A controlled study was made of the effects of natural orange juice, synthetic orange juice, and placebo in the prevention of the common cold; both natural and synthetic orange juices contained 80 mg of ascorbic acid daily. Three-hundred sixty-two healthy normal young adult volunteers, ages 17 to 25 years, were studied for 72 days with 97% of participants completing the trial. There was a 14 to 21% reduction in total symptoms due to the common cold in the supplemented groups that was statistically significant (P less than 0.05). Ascorbic acid supplementation also increased the number of "episode-free" subjects. However, the clinical usefulness of the results does not support prophylactic ascorbic acid supplements in the well-nourished adult. The results in this study with both natural and synthetic orange juice of physiological content of ascorbic acid, are similar to those obtained using a "megadose" of ascorbic acid.

The in vitro rates of aging and spontaneous reactivation of human plasma cholinesterase (ChE) after inhibition by several organophosphorus pesticides (OPs) have been studied. After inhibition by OP the enzyme can undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the enzyme. The rates of these two reactions depend on the nature of the phosphoryl group of the OP bound to the active site of ChE. Most OPs registered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom. Reaction rate constants for aging and spontaneous reactivation are reported. Dimethoxy OPs cause half-lives of aging in human plasma ChE of approximately 6 hours and 23 hours at 37°C and 22°C respectively; for diethoxy OPs the values are 12 hours and 39 hours. Reappearance of enzyme activity, after removal of OP, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours and 15 hours at 37°C and 22°C. These effects, both in vivo and ex vivo, may have relevance in developing a monitoring strategy for dimethoxy OPs using plasma ChE measurements. Inhibition by diethoxy OPs spontaneously reactivates very slowly, even at 37°C, and would not practically influence the measured inhibition. No spontaneous reactivation was detected in human plasma ChE inhibited by the methoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylamino substituted OP (crufomate) during 45 hours incubation at 37°C.

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ABsTRAcr The effect of a dose of alcohol on the kinetics of mandelic acid excretion in four volunteers exposed to 220 mg/m3 styrene has been investigated under controlled exposure chamber conditions. Ethanol inhibited the excretion of mandelic acid, so that the peak excretion was delayed from the end of the exposure period until three hours afterwards. One hour after administration of ethanol blood mandelic acid concentrations were 56% of the levels found during the alcohol-free control exposure, and this was paralleled by a 15-fold rise in phenylethane 1,2 diol, the metabolic precursor of mandelic acid. It is suggested that the inhibition of the oxidation of this diol is related to the change in NAD+/NADH ratio produced by ethanol metabolism. The implications of this ethanol effect on the interpretation of urinary mandelic acid excretion when monitoring workers exposed to styrene are discussed.It is now established that monitoring workers exposed to styrene vapour is best accomplished by measuring the excretion of mandelic acid in the urine.1-5 The usefulness of mandelic acid determinations depends on the time of taking the urine sample after the end of the workshift.6 Several authors have suggested end-of-shift sampling while others have recommended next-morning samples."--In an earlier study we reported a detailed investigation of the daily excretion of mandelic acid by two technicians building glass-reinforced plastic boats under model ventilation conditions.7 Both these subjects showed maximum mandelic excretion several hours (4-8 hours) after the end of exposure. The time-lag was relatively constant for each individual and not related to level of exposure. We suggested that such a time lag in maximum excretion rates required a modification of sampling strategy. Our report of this time-lag in excretion has caused some controversy. Guillemin and Bauer"2 reviewed those papers reporting a time-lag and have contrasted these reports with their experience that experiments with volunteers under controlled exposure-chamber conditions show that maximum excretion occurs at or near the end of exposure. Since their publication we have confirmed that under controlled exposure chamber conditions maximum excretion of mandelic Received 15 March 1982 Acccepted 7 May 1982 acid does occur at the end of the exposure period. On the other hand, we have also found that a significant proportion of industrial workers in the glass-reinforced plastic boat industry that we have studied in detail show a delayed excretion of mandelic acid. This difference in excretion kinetics between volunteers under controlled conditions, and workers building glass-reinforced plastic boats requires explanation. Among the factors considered was the effect of the ingestion of alcohol. Alcohol affects the metabolism of xylene, toluene, and trichloroethylene."3-16 In this study we have investigated the effect of alcohol ingestion on the excretion of mandelic acid by volunteers under controlled exposure conditions.

Breath analysis is an attractive noninvasive procedure for screening workers exposed to solvents. It has been used in numerous laboratory based studies and for field research. Despite the obvious advantages in routine biological monitoring it has failed to become widely accepted as a tool in occupational hygiene. Recent advances in breath sampling and analysis are such that it is likely to become more widely used in the future. In this paper, the past 5 years have been reviewed to try to assess what developments might now contribute to the increased use of breath analysis in biological monitoring; in particular, the development of a selected ion flow tube mass spectrometer for real time direct analysis of trace gases in breath and the more immediately available and less expensive indirect methods involving collection devices with adsorbent tubes is important. The introduction of guidance values for biological monitoring with clear advice on sampling times and the recognition of the importance of quality assurance programmes will help improve confidence in the technique. (Occup Environ Med 1999;56:753-757)

A new specific and sensitive method has been used to monitor workers from five different factories where 4,4'-diaminodiphenylmethane (methylene dianiline) (DDM) was being used. The isolation and identification of an N-acetyl conjugate of DDM, a major metabolite of DDM found in human urine, is reported for the first time. The use of this biological monitoring method will allow the assessment of the absorption of DDM and help in monitoring improvements in work practices, particularly where exposure may occur through pathways other than inhalation.4,4' Diaminodiphenylmethane (DDM) is a commercially important aromatic amine used in the production of isocyanates, polyisocyanates, polyurethane foams, and elastomers and as an epoxy resin hardener.' It is commonly referred to as methylene dianiline (MDA) (CAS 101-77-9). Several workers have studied the toxicity of DDM. It has been reported to be hepatoxic in rats,2 3 dogs,4 and man.5 It is mutagenic in the Ames test in the presence, but not in the absence, of an S9 metabolising system9 and has been reported to be carcinogenic in rats and mice.'0 " I As a result of these findings and the close chemical similarity of DDM to other aromatic amines, which are proved or suspect human carcinogens, DDM is under scrutiny by regulatory bodies in the United States.Occupational exposure to DDM may be assessed by measuring DDM concentrations in the work environment and by biological monitoring. DDM, like 3,3'-dichloro 4,4'-diaminodiphenylmethane (commonly known as 4,4' methylene bis 2-chloroaniline or MBOCA) and other aromatic amines, has the potential for considerable skin absorption. Analysis of urine samples from workers exposed to MBOCA is helpful in assessing absorption and in monitoring improvements in occupational hygiene.'2 Analytical methods have been reported for the analysis of DDM in workplace air using high performance liquid chromatography (HPLC) with ultraviolet detection'3 and in blood using gas chromatography (GC) with elecAccepted 3 March 1986. tron capture detection.'4 The work reported here describes the use of a new sensitive and specific gas chromatographic-mass spectrometric (GCMS) method for measuring DDM in urine. This approach was adopted after we had used HPLC and GC methods and had noted that occasionally interfering peaks were present in urine. We also describe for the first time the isolation and identification of N-acetyl DDM, a major metabolite of DDM found in human urine. These findings are used to devise a biological monitoring method for monitoring workers exposed to DDM. Materials and methods URINE SAMPLESUrine samples were collected from 111 workers at five factories using DDM. Factories A and B were packaging DDM as a component of a hardener in a two part epoxy resin formulation, factories C and D were using DDM and other compounds to impregnate carbon fibre mats, and factory E used DDM as a component in a screen printing process for seals and gaskets. Urine samples were collected in polycarbonate bottles towards the end of a working sh...

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1. The steps involved in determining the chirality of the mandelic acid excreted by rats after administration of ethylbenzene and styrene were investigated by studying the fate of racemic, (R)- and (s)1,2-phenylethanediol, a precursor of mandelic acid. These investigations indicate the occurrence of two alternative routes of metabolism for 1,2-phenylethanediol, one involving retention of configuration and the other resulting in the loss of the chiral centre. 2. The stereoselectivity of the disposition of mandelic acid was investigated; rats were dosed with mandelic acid either as the racemate or as the individual enantiomers, G.1.c.-mass spectrometry and h.p.l.c. were used to determine the enantiomers of mandelic acid. 3. There were at least two routes by which mandelic acid could be metabolized and/or excreted; there is a stereoselective pathway in rat for (s)-mandelic acid, which gives rise to phenylglyoxylic acid. 4. The chiral inversion of (s)-mandelic acid to (R)-mandelic acid is reported; although this has been observed in bacteria it has not previously been observed in mammals. 5. The extent to which mandelic acid is metabolized to phenylglyoxylic acid is dependent on the enantiomeric composition of the mandelic acid administered. There is no evidence to indicate significant ketone-alcohol conversion, that is phenylglyoxylic acid is not significantly reduced to mandelic acid in vivo.