Unexposed Control Group Research Articles

Letter from the Editor

The purpose of this review has been to discuss human and environmental factors which may influence the acute irritative and neurotoxic effects of organic solvents. The review is based on a field study and on four human experimental studies. Several studies have shown that printers and other workers exposed to mixtures of solvents experience an increased frequency of work related irritative and neurological symptoms although the exposure has been far below the occupational exposure limits. A series of controlled human exposure studies was carried out. Different groups of persons were exposed to the most frequent solvent, toluene. Toluene in alveolar air and the urinary excretion of the metabolites were measured and the acute effects of toluene were assessed by the performance in a series of test of the perceptual and psychomotor functions as well as a standardized registration of annoyance and symptoms. The pharmacokinetics of toluene is complex and there is a large individual variation in the excretion of the metabolites. This variation can only to a limited extend be related to known variables. Intake of alcohol during exposure inhibits the metabolism of toluene and increases the internal dose. Normal therapeutic doses of cimetidine or propranolol have no measurable effect on toluene metabolism. Exposure to 100 ppm during 7 h causes irritation in the eyes and airways as well as feeling of intoxication, dizziness, and headache. There are signs of impairment in the performance in test concerning visual perception, colour vision, vigilance as well as the psychomotor functions. However, the influence on the performance tests was not seen in all studies. Variations in the air concentration of toluene with peaks op to 300 ppm causes fluctuation in the alveolar concentrations, but no acute effect of these peaks or of increased physical activity during exposure could be detected. However, the importance of peek concentrations and of workload for the development of chronic solvent encephalopathy is still unknown. The influence of a 9-25 years occupational exposure to solvents was investigated. A group of printers occupationally exposed to mixtures of solvents were compared with a matched unexposed control group. There was no difference between printers and controls in the performance in the psychological test, but in two of the tests there were tendencies to increased sensitivity to toluene in the group of printers. It is concluded that exposure to toluene corresponding to the occupational limit in several countries cause irritative and prenarcotic symptoms and possibly a lowered performance.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of ultraviolet radiation on wound healing

The effects of prior ultraviolet light exposure on wound tensile strength and skin histology were evaluated in the hairless guinea pig model. Hairless guinea pigs (strain IAF/HA-HO) were irradiated with either UVA (80 J/cm 2) or UVB (0.46 J/cm 2) every other day for 16 weeks. Following cessation of treatment, a standard dorsal wound was made in each animal, allowed to heal, and mechanically tested to failure at 21 days. Serial 4 mm punch biopsies were obtained prior to the initial exposure and at 2, 4, 8, 12 and 16 weeks. Histological examination with haematoxylin and eosin, trichrome and elastin stains was performed. In comparison to the unexposed control group, wound tensile strength was significantly less in teh UVA- and UVB-irradiated animals. Histological examination revealed a marked endothelial swelling and eosinophilic infiltration in the irradiated groups. These results indicate that repeated exposure to even moderate doses of non-ionising radiation alters normal skin structure and adversely affects subsequent wound tensile strength in this model.

Subclass distribution of IgG and IgA antibody response to Pseudomonas pseudoalcaligenes in humans exposed to infected metal-working fluid

The subclass distribution of the IgG and IgA antibody response in serum was studied in humans exposed to aerosolized metal-working fluid containing Pseudomonas pseudoalcaligenes. This species was consistently found in concentrations of 10(8) bacteria per milliliter of metal-working fluid during 1 year of observation. No increased frequency of respiratory infections or discomfort was related to the exposure to the infected fluid. The antibody response to the bacterium consisted predominantly of IgG1 and IgG2 antibodies. IgG2 antibodies dominated the antibody response to the lipopolysaccharide of the bacterium. IgA1 and IgA2 antibodies were also found. Smokers had significantly reduced antibody levels of all subclasses compared with nonsmokers. The antibody levels in smokers did not differ from levels of the unexposed control group. Analyses of the total serum immunoglobulin concentrations with respect to subclasses revealed that the total IgG2 levels were also significantly reduced in smokers. In nonsmokers, the age of the individuals influenced the antibody levels of the IgG1, IgG2, IgA1, and IgA2 subclasses, the levels decreasing with increasing age. For smokers, the correlation between age and antibody levels was only obvious for IgG2 antibodies. Decreased IgG2 antibody levels in the smokers were also accompanied by decreased FEV1 values (p less than 0.01). Subclass analysis of the antibody response to P. pseudoalcaligenes demonstrated that the subclass pattern for the whole bacterium differed from the pattern of the major cell wall component, the lipopolysaccharide. The significance of qualitative and quantitative differences in the subclass antibody response is discussed.

Embryonic catch-up growth after exposure to the ketone body D,L,-beta-hydroxybutyrate in vitro.

The capability of rodent embryos to recover in growth and development subsequent to exposure to an insult was investigated employing whole embryo culture. Early somite stage mouse embryos were exposed to 32 mM D,L,-beta-hydroxybutyrate (D,L,-beta OHB) for 24 hr (Period I), and were then transferred and maintained in control medium for an additional 36 hr maximum (Period II). Growth of this recovery group (Group B) was monitored at various time points of Period II and the results were compared with an unexposed control group (Group A) and another continuously-exposed reference group (Group C). At the end of Period I, 100% of D,L,-beta OHB-exposed embryos exhibited neural tube closure defects and were growth retarded. At 36 hr of Period II, cranial and caudal neural tube defects of Group B embryos were reduced to 3-7% and 0%, respectively. These embryos also demonstrated an excess in growth velocity during recovery so that at the end of Period II, total protein content was comparable to control values. In contrast, Group C embryos remained growth retarded and showed a significant increase in cranial and caudal neural tube defects (20 and 75%, respectively). Thus, neurulating mouse embryos were capable of catch-up growth following an embryotoxic exposure to D,L,-beta OHB. The progression of development of total protein values and morphological features such as elimination of neural tube defects was intimately related to the amount of time allowed for recovery. Moreover, an elevation of growth rate over normality, which is characteristic of catch-up growth, was observed.

Visceral pleural thickening in asbestos exposure: the occurrence and implications of thickened interlobar fissures.

We evaluated fissural (ie, visceral pleural) thickening on radiographs in two asbestos-exposed study populations and a control group. Asbestos workers had an incidence of fissural thickening of 54.5% compared with 16.0% in the unexposed control group, with a strong positive statistical effect due to asbestos exposure beyond that attributable to age. Fissural thickening occurred in 85% of workers with parietal plaques and in 36% without pleural plaques. Fissural thickening occurred in 45% without radiographic evidence of pulmonary fibrosis, but it was very common (85%) in those with pulmonary fibrosis. Data analysis showed that fissural thickening responds more strongly to asbestos exposure than does plaque formation, with 21 years of asbestos exposure needed for a 50% chance of developing fissural thickening, while 31 years of exposure were needed for a 50% chance of forming pleural plaques. From a second group of 57 asbestos workers evaluated clinically, 8 were diagnosed as having asbestosis with radiographically clear lungs and fissural thickening. We conclude that visceral pleural thickening is common in asbestos exposure, that it is related to the years since first asbestos exposure, and that its presence may indicate the presence of pulmonary asbestosis, even with radiographically normal lungs.

Stereometabolism of styrene in man. Urinary excretion of chiral styrene metabolites.

Chiral styrene metabolites obtained during initial styrene exposure of test persons were determined in urine samples using capillary gas chromatography. A typical time-dependent urinary concentration profile of one person over a 49-h period is presented and compared with the results of a previous study of occupationally exposed workers and an unexposed control group. Maximum levels of excretion of all styrene metabolites were observed at about the end of a 9-h workshift. Forty hours after exposure, the L/D-ratio of mandelic acid had subsided to the initial value, and the L/D-ratio of phenylethylene glycol to a value equal or slightly above the initial value.

Chromosome aberrations in individuals occupationally exposed to ethylene oxide, and in a large control population

Chromosome aberration frequencies in 61 employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. We studied 3 worksites with differing historical ambient levels of ETO. Within worksites, groups were classified as high potential exposed, low potential exposed, or controls. Further control groups including an off-site community control group were added to give a total of 304 control individuals. Blood samples were drawn several times over a 24-month period. Aberrations were analyzed in 100 cells per sample after culture for 48–51 h. Worksites I, II and III respectively represented increasing levels of potential ETO exposure. At worksites I and II, no consistent differences in aberration frequencies were found among groups. At worksite III aberration frequencies in potentially exposed individuals were significantly increased compared with controls. The frequencies of cells with aberrations were 5.6% for the 2 individuals in the high potential exposure category and 2.6% for 23 persons in the low potential exposure group. The overall frequency of cells with aberrations in the matched control individuals was 1.4%. In the total control group of 304 individuals we found significant increases in aberrations associated with smoking and with increasing age. We have also reported previously an association between sister-chromatid exchange (SCE) frequency and ETO exposure (Stolley et al., 1984). When aberration frequencies were compared with levels of SCEs there was only a weak overall association. The correlation was found in potentially exposed but not in control groups, and for any individual, one observation could not be used to predict the other.

A health examination of railway high-voltage substation workers exposed to ELF electromagnetic fields.

This is a cross-sectional survey on the health conditions of railways workers active in 258 interconnection and conversion substations all over Italy. Measurements performed in both kinds of substations operating at 220 kV have shown that maximum levels of the electric field strength and of the magnetic flux density at 50 Hz are of the order of 5 kV/m and 15 microT, respectively. Three subject groups, differently exposed (1, 10, 20 h/week), and an unexposed control group, for a total number of 627 workers, constitute the population at study. All subjects underwent a general medical examination, laboratory investigations, and a series of selected examinations relative to three systems (nervous, cardiovascular, and haematopoietic) considered at higher risk. No differences have been found between the exposed and the control groups. It is concluded that workers exposed to ELF electromagnetic fields of moderate strength do not show the presence of clear effects on their state of health.

Frequency, sensitivity and specificity of roentgenographic features of slight and moderate asbestos-related respiratory diseases.

The possibility of early detection of asbestos-related respiratory diseases was examined on the basis of four x-ray abnormalities, namely, pulmonary fibrosis, pleural plaque, diffuse pleural thickening and diaphragmatic calcification, in a group of workers exposed to chrysotile asbestos. The frequency of these phenomena was compared to the unexposed control group of similar distribution of number, sex and age. Besides the pleural plaques, which had a high specificity, the combination of minor x-ray abnormalities proved to be most characteristic of exposure to asbestos. The more frequent one of the abnormalities, the less specificity it had to asbestos exposure.

Stereometabolism of styrene in man: gas chromatographic determination of phenylethyleneglycol enantiomers and phenylethanol isomers in the urine of occupationally-exposed persons

A gas chromatographic procedure for the determination of phenylethyleneglycol enantiomers and phenylethanol isomers is described and applied to the investigation of urine samples from occupationally styrene-exposed workers (11 males, six females) and an unexposed control group. Phenylethyleneglycol enantiomers and 2-phenylethanol were present in the urine samples of exposed and unexposed individuals whereas 1-DL-phenylethanol was not found in control urine. The L/D enantiomer ratio of phenylethyleneglycol was found to be approximately 3 in the exposed group and 1.5 in the control group. Because of the close structural relation of these metabolites to the primarily formed epoxide, the results give further insight into the stereotoxicity of styrene in man.

A 90-day vapor inhalation toxicity study of decalin

A subchronic 90-day inhalation study was conducted to determine the toxic effects of decalin, a commonly used industrial solvent. Experimental groups consisting of male and female beagle dogs, male and female Fischer-344 rats, and female C57BL/6 mice were continuously exposed to decalin concentrations of 5 or 50 ppm. An unexposed control group was also maintained. All dogs and a portion of each rodent group were sacrificed and examined at exposure termination, while the remaining rodents were held for observation up to 21 months postexposure. No distinct exposure-related lesions were noted in dogs. Dog body weights, organ weights, and blood clinical pathology were also normal. At exposure termination hepatocellular cytoplasmic vacuolization was noted in female mice exposed to both concentrations. This liver tissue change was reversible and was not a significant finding in female mice examined during the 21-month postexposure observation period. In male rats, decalin exposure produced nephropathy characterized by hyaline droplets, necrosis, and intratubular casts. Accentuated tubular degeneration and medullary mineralization were noted in exposed rats held for long-term postexposure observation. There was no associated abnormal increase in mortality nor alterations in serum, blood urea nitrogen, or creatinine levels. Female rats were free of decalin-induced renal damage. There was a slightly greater incidence of commonly occurring pituitary tumors in both mice and rats; however, the tumor incidence was not dose related. The results of this study suggest that the toxic effects of decalin are similar to those previously described for other hydrocarbon solvents and fuels.

Homing of coho salmon ( Oncorhynchus kisutch) exposed to morpholine

Smolts of coho salmon ( Oncorhynchus kisutch) were exposed to 5 × 10 −5 mg·l −1 morpholine for 15 days and released into the Salmon River along with an unexposed control group. During the following two autumns, morpholine was introduced into the hatchery's fish ladder on various days and the return of experimental fish was recorded. The returns of morpholine-exposed and control fish were not statistically different. With morpholine present in the fish ladder, control fish were not repelled, and with morpholine absent from the ladder, morpholine-exposed fish returned as readily as control fish.

Sister-chromatid exchanges in association with occupational exposure to ethylene oxide

Sister-chromatid exchange (SCE) frequencies in employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. Three worksites where the previous environmental control of ETO was known to have differed were chosen. Within these worksites, subjects were categorized into high potential exposed, low potential exposed and control groups. An additional community control group was obtained. Blood samples for chromosomes studies of peripheral lymphocytes were dawn at several time points over a period of 24 months. The effects on SCE of age, sex, smoking habits and reader variation were considered. Worksites I, II and III, respectively, represented increasing levels of exposure. At Worksite III large differences among groups persisted over 24 months. At Worksite II, the SCEs in the high potential exposed workers were higher than those in the other groups. At no time was the low potential exposed group at Worksite II statistically significantly higher in mean SCE than the worksite controls. No consistent differences among groups were noted in Worksite I.

Amines: possible causative agents in the development of bronchial hyperreactivity in workers manufacturing polyurethanes from isocyanates.

Investigations of respiratory symptoms among workers in a factory producing polyurethane foam included measurement of air pollution with amines and isocyanates and a simultaneous health investigation of the exposed workers. An increased bronchial reactivity to inhaled methacholine was found in the study group compared with two unexposed control groups. This finding, together with visual disturbances in the exposed group, were assumed to be caused mainly by the volatile amines. The concentrations of isocyanates in air were well below 0.005 ppm. The amine concentration was 1000 to 10 000 times higher than the isocyanate concentration. The most volatile amine, N-methylmorpholine, occurred in the air in concentrations higher than 10 ppm. The results indicate that not only the isocyanates but also the amines might well be responsible for respiratory symptoms among exposed workers in polyurethane foam production.

In vivo and in vitro ethylene oxide exposure of human lymphocytes assessed by chemical stimulation of unscheduled DNA synthesis

Factory workers exposed to ethylene oxide (EO), 0.5–1.0 ppm in factory air, together with matched controls from the same factory, were examined for evidence of toxic exposure by measurement of unscheduled DNA synthesis (UDS) induced by N-acetoxy-2-acetylaminofluorene (NA-AAF) and of chromosome aberrations in peripheral lymphocytes. The total chromatid gaps plus breaks were significantly elevated and NA-AAF-induced UDS was significantly reduced in the EO-exposed group as compared with the unexposed control group. The NA-AAF-induced UDS values negatively correlated to the duration (yr) of EO exposure ( r = −0.45, p < 0.02) and the number of chromosome breaks ( r = −0.61, p < 0.05), indicating an inhibition in vivo of DNA-repair capacity by EO. These data were verified in vitro by biochemical and autoradiographic studies of EO-induced UDS in human blood cells. Above 2 mM EO, UDS was inhibited in lymphocytes whether they were cultured for 24 or 122 h after alkylation with EO. Even at the subtoxic EO dose of 0.1 mM, lymphocytes were sensitized to additional exposures of NA-AAF, so that cytotoxicity was increased to 40% compared with 5% for the controls even though UDS was unaffected. It is concluded that EO was toxic to lymphocytes, even when they were sensitized at non-toxic EO doses to the cytotoxic action of other mutagens (e.g. NA-AAF), and the cells that did survive above 2 mM EO were inhibited in their DNA-repair capacity as judged by reduced UDS.

Parasite Population Regulation: Lethal and Sublethal Effects of Leptorhynchoides thecatus (Acanthocephala: Rhadinorhynchidae) on Hyalella azteca (Amphipoda)

The hypothesis that Leptorhynchoides thecatus populations are regulated by mortality of heavily infected intermediate hosts, Hyalella azteca, was examined experimentally. Mortality related to the infection process could not be demonstrated because no survivorship difference occurred between amphipod groups exposed to L. thecatus and unexposed control groups after 24 hr. Likewise, amphipod mortality could not be associated with infection intensity during this period. Amphipod mortality, growth, and infection intensity were monitored for 25 days after a 24-hr exposure period. Cystacanths were infec- tive to fish after 25 days. Survivorship of exposed amphipods was at least as great as that of unexposed controls. Infection intensity in exposed male survivors did not differ significantly from that in males that died during the study. Infection intensities in females and survivors of undetermined sex were signifi- cantly higher than in Hyallela that died. The effect of time on amphipod size (as indicated by head length) was significant for male survivors and all females, but not for males that died. No negative effect of infection intensity on growth was demonstrated, nor was there significant correlation between amphipod size and infection intensity for either sex of amphipod at any time during the 25-day experiment. No evidence of lethal effects or sublethal effects on growth was detected.

Urinary Cytologic Examinations of Laboratory Workers

An apparent excess of abnormal urine cytological findings in crime laboratory workers exposed to potentially carcinogenic aromatic amines was investigated by a cross-sectional epidemiologic study comparing these workers with an unexposed control group. The prevalence of atypical findings in the laboratory workers exceeded that in the control group; however, the results were not statistically significant. A number of serious problems were identified including a high prevalence of inflammatory changes (25% to 26%) and a moderately high percentage of atypical changes (2.5% to 5.4%) in the control population, failure to detect (on urological workup) evidence of neoplastic disease of the urinary tract in any of the laboratory workers whose urine examinations were cytologically interpreted as either atypical or neoplastic cells, and difficulty in determining proper referral criteria for urological workup.

Morbidity studies of workers exposed to whole body vibration.

Insurance claims for medical services submitted on behalf of a group of workers in the construction industry were collected over a 20-month period. The morbidity experience of those workers exposed to whole body vibration was contrasted with that of an unexposed control group eligible for benefits under the same plan. Using Mantel-Haenszel adjustment for age and experience, a significantly elevated relative risk was found among the exposed group in three of the thirty disease categories studied. In no disease category did the control group possess a significantly higher risk of requiring medical services. A striking proportion of the disease categories showed an initial increase in risk for exposed workers followed by a decrease with experience. This pattern suggests a selection process in which workers leave exposed-group jobs as they become afflicted with certain disease conditions.

The application of electrodeposition techniques to flameless atomic absorption spectrometry : Part III. The determination of cadmium in urine

Cadmium in urine can be determined by a simple flameless atomic absorption technique, in which the metal is electrolyzed onto a thin platinum wire, followed by electrical heating of the wire. The technique is compared with the well-established flame procedure, involving extraction with APDC into MIBK. The data obtained by the two techniques are in good agreement. Large individual variations occur in the urinary concentration of cadmium for workers suspected of cadmium exposure. The group mean values for these workers lie in the range 4–5 p.p.b.; mean values for unexposed control groups are around 1 p.p.b. On a group basis, the results indicate a significantly higher urinary excretion of cadmium for the workers than for the control groups.

The reaction of pregnant ewes to inoculation with mucosal disease virus of bovine origin

The pathogenicity of three bovine strains of mucosal disease (MD) virus ( V TOB ; V JGM and V E ) was tested in ewes 79 to 87 days after mating. All three strains grew to a high titre in the placentomes; mean titres of 10 6·7 TCID 50 per g. in those inoculated with V TOB , 10 6·4 TCID 50 per g. with V JGM and 10 4·9 TCID 50 per g. with V E . Although high titres were found in some foetal tissues it was difficult to determine if virus multiplication had taken place in them. Of the ewes allowed to lamb, 7 of the 8 lambs born to ewes inoculated with V TOB were born dead, and 6 were born 10 to 27 days prematurely; 4 of the 8 born to ewes inoculated with V JGM were born dead and 2 were born 10 and 38 days prematurely. One of the 6 born to ewes inoculated with V E was born dead. When ewes 24 to 46 days after mating received V TOB strain either i.v. or i.n., none of the ewes gave birth to live lambs although an unexposed control group produced 186·0 per cent. of live lambs. The histological changes suggest that foetal death results from loss of intimate contact between the foetal and maternal placentomal layers due to thrombosis, necrosis and inflammatory changes within the intercryptal villi with subsequent degenerative changes in the chorionic epithelium.