Cumene Documentation of proposed values of occupational exposure limits (OELs)

Abstract

Cumene is a clear, colourless liquid with a strong aromatic gasoline-like odour. Cumene is used for the synthesis of phenol and acetone and as a solvent in paints, varnishes and res-ins. It is also used in the printing and rubber industries. According to data from Polish Chief Sanitary Inspectorate, in 2010, no workers were occupa-tionally exposed to cumene in concentrations exceeding Polish OEL values (100 mg/m3). In 2014, 51 workers were exposed to cumene in concentrations from 0.1 to 0.5 MAC value (from 10 mg/m3 to 50 mg/m3). Cumene vapours are irritating to the respira-tory tract. In humans, high concentrations of cumene cause painful irritation to the eyes and the respiratory tract. In animals, cumene caus-es mainly CNS depression. Chronic exposure to cumene can cause hepatotoxicity. In vitro tests indicated no mutagenic and no genotoxic potential of cumene. Intraperitoneal injection of cumene induced micronuclei in bone marrow of rats. Dose-related increases in DNA damage were observed in liver cells of male rat and lung cells of female mouse. A metabolite of cumene, α-methylstyrene, was not mutagenic in bacterial tests but induced chromosomal damage in cell cultures and ro-dent cells. IARC experts classified cumene in group 2.B – chemicals possibly carcinogenic to humans based on sufficient evidence in experimental animals for the carcinogenicity of cumene. Exposure of mice to cumene by inhalation in-creased the incidence of alveolar/bronchiolar adenoma and carcinoma in males and females mice, haemangiosarcoma of the spleen in male mice and hepatocellular adenoma in female mice. Exposure of rats to cumene by inhalation increased the incidence of nasal adenoma in males and females and renal tubule adenoma and carcinoma in male rats. Cumene is well absorbed. It is a lipophilic substance which is well distributed in the whole body. Cytochrome P-450 is involved in cumene me-tabolism. Main metabolite identified in urine was 2-phenyl-2-propanol and in exhaled air α-methylstyrene. In 2014, Scientific Committee for Occupational Exposure Limits to Chemical Agents (SCOEL) prepared change of indicative OEL for cumene – reduction of concentration from 100 mg/m3 (directive 2000/39/WE) to 50 mg/m³, STEL value 250 mg/m3 remain unchanged. The compound was included in SCOEL carcino-genicity group D (not genotoxic and not affect-ing DNA chemicals), for which a health-based OEL may be derived on the basis of NOAEL value. Poland did not submit any comments on SCOEL proposal during public consultations in 2014. A new indicative OEL was derived on the basis of 3-month NTP inhalation studies in rats and mice. SCOEL established 310 mg/m³ (62.5 ppm) level as a NOAEC for hepatotoxici-ty. A STEL of 250 mg/m3 (50 ppm) have been recommended to protect against respiratory tract irritation and behavioural effects. More-over, a “skin notation” was recommended because of its probable skin penetration. BLV recom-mended by SCOEL is 7 mg 2-phenyl-2-propanol per gramme of creatinine in urine (after hydrolysis). To determine MAC value for cumene hepato-toxicity and nephrotoxicity were adopted as a critical effect. The Expert Group for Chemi-cals Agents established 310 mg/m³ as NOAEC based on 3-month NTP inhalation studies in rats and proposed reduction of the current MAC value from 100 to 50 mg/m3. It was agreed that the previous STEL value of 250 mg/m3 should remain unchanged, which is also in accordance with the value recom-mended by SCOEL. Recommended BEI value is 7 mg 2-phenyl-2-propanol per gramme of creatinine in urine (after hydrolysis), sampled immediately after work shift. It was recom-mended to remain “I” (irritant) and “Sk” (sub-stance can penetrate skin) labelling of cumene.