Fd Chem. Toxic. Vol. 26, No. 8, pp. 715-716, 1988 0278-6915/88 $3.00+0.00 Printed in Great Britain. All rights reserved Copyright © 1988 Pergamon Press plc BRIEF COMMUNICATION FORMALDEHYDE CONCENTRATIONS IN THE BLOOD OF RHESUS MONKEYS AFTER INHALATION EXPOSURE M. CASANOVA, H. D'A. HECK*, J. I. EVERITT, W. W. HARRINGTON, JR and J. A. PoPP Chemical Industry Institute of Toxicology, PO Box 12137, Research Triangle Park, NC 27709, USA (Received 29 April 1988; revisions received 6 May 1988) Abstract--The effect of subchronic exposure to formaldehyde (HCHO; 6 ppm; 6 hr/day, 5 days/wk for 4 wk) on the HCHO concentration in the blood of three rhesus monkeys was investigated. Immediately after the final exposure, the monkeys were sedated, and blood samples were withdrawn 7 min after the end of exposure. The HCHO concentration in the blood, determined by gas chromatography-mass spectrometry was 1.84 + 0.15 #g/g blood and did not differ significantly after a further 45 hr without exposure to HCHO (2.04+ 0.40#g/g blood). The average concentration of HCHO in the blood of exposed monkeys was also not significantly different from that of three unexposed controls (2.42 + 0.09#g/g blood). However, individual monkeys differed significantly from one another with respect to their blood concentrations of HCHO. These results indicate that subchronic inhalation exposure of non-human primates to HCHO has no significanteffect on the HCHO concentration in the blood, and that the average concentration of HCHO in the blood of monkeys is similar to that in the blood of humans. INTRODUCTION There was no evidence of an effect of formaldehyde (HCHO) exposure on the HCHO concentration of the blood in rats exposed to 14.4ppm (2hr) and in humans exposed to 1.9 ppm (40 min) of HCHO (single exposures; Heck et al. 1985). Nonhuman primates are presumably a more appropriate animal model than rats for studying the effects of HCHO exposure on man, and exposure of nonhuman pri- mates to HCHO for longer periods may provide information relevant to the possible effects of sub- chronic exposure of humans to HCHO. This paper summarizes the results of determining the HCHO concentrations in the blood of monkeys after a subchronic exposure to a moderately high concen- tration of HCHO (6 ppm; 6 hr/day, 5 days/wk, for 4 wk) and in that of three unexposed monkeys. At this concentration of HCHO, a low incidence of nasal squamous cell carcinomas occurred in rats in a 2-yr bioassay (Kerns et al. 1983). MATERIALS AND METHODS Monkeys. Six young adult rhesus monkeys (Macaca mulatta; Hazleton Primates, Alice, TX) aged 3-5 yr and weighing 6-7 kg were used. Animals were individually housed in stainless-steel cages with a 12-hr light/dark cycle. Food (Purina Certified Monkey Chow 5048) and water were provided ad lib. except during exposure. *To whom reprint requests should be addressed. Abbreviations: GC-MS = gas chromatography-mass spec- trometry; HCHO = formaldehyde; PFPH = penta- fluorophenylhydrazine. Exposure procedure. Exposures were conducted in 15 m 3 stainless-steel and glass inhalation chambers similar to those described by Hinners et al. (1968). Chamber airflow, temperature and relative humidity were maintained at approximately 4000 litres/min, 22°C and 52%, respectively. Formaldehyde gas was generated by the thermal depolymerization of para- formaldehyde contained in a stainless-steel canister enclosed in an isothermal oven. A 6 litres/min stream of air passing through the canister carried the HCHO gas to the chamber air supply for mixing before introduction into the chamber (Chang et al. 1981). Chamber concentrations were monitored con- tinuously with a Foxboro 1A infrared spectropho- tometer. Infrared analyses were verified at least weekly by the chromotropic acid method (NIOSH, 1984). The analytical chamber concentration was 6.00 _ 0.22 ppm. Collection of blood samples. Immediately after the exposure, the monkeys were sedated with 40 mg of ketamine hydrochloride (Parke-Davis, Morris Plains, N J). Approximately 3 ml of blood were withdrawn from the tarsal vein, and approximately 1 ml was added to each of three preweighed tubes containing a solution of H3PO4 and pentafluorophenylhydrazine (PFPH; PCR Research Chemicals, Gainesville, FL; see below). To examine whether ketamine affects the blood concentration of HCHO, blood samples were drawn in separate experiments from monkeys not treated with ketamine. There was no apparent effect of ketamine on the HCHO concentration of the blood. Analysis of HCHO in blood. The procedure used to determine the HCHO concentration in the blood of monkeys was essentially identical to that previously used for the analysis of HCHO in the blood of rats and human volunteers (Heck et al. 1985). Briefly, 715