p-cresol

Endpoint summary

Additional information

Fish:

Valid tests on acute toxicity to fish are available for 9 freshwater and 1 marine species.

The acute toxicity of p-cresol to fish was determined with a static bioassay on several freshwater species. The highest toxicity is a 96h LC50 value of 4.4 mg/L with Salmo trutta.

The chronic toxicity of p-cresol to fish was tested with Pimephales promelas in an Early-Life Stage Toxicity Test equivalent to OECD Guideline 210. The 32d NOEC is 1.35 mg/L.

Invertebrates:

The short term toxicity of p-cresol to freshwater invertebrates (Daphnia magna) was measured according to German Guideline DIN 38412 part 11. The EC50 (48 h) is 7.7 mg/L. The toxicity of p-cresol to the freshly fertilized eggs of the marine sea urchin Strongylocentrotus droebachiensis was determined by a static test. For p-cresol the EC50 (96 h) is 5 mg/L.

The long-term toxicity of p-cresol to aquatic invertebrates was determined in a semi-static test according to the preliminary guideline proposal of the German Umweltbundesamt from1984. After 21 days of exposure a NOEC of 1 mg/l was determined.

Toxicity to aquatic algae and cyanobacteria:

The toxicity of p-cresol to the green algae Desmodesmus subspicatus (former name Scenedesmus subspicatus) was determined according to DIN 38412 part 9 (draft standard for cell multiplication inhibition). Based on nominal concentrations a 48 h-EC50 of 21 mg/l and an EC10 of 4.6 mg/l (both related to growth rate) were determined.

Microbiological Activity in Sewage Treatment Systems:

The sensitivity of activated sludge to p-cresol was determined by a respiration inhibition test according to OECD Guideline 209. The 2h IC50 for respiration inhibion of microorganisms is 440 mg/L. The effect of p-cresol on Nitrosomonas activity was measured as a nitrification inhibition method comparable to ISO/DIS 9509. The 24 h-IC50 was 27 mg/L. For respiration, the 49 h-IC50 was 260 mg/L. Nitrification inhibition by p-cresol was also measured by a similar method yielding an EC75 of 16.5 mg/L during a 2 -4 h incubation period. The EC50(48 h) with respect to growth of Tetrahymena pyriformis accounts for 157 mg/L testing p-cresol.

Suspected Endocrine Properties of p-cresol:

The below mentioned data are not given as robust study summaries as IUCLID does not supply relevant endpoint summaries. A literature survey for endocrine properties of cresols in aquatic organisms was performed in 2014. Relevant hits were chosen and assessed as follows:

Source	Assessment
Barron MG, Adelman IR (1984):Nucleic acid, protein content, and growth of larval fish sublethally exposed to various toxicants. Canad. J. Fish. Aquat. Sci. 41(1), 141-150.	FELS.test (chronic fish test, key-study in p-cresol dossier.)Conclusion: No hint on endocrine properties.
Nishihara T, Nishikawa J, Kanayama T, Dakeyama F, Saito K, Imagawa M, Takatori S, Kitagawa Y, Hori S, Utsumi H (2000):J. Health Science 46, 282-298	In vitro study (yeast two-hybrid assay) with some similarities to YES/YAS-test. The authors tested a ED effects for over 500 chemicals. The effect at a concentration showing 10% activity of 10−7 Mole/L 17ß-estradiol was chosen arbitrary as “ED posititve”. 17ß-Estradiol showed an effect at 3E-10 Mole/L, o-cresol showed no effects at 1.0E-05 Mole/L. For p-cresol an effect at 3.0E-04 Mole/L was reported. The author`s procedure why a lot of substances were only analysed at very low concentrations (and in many cases not marked as ED) and other substances were analysed in higher concentrations (and marked as ED) is unclear. From all substances marked as “positive”, p-cresol belongs to the group where effects were reported only in higher concentrations. Conclusion: p-Cresol was tested as ED positive, o-cresol as negative. Interpretation of results as ED positive is arbitrary and not commonly accepted. The effect reported was obtained at a rather high concentration of 3.0E-04 Mole/L which is equivalent to 32.4 mg/L. This number is in the order of magnitude or even higher as the typical acute toxic effects in aquatic organisms (e.g.: fish LC50 fish = 4.4 mg/L, algae EC50 = 21 mg/L). This leads to the conclusion that, the effect measured for p-cresol effect is not a low-dose effect but caused by high-dose toxic effects on the test system. Overall, this study is assessed as not reliable for suspecting p-cresol as ED.
Environment Agency, UK, (2007):Endocrine disruption horizon scanning: priority and new endocrine disrupting chemicals, Science Report – SC030276/SR3,https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/291652/scho0507bmqc-e-e.pdf	Literature survey performed by UK EA with focus on screening for endocrine disrupters. Contained is a list of 146 substances with potential ED potential. The list does contain 66 substances with proved ED potential.Conclusion:: p-Cresol is not listed as suspected ED.
USEPA, 2012, Endocrine Disruptor Screening Program; Universe of Chemicals	List of several thousand substance for potential ED-Screening.Conclusion: m-Cresol, o-cresol and p-cresol are found in the list
USEPA, 2013, Endocrine Disruptor Screening Program; Final Second List of Chemicals and Substances for Tier 1 Screening http://www.epa.gov/scipoly/oscpendo/	Two lists with 25 and 109 potential ED-substances. Obviously is this list a cleaned version of the EPA list of 2012. Conclusion:  p-Cresol is not listed as suspected ED.
Varadarajan R, Sankar H, Jose J, Philp B (2014):Sublethal effects of phenolic compounds on biochemical, histological and ionoregulatory parameters in a tropical teleost fish Oreochromis mossambicus, Int. J. Scient. Res Pub, 4, 1-12	In-vivo-study: Estrogenic activity was not analysed. The authors discuss whether low levels of Cortisol in blood might be a hint that m-cresol could influence the steroid biosynthesis. Conclusion: The study does not give information on mode of action or adverse effects.Oreochromis mossambicus is not a standard organism.Endpoints: Level of Cortisol om blood, Glucose 6-phosphatase, estimation of Branchial ATPases, analysis of gillsConclusion::The study does not give relevant information on ED properties of p-cresol

Summary on suspected endocrine properties: Only one experimental study was published (Nishihara 2000) which described an assay for testing ED properties where cresols were tested. p-Cresol was marked as ED postitive, whereas o-cresol was negative. The criteria for defining positive or negative however are arbitrary and not commonly accepted and the selection of concentrations tested is unclear. The effects concentrations reported are in very high regions where intoxication of the test system is expected . In an EPA list from 2012, for p-cresol was mentioned as suspected endocrine disruptor, but removed in 2013. A list from UK EA did not contain p-cresol as suspected ED. Currently there are no grounds for suspecting p-cresol as having endocrine properties in aquatic organisms.