality from bladder cancer wasincreased among molders in the foundry industry. The author
suggest that cresols might act as tumour promotor.
(4) not assignable(105)
It is reported that 2 patients with chronic exposure to
cresol or creosote developed multifocal transitional
carcinoma of the bladder with muscle invasion.
(2) valid with restrictions(106)
Case Report: A 52 year old man attempted to commit suicide
by ingesting approximately 100 ml of penetrating oil, apetroleum distillate containing 85% kerosine, 12% mixed
cresols, 2% surfactant and 1% artificial colour. He revealeda massive intravascular Heinz-body hemolytic anemia
associated with the presence of bizarre-looking
erythrocytes. He was treated successfully.

UNEP PUBLICATIONSOECD SIDS
5. TOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:

Remark:Reliability
16.01.2003:(2) valid with restrictions(107)
Case Report: A 74 old widow died after ingestion of an
overdose of lysol. Post morten findings: lower third of theoesophagus and the whole of the stomach lining were bleached
white, areas of mucosal desquamation, pylorus and duodenum
showed a marked degree of congestion; 30.4 mg/100 ml mixed
cresols in the urine, 48.0 mg/100 g mixed cresols in theliver; 19.0 mg/100 ml mixed cresols in the blood.
(2) valid with restrictions(108)
A 76 year old unmarried woman swallowed an unknown quantityof lysol. She was found shortly afterwards unconscious, anddespite resuscitative measures, she died within 2 hours;
post mortem findings: oesophagus, denuded of mucosa, wasdeep purple; stomach dilated, containing 500 ml chocolate coloured fluid, mucosa: dark brown, necrotic; small
perforations on the anterior gastric wall; trachea andbronchi with mucosal oedema, lungs congested; 90 mg mixed
cresols/100 g liver; 39.6 mg mixed cresols/100 g kidney ;7.1 mg mixed cresols/100 ml blood.
(2) valid with restrictions(108)
Case report: A 46 year old labourer, working in a chemicalfactory, had a cresol solution poured over his upper trunk
when he was transporting a tub containing hot cresol. The
lesion consisted of a light brown eschar with well-defined
margine, minimal oedema. He developed gross haemeturia,
oliguria and finally anuria within 24 h, uppergastrointestinal bleeding within 2 days, on day 4
progressive dyspnoe and tachypnoe, hypertension with bloodpressure arround 200/100 mmHg during the first 10 days. On
day 15 he developed a septic shock with severe jaundice andrenal failure. He was treated successfully and discharged on
day 38 after injury.
(2) valid with restrictions(109)
Case Report: A man (50 years old) has drunk cresol solution
to commit suicide. 2 hours later he was found to beunconscious, cyanotic with methemoglobinemia, blood pressure
90-136 mm Hg; pulse 101/min; light reflex: slow; urine
colour: black brown. Methb increased in the patients blood
drastically within 15 hours. He was treated successfully.
(2) valid with restrictions(110)
Workers exposed to organic solvents (i.e. cresol) showed
increased levels of cresol, hippuric acid and phenols inurine and decreased levels of albumiun and delta-globulin in
the serum.
(4) not assignable(111)

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5. TOXICITY

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004

Remark:Reliability
16.01.2003:

RemarkReliability
16.01.2003

:
:

5.11

There are several human case studies reporting the use of
Lysol, a cresol-containing solution, as an abortificant. In
addition, intravaginal application of Lysol produces
extensive hemolysis, erosion of blood vessels, kidney
tubular damage, liver necrosis and death.
(4) not assignable(112) (113)
The probable oral lethal dose for humans is 50-500 mg/kg bw(2) valid with restrictions(114)

ADDITIONAL REMARKS

Type

:

other

Remark:Reliability
16.01.2003:

0.2% Formocresol, containing 35% cresol and 19%
formaldehyde, causes the cell death of 50% of the treatedHela cells within 4 hours.
(4) not assignable

370

(115)

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(1)

ACGIH. 2000. TLVs and BEIs. American Conference ofGovernmental Industrial Hygienists (ACGIH), 1330 Kemper
Meadow Drive, Cincinnati, Ohio 45240-1634(2)

ACGIH.. 2000. TLVs and BEIs. American Conference ofGovernmental Industrial Hygienists (ACGIH), 1330 Kemper
Meadow Drive, Cincinnati, Ohio 45240-1634(3)

Deutsche Forschungsgemeinschaft, MAK- und BAT-Werte-Liste
2001, Senatskommission zur Prüfung gesundheitsschädlicher
Arbeitsstoffe, Mitteilung 37, VCH Verlagsgesellschaft mbH,
Weinheim 2001.

(4)

INRS, Valeurs limites d'exposition professionnelle aux
substances dangereuses de l'ACGIH aux Etats-Unis et de laCommission MAK en Allemagne, Cah. Notes Doc. 1992, 147,
195-225.

(5)

Bayer AG, Safety Data Sheet (2001-07-31)(6)

Hansch C, Leo AJ (1981) Medchem Project Issue No. 19, Claremont, CA Pomona College(7)

Bayer AG (2003), internal report on water solubility(8)

Semadeni M, Stocker DW, Kerr JA (1995) Int. J. Chem. Kinet.
27, 287-304(9)Atkinson R (1994) J. Phys. Chem. Ref. Data, Monograph No.2:
Gas-Phase Tropospheric Chemistry of Organic Compounds(10)

Atkinson R and Aschmann SM (1990) Int. J. Chem. Kinet. 22:
59-67

(11)

Atkinson R (1987) Intern. J. Chem. Kinet. 19: 799-828(12)Atkinson R, Darnall KR, Lloyd AC, Winer AM, Pitts JN (1979)
Adv. Photochem. 11: 375-488(13)

Atkinson R, Darnall, KR, Pitts, JN (1978) J. Phys. Chem. 82:
2759 - 2761

(14)

Koch R and Wagner BO (1989) Umweltchemikalien. VCH
VerlagsGmbH, Weinheim, 191-193(15)

Freitag D, Ballhorn l, Geyer H, Korte F (1985) Environmental
Hazard profile of organic chemicals. Chemosphere 14:
1589-1616(16)

Evangelista RA, Allen HL, Mandel RM (1990) J. Hazard. Mater.
25(3): 343-360(17)

Aelion CM, Swindoll CM, Pfaender FK (1987) Adaptation to andBiodegradation of Xenobiotic Compounds by Microbial
Communities from a Pristine Aquifer. Appl Environm Microbiol
53: 2213-2217(18)

Hawthorne SB and Sievers RE (1984): Environ Sci Technol 18,
483-490. As cited in HSDB (1993)

UNEP PUBLICATIONS

371

OECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(19)

Altschuh J, Brueggemann R, Santl H, Eichinger G, Piringer OG (1999) Henry's Law
Constants for a Diverse Set of Organic Chemicals: Experimental Determination andComparison of Estimation Methods. Chemosphere 39: 1871 - 1887

(20)

Boyd SA (1982) Soil Sci. 134(5): 337-343(21)

Bayer AG (2002): calculation of the environmental
distribution of m-cresol according to fugacity model Mackay
level I

(22)

Bayer AG (2002) Ready Biodegradability: Closed Bottle Test

(23)

Desai S, Govind R, Tabak H (1990) ACS Symp Ser 422: 142-156(24)

Wellens H (1990) Z Wasser Abwasser Forsch 23: 85-98(25)

Pitter P (1976) Determination of biological degradability oforganic substances. Water Research 10: 231-235(26)

Shelton DR, Tiedje JM (1981) Development of test for
determining anaerobic biodegradation potential. NTIS Report[PB 84-166495], Springfield(27)

Shelton DR, Tiedje JM (1984) Appl. Environ. Microbiol. 47:
850-857(28)

Battersby NS and Wilson V (1989) Appl. Environ. Microbiol.
55: 433-439(29)

Liu D, Pacepavicius G (1990) Toxicity Assessment 5 (4):367-387(30)

Jensen BK, Arvin E, Gundersen, AT (1989) Biodegradation ofphenolic compounds and monoaromatic hydrocarbons by a mixed
wastewater culture under denitrifying conditions. In:
Quaghebeur D, Temmermann I, Angeletti G (Ed.), Organic
contaminants in waste water, sludge and sediment:
occurence, fate and disposal. London, 150-157(31)

Boyd SA, Shelton DR, Berry D, Tiedje JM (1983) Appl.
Environ. Microbiol. 46: 50-54(32)

Fedorak PM and Hrudey SE (1984) Water Res 18: 361-7(33)

Roberts DJ, Fedorak PM, Hrudey SE (1987) Can. J. Microbiol.
33, 335-338(34)

Horowitz A, Shelton DR, Cornell CP, Tiedje JM (1982) Dev.
Ind. Microbiol. 23, 435-444(35)

Wang Y-T, Suidan MT, Pfeffer JT, Najam I (1989) Biotechnol.
Bioeng. 33: 1353-1357(36)

Smolenski WJ and Suflita JM (1987) Appl. Environ. Microbiol.
53: 710-716(37)

Kaminski U, Kuschk P, Janke D (1990) J. Basic Microbiol. 30:
259-265

372

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(38)

Kondo M, Nishihara T, Shimamoto T, Koshikawa T, Ito T,
Sawamura R, Tanaka K (1988) Eisei Kagaku 34(2): 188-185(39)

Arvin E, Jensen B, Godsy EM, Grbic-Galic D (1989) Microbial
degradation of oil and creosote related aromatic compounds
under aerobic and anaerobic conditions. Int. Conf.
Physiochem. Biol. Detoxif. Hazard. Wastes 2: 828-847(40)

Ramanand K and Suflita JM (1990) Anaerobic biodegradation of
m-cresol in anoxic aquifer slurries and a sulfate reducing
bacterial enrichment. Abstracts Annu. Meet. Amer. Soc.
Microbiol. 90, 299(41)

Roberts DJ, Fedorak PM, Hrudey SE (1990) Appl. Environ.
Microbiol. 56: 472-478(42)

DeGraeve GM, Geiger DL, Meyer JS, Bergman HL. (1980) Acuteand embryo-larval toxicity of phenolic compounds to aquaticbiota. Arch. Environ. Contam. Toxicol. 9: 557-568(43)

Howland, R.M.. Investigations in Fish Control 34, 1-10,
US Department of the Interior, Bureau of Sport Fisheries
and Wildlife (1969)(44)

Saarikoski J and Viluksela M (1982) Ecotox. Environ. Safety
6: 501-512(45)

Wellens H (1982) Z. Wasser Abwasser Forsch. 15: 49-52(46)

Falk-Petersen IB, Kjorsvik E, Lonning S, Moller Naley A,
Sydnes LK (1985) Sarsia 70, 11-16(47)

Ruebelt C et al. (1982) Schadstoffe im Wasser. Band II,
Phenole. Boldt Verlag, Boppard, S. 101-115(48)

European inland fishery advisory commission, working party
on water quality criteria for European fresh water fish,
Water Res. 7, 929-941 (1973).

(49)

Dietz F and Traud J (1978) GWF-Wasser/Abwasser 119, 318-325(50)

Portman JE and Wilson KW (1971) The toxicity of 140
substances
to the brown shrimp and other marine animals. Ministry ofagriculture, fisheries and food, Fisheries Lab. Shellfish
Inf. Leafl. no. 22: 1-11

(51)

Jones, H.R., Environmental control in the organic andpetrochemical industries. Noyes Data Corp. (1971).
Cited in: Verschueren, K., Handbook of environmental dataon organic chemicals. Van Nostrand Reinhold Co., New York,S. 406-408 (1983)(52)

Yoshioka Y, Mizuno, T, Ose, Y, Sato, T (1986) Chemosphere15(2): 195-203(53)

Juhnke I and Luedemann D (1978) Z. Wasser Abwasser Forsch.
11: 161-164

UNEP PUBLICATIONS

373

OECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(54)

Vind, H.P. & Hochman, H., Toxicity of chemicals to marine
borers - 1. Interim report (technical report 048). US Naval
Civil Eng. Lab., Port Hueneme, 1-134 (1960)(55)

Bringmann G and Kuehn R (1982) Z. Wasser Abwasser Forsch.
15: 1-6(56)

Bringmann G and Kuehn R (1977) Z. Wasser Abwasser Forsch.
10: 161-166(57)

Devillers J (1987) Chemosphere 16: 1149-1163(58)

Devillers J (1988) Sci. Total Environ. 76: 79-83(59)

Parkhurst BR, Bradshaw AS, Forte JL, Wright GP (1979) Bull.
Environ. Contam. Toxicol. 23: 349-256(60)

Bringmann G and Kuehn R (1959) Gesund.-Ing. 80: 115-120(61)

Verschueren, K., Handbook of environmental data on organic
chemicals. 2nd Ed., Van Nostrand Reinhold Co., New York, S.
406-408 (1983)(62)

Bringmann G and Kuehn R (1977) Z. Wasser Abwasser Forsch.
10: 87-98(63)

Huang JC and Gloyna EF (1968) effect of organic compounds on photosynthetic
oxygenation 1. Chlorophyll destruction and suppression of photosynthetic oxygen
production. Water Res 2: 347-366(64)

Bringmann G (1975) Gesund.-Ing. 96: 238-241(65)

Bringmann G and Kuehn R (1976) GWF-Wasser/Abwasser 117:
410-413(66)

Nobel W, Mayer T, Kohler A (1983) Z. Wasser Abwasser Forsch.
16(3): 87-90(67)

Pulich WM Jr, Winters K, Van Baalen C (1974) Mar. Biol. 28,
87-94

(68)

Robinson JM, Allen BE, Denton TE (1976) Cresol induced
growth inhibition in cultures of chick fibroblasts andankistrodesmus. J Alabama Acad Sci 47: 243-246(69)

Klecka GM and Landi LP (1985) Chemosphere 14 (9): 1239-1251(70)

Tomlinson TG, Boon AG, Trotman CNA (1966) J. Appl. Bact. 29(2): 266-291(71)

Liu D (1985) Environ. Contam. Toxicol. 34: 331-339(72)

Blum DJW and Speece RE (1991) Research Journal WPCF 63 (3):198-207(73)

Warne MSJ, Connell DW, Hawker DW (1989) Chemosphere 19,1113-1128(74)

Warne MSJ, Connell DW, Hawker, DW (1989) Wat. Sci. Tech. 21:
135-139

374

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(75)

Bringmann G, Kühn R, Winter A (1980) Z. Wasser Abwasser
Forsch. 13: 170-173(76)

Bringmann G (1978) Z. Wasser Abwasser Forsch. 11: 210-215(77)

Schultz TW, Kyte LM, Dumont JN (1978) Arch. Environm.
Contam. Toxicol. 7: 457-463(78)

Bringmann G and Kuehn R (1980) Z. Wasser Abwasser Forsch. 1:
26-31

(79)

Bitton G (1983) Bacterial and Biochemical Tests forAssessing Chemical Toxicity in the Aquatic Environment: A
Review. Crit Rev Environ Control 13: 51 -67(80)

Hartung J (1987) Toxicity Assessment 2 (1): 1-15

(81)

Lebsack ME, Anderson AD, DeGraeve GM, Bergman HL (1981)
Aquatic Toxicology and Hazard Assessment: Fourth Conference,
ASTM STP 737, D.R.Branson and K.L. Dickson, Eds., American
Society for Testing and Materials: 348-356(82)

Palmer LM, Baya AM, Grimes DJ, Colwell RR (1984) FEMS
Microbiol. Lett. 21: 169-173(83)

Palmer LM, Baya AM, Xu HS, Grimes DJ (1983) Amer. Soc.
Microbiol., Abstract Ann. Meet., p. 276(84)

Cho, K.-Y. et al., Korean J. Appl. Microbiol. Bioeng. 17,
236-240 (1989)(85)

Kanne R, Rast HG, Springer W (1986) Analytik
bakterientoxischer Effekte mit Hilfe genetisch konstruierter
Leuchtbakterien. Z Anal Chem 325 (1): 136 - 139(86)

Loveless LE, Spoerl E, Weisman TH (1954) J. Bacteriol. 68:
637-644(87)

Bringmann G and Kuehn R (1960) Ges.-Ing. 81 (11): 337-339(88)

Hulzebos EM, Adema DMM, Dirven-van Breemen, Henzen L, vanDis, WA, Herbold, HA, Hoekstra JA, Baerselman, R, van Gestel
CAM (1993) Environ. Toxicol. Chem. 12 (6): 1079-1094(89)

Yatagai M and Unrinin G (1989) Mokuzai Gakkaishi 35,
1021-1028(90)

Schafer EW Jr, Bowles WA Jr, Hurlbut J (1983) Arch.
Environm. Contam. Toxicol. 12: 355-382(91)

Layiwola PJ, Linnecar, DFC, Knights B (1983) Xenobiotica 13:
107-113(92)

Schroth MN and Hildebrand DC (1968) Phytopathol. 58, 848-854(93)Leach FR, VanDoren SR, Frazier LB, Hall MS (1983)
Development of a cell culture screen for water toxicity(NTIS report no. PB83-220533). Oklahoma State Univ.,
Stillwater

UNEP PUBLICATIONS

375

OECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(94)

vanDoren SR, Hall MS, Frazier LB, Leach FR (1984) A
rapid-cell culture assay of water quality. Bull Environ
Contam Toxicol 32: 220-226(95)

Deichmann WB and Keplinger ML (1981) Phenols and phenolic
compounds. In: Clayton GD and Clayton FE (Ed.) Patty's
industrial hygiene and toxicology. 3rd rev ed Vol 2A, Wileyand Sons, New York, 2597-2601(96)

IPCS (1995) (International Programme on Chemical Safety):
EHC (Environmental Health Criteria) No. 168: Cresols, WHO,
Geneva(97)

Mandel H.G. (1971) Pathways of Drug Biotransformation:
Biochemical Conjugations in LaDu B.N., Mandel H.G. and Way
E.L. (eds.) Pathway of drug biotransformation: biochemical
conjugations, Williams and Wilkins, Baltimore, pp: 149-186(98)

Scheline Ronald R. (1973) Metabolism of foreign compounds bygastrointestinal microorgamisms, Pharmacological Reviews 25,
451-523(99)

Younger Laboratory (1974) Skin irritation in albino rabbits
after application of o-, m- and p-cresol, at the request of
Productol Chemical Company, Whittler, California,
EPA/OTS0517499(100)

DECOS (Dutch Expert Committee on Occupational Standards)
1998, cited in: Deutsche Forschungsgemeinschaft, MAK- und
BAT-Werte-Liste 2001, Senatskommission zur Prüfung
gesundheitsschädlicher Arbeitsstoffe, Mitteilung 37, VCH
Verlagsgesellschaft mbH, Weinheim 2001.

(101)

NTP (1992) Toxicity studies of cresols (CAS Nos 95-48-7,
108-39-4, 106-44-5) in F344/N rats and B6C3F1 mice (feedstudies), NTP-Tox 9. Research Triangle Park, NC, U.S.
Department of Health and Human Services, Public HealthService, National Institutes of Health, National Toxicology
Program(102)

Research Triangle Inst (1992) Final report on the
reproductive toxicity of meta-/para-cresol in CD-1 Swiss
Mice, prepared for the National Toxicology Program, Research
Triangle Park, NC, PB 92-191741(103)

Hadorn E, Rosin S, Bertani G (1949) Ergebnisse der
Mutationsversuche mit chemischer Behandlung vonDrosophila-Ovarien in vitro. Hereditas (Suppl): 256-266(104)

Harada S, Nakanishi H, Nagae H, Takiwaki H, Arase S, Fukuda
Y (1991) Münchausen's syndrome with multiple skin ulcer
caused by cresol: a case report. Jap J Plastic Reconstruct
Surgery 34: 839-845(105)

Hansen ES (1991) Cancer mortality among danish molders. Am J
Ind Med 20: 401-409(106)

Garrett JS (1975) Association between bladder tumors andchronic exposure to cresol and creosote. J Occup Med 17: 492

376

UNEP PUBLICATIONSOECD SIDS
6. REFERENCES

m- / p-CRESOL MIXTURE
ID: 15831-10-4
DATE: 24.05.2004(107)

Cote MA, Lyonnais J, Leblond PF (1984) Acute Heinz-bodyanemia due to severe cresol poisoning: successful treatment
with erythrocytapheresis. Can Med Assoc J 130: 1319-1322(108)

Bruce AM, Smith H, Watson AA (1976) Cresol poisoning. Med
Sci Law 16: 171-176(109)

Lin CH and Yang JY (1992) Chemical burn with cresol
intoxication and multiple organ failure. Burns 18: 162-166(110)

Minami M, Katsumata M, Tomoda A (1990) Methemoglobinemia
with oxidized hemoglobins and modified hemoglobins found inbloods of workers handling aromatic compounds and in thoseof a man who drank cresol solution. Biomed Biochim Acta 49:
327-333(111)

Zawierta J and Machoy Z (1992) Zachowanie sie frakcji
bialkowych u ludzi eksponowanych na rozpuszczalniki
organiczne. Medycyna pracy 43: 183-186(112)

Presley JA and Brown WE (1956) Lysol-induced criminal
abortion. Obstet Gynecol 8: 368-370 cited in: EPA (1984)
Health effects assessment for cresols. PB 86-134616(113)

Vance BM (1945) Intrauterine injection of lysol as an
abortifacient. Report of a fatal case complicated by oil
embolism and lysol poisoning. Arch Pathol 40: 395-398 cited
in: EPA (1984) Health effect assessment for cresols. PB
86-134616(114)

Gleason MN, Gosselin RE, Hodge HC, Smith RP (1969) Clinical
toxicology of commercial products. Acute poisoning. thirded., The Williams & Wilkins Co., Baltimore, p. 42(115)

Spangberg L, Engström B, Langeland K (1973) Biologic effects
of dental materials. 3. Toxicity and antimicrobial effect ofendodontic antiseptics in vitro. Oral Surg Oral Med and Oral
Pathol 36: 856-871

UNEP PUBLICATIONS

377