m-Cresol - ipcs inchem

OECD SIDS
m- / p-CRESOL
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 of
cresol 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 pharmaceutical
injection 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 the
intact 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 the
benzene ring (all isomers) and, for p-cresol, side-chain oxidation to p-hydroxybenzoic acid (Bray et
al. 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 (Mandel
1971). 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 with
dose (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 a
reactive quinone methide intermediate was found in rat liver in vitro.
UNEP PUBLICATIONS 15