IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

(b) Distribution
STYRENE 485
An early study in which [ 14 C]styrene labelled at the β-carbon atom was administered
subcutaneously to Wistar rats (0.10 mL of a 20% solution to 100–125-g rats [20 mg per
animal]) indicated that styrene was distributed rapidly (< 1 h) to tissues and that
excretion of the radioactivity was primarily via the urine, with only a small fraction
(2–3%) exhaled unchanged by the lung and approximately 12% appearing as 14 CO 2
during 24 h after dosing (Danishefsky & Willhite, 1954).
Teramoto and Horiguchi (1979) exposed rats [strain unspecified] to 500 and
1000 ppm [2130 and 4260 mg/m 3 ] styrene by inhalation for 4 h and found the highest
concentration of styrene in adipose tissue. The biological half-life in this tissue was
6.3 h, as opposed to 2.0–2.4 h in blood, liver, kidney, spleen, muscle and brain. No accumulation
of styrene was found when rats were exposed to 700 ppm [2980 mg/m 3 ] for 4 h
per day for five days. Withey and Collins (1979) exposed Wistar rats to styrene by inhalation
(50–2000 ppm [213–8520 mg/m 3 ] for 5 h) and found a proportionally increasing
level of styrene uptake into blood. Tissue distribution was concentration-dependent, and
the concentration of styrene in the perirenal fat was higher than in any other tissue. This
is probably a consequence of the high oil:blood partition coefficient of styrene (130; see
Van Rees, 1974). When [ 14 C]styrene was administered orally to rats (20 mg/kg), the
highest levels of radioactivity were found in the kidney followed by the liver and
pancreas. Ninety per cent of the dose appeared in the urine within 24 h after dosing
(Plotnick & Weigel, 1979). Löf et al. (1983, 1984) studied the effect of time and dose on
styrene distribution and metabolism following intraperitoneal administration of styrene
(1.1–4.9 mmol/kg bw) to NMRI mice. The highest concentrations of styrene were
measured in adipose tissue, pancreas, liver and brain. Styrene 7,8-oxide concentrations
were highest in kidney and subcutaneous adipose tissue and lowest in lung. The highest
concentrations of styrene glycol were found in kidney, liver, blood and lungs. Male
Wistar rats given styrene (100 mg/kg) by intubation excreted both R- and S-mandelic
acids, with a preference towards excretion of the R-form (Drummond et al., 1989).
The uptake of styrene by the upper respiratory tract of the CD-1 mouse and Sprague-
Dawley rat has been determined using a surgically isolated upper respiratory tract preparation
(Morris, 2000). In rats, steady-state uptake efficiency of styrene decreased with
increasing exposure concentration, with 24% and 10% efficiency at 5 and 200 ppm [21
and 852 mg/m 3 ], respectively. In mice, the uptake efficiency — which did not maintain
a steady state but declined during exposure — averaged between 42% and 10% at
5–200 ppm. Treatment with metyrapone, an inhibitor of cytochrome P450, abolished the
concentration-dependence of the uptake efficiency in both species, providing evidence
that inhaled styrene is metabolized by nasal tissues and that this determines the concentration-dependence.