Styrene Oxide in Blood, Hemoglobin Adducts, and Urinary Metabolites in Human Volunteers Exposed to 13C8-Styrene Vapors

4-Vinylphenol-Induced Pneumotoxicity and Hepatotoxicity in Mice

“…In recent studies we were unable to demonstrate the formation of 4-VP from styrene in rodent microsomal preparations but found that 4-VP was rapidly metabolized by mouse and rat hepatic and pulmonary microsomes involving CYP2E1 and CYP2F2 (7). In a recent study in which rats and mice were exposed by inhalation to [ring-U- 14 C]styrene, Boogaard et al (5) reported nding 14 CO 2 . They suggested that ring hydroxylation may be occurring followed by ring opening.…”

“…They suggested that ring hydroxylation may be occurring followed by ring opening. Recent studies in which human volunteers inhaled 13 C 8 -styrene were unable to nd products that could be derived from ring hydroxylation (14).…”

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of styrene

“…Mandelic acid was reported to represent 57-80% of a styrene dose and phenylglyoxylic acid, 10-33% (ATSDR, 1992;Rebert and Hall, 1994). In four male volunteers who inhaled 50 ppm styrene vapors for 2 hr, mandelic acid represented 6-29% of the retained dose, and phenylglyoxylic acid represented 4-6% of the dose (Johanson et al, 2000). [The Expert Panel noted that lower metabolite recoveries in the Johanson et al (2000) study likely reflected an unknown amount reaching blood.]…”

“…Half-lives for inhaled styrene were reported at 0.6 hr for the first elimination phase and 13 hr for the second elimination phase (ATSDR, 1992). The half-life for styrene oxide [assumed to be for the first elimination phase] was reported at 1.8 hr (Johanson et al, 2000). Half-lives for urinary elimination of mandelic acid were reported at 3-4 hr and 25-40 hr for each respective phase (ATSDR, 1992;Rebert and Hall, 1994).…”

“…In four male volunteers who inhaled 50 ppm styrene vapors for 2 hr, mandelic acid represented 6-29% of the retained dose, and phenylglyoxylic acid represented 4-6% of the dose (Johanson et al, 2000). [The Expert Panel noted that lower metabolite recoveries in the Johanson et al (2000) study likely reflected an unknown amount reaching blood.] IARC reported that in humans, metabolites generated through ring epoxidation of styrene (i.e., vinylphenol), conversion of styrene to 1-phenylethanol (i.e., ultimately leading to formation of hippuric acid), glutathione conjugation of styrene oxide, and glucuronidation of phenylethylene glycol represent o1% of the retained styrene dose.…”