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Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans have been exposed to azodicarbonamide (ADA) by inhalation where bulk quantities of ADA are handled in the workplace. Responses of some workers have led to concern for the potential irritant and sensitizing properties of inhaled ADA. This study examined the effects of inhaling ADA on lung structure and function of guinea pigs during and after an acute exposure. Groups of 20 guinea pigs were exposed to each of 3 concentrations of ADA (19, 58, and 97 mg/m3), plus air as a control, for 1 hr. Pulmonary function was measured before exposure (baseline), during exposure, immediately after exposure and 24 hr after exposure. Dynamic compliance (Cdyn), total pulmonary resistance (RL), tidal volume (VT), respiratory frequency and minute volume were measured. In addition, gross necropsies and histological examinations of respiratory tract tissues were done either immediately following the exposure or 24 hr after exposure. There were no effects of ADA exposure on gross necropsy, histology, Cdyn, or RL. Some significant, concentration-related decreases in VT, respiratory frequency and minute volume were seen. The magnitudes of these changes were small: the largest change was seen in minute volume, amounting to a 24% decrease in the high concentration group. Inhalation exposure of guinea pigs to ADA at concentrations of up to 97 mg/m3 resulted in minor changes in pulmonary function without any changes in lung histology.

1,3-Butadiene is produced commercially for use in the manufacture of elastomers, polymers and other chemicals. Recent inhalation carcinogenicity studies of butadiene indicate that B6C3F1 mice are more sensitive to the tumorigenic effects of inhaled butadiene than are Sprague Dawley rats. The purpose of this investigation was to determine if there were differences in distribution in tissues of inhaled butadiene between rats and mice. Male Sprague Dawley rats and B6C3F1 mice were exposed nose-only for 3.4 hr to (mean +/- SE) 1220 +/- 71 micrograms 14C-butadiene/L air and 121 +/- 2 micrograms 14C-butadiene/L air, respectively. Radioactivity was distributed widely in tissues immediately following exposure of both rats and mice to 14C-butadiene. In both species, respiratory tract tissue (lung, trachea, nasal turbinates), gastrointestinal tract (small and large intestine), liver, kidneys, urinary bladder and pancreas contained high concentrations of radioactivity within 1 hr after the end of exposure. In all cases, tissues of mice contained 15 to 100 times the concentration of 14C-butadiene equivalents per mumole of butadiene inhaled than did rats. For both rats and mice, elimination of 14C from tissues and blood was rapid, with 77% to 99% of the initial tissue burden being eliminated with half-times of 2 to 10 hr. Within 1 hr after the end of exposure, all rat tissues retained a substantial amount of 14C that was associated with volatile material (20% to 40% of the total 14C in tissues) that was probably butadiene and/or metabolites. A similar observation was noted in mouse liver, the only tissue of mice examined.(ABSTRACT TRUNCATED AT 250 WORDS)