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EC number: 202-704-5 | CAS number: 98-82-8
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
A summary of data on toxico-kinetics, metabolism and distribution is presented in Section 4.1.2.1 of the EU-RAR (2001, page 44ff).
Studies in animals
In vivo studies
The key study for this endpoint is identical to the one selected in EU RAR (see robust study summary in IUCLID Section 7.1.1). However, the study is presented in IUCLID data set under name CMA (Chemical Manufactures Association), while EU RAR cited the name of the performing laboratory.
The metabolism, disposition and pharmacokinetics of cumene has been investigated in detail in F-344 rats. Oral, iv and inhalation exposure were investigated. Investigation on each exposure route has been presented in one robust study summary. For human risk assessment exposure via inhalation route is considered to be the most relevant route.
After inhalation exposure cumene is absorbed rapidly and to about 100%. Concentrations in blood reached maximal levels at the end of a 6h exposure. After 6h exposure was terminated and excretion was investigated. After 24h the majority of cumene was excreted (~80%) and was excreted nearly completely after 72h (~95%). The predominant route of excretion was found to be urine with about 75 to 95 %.
Cumene is subject to metabolism. The major metabolite found in urine was 2-phenyl-2-propanol and its glucuronide and/or sulphate conjugates.
Other urinary metabolites are 2-phenylpropane-1,2-diol and 2-phenylpropionic acid. Very similar toxicokinetics are observed when single and repeated oral dose animal studies are compared.
There are some other studies presented in the EU RAR, which support the findings in the key studies, but are not presented here in detail. Percutaneous penetration of cumene has been described to occur at a rate similar to that obtained for benzene, toluene and p-xylene. Metabolism in rats (administered by gavage) revealed that 40% of the dose were metabolized to 2-phenylpropan-2-ol and 25% each to 2-phenylpropan-1-ol and alpha-phenylpropionic acid. Excretion of a single dose in rats were investigated but reported only as mmol SH/mol creatinine.
In vitro studies showed that rabbit liver soluble enzyme fraction metabolises cumene to 2-phenylpropan-1-ol, 2-phenylpropan-2-ol and 2-phenylpropionic acid. Cumene is able to inhibit Cytochrome P-450 dependent monooxygenases. Mean rates of in vitro metabolism of cumene have been reported to be in the range of 10 to 20 μg/min in rat liver and lung.
For investigations in humans the study of Senczuk and Litewka (1976) has been presented in detail. Absorption of cumene and the excretion of dimethylphenylcarbinol (2-phenylpropan-2-ol) has been investigated in human volunteers after head-only exposure. Retention of cumene in lungs during exposure decreased from 64% at 0.5 h of exposure to 45% at the end of each exposure. Maximum excretion of dimethylphenylcarbinol was observed after 6-8 h of exposure, diminishing after cessation of exposure approaching zero after 48 h. The average percentage yield of the conversion of cumene into 2-phenylpropan-2-ol was 35%.
Other studies in human reported that cumene has been reported to be associated with human metabolism and found as an organic constituent present in expired air of non-smoking normal healthy urban (man and women) population at low ng/L-level.
Cumene was also detected in the alveolar air, blood and urine of Italian blood donors, hospital employees and chemical workers from a benzene manufacturing plant.
For further information on these studies it is referred to the EU RAR.
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