Males occupational exposure

Central nervous system stimulation similar to that reported for occupational exposure is seen following acute dermal exposure to endosulfan in experimental animals. The spectrum of effects includes hyperexcitability, tremors, decreased respiration, tonic-clonic convulsions, and ultimately death (Gupta and Chandra 1975 Hoechst 1989b Nicholson and Cooper 1977). In rats, the lowest doses associated with these effects were 16 mg/kg/day in females and 250 mg/kg/day in males during a 6-hour/day, 5-day exposure regimen (Hoechst 1989b). 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

Mineral Oil Hydraulic Fluids. Studies regarding cancer in humans or animals after inhalation exposure to mineral oil hydraulic fluids were limited to a single case-control study that examined associations between subjectively reported occupational exposure to petroleum-derived liquids and cancer at particular sites among 3,726 male cancer patients (Siemiatycki et al. 1987a). The study found no convincing associations between occupational exposure to hydraulic fluids and cancer at any site. This study is discussed in more detail in Section 2.2.3.8, because, while inhalation exposure was probable for the subject occupations, the authors reported that the exposure route was more often dermal contact. 

Selected studies are discussed below and include reports on occupational exposure to lead for females and males followed by environmental (low level) exposure to lead in females and males. 

Winder C. 1989. Reproductive and chromosomal effects of occupational exposure to lead in the male. Reprod Toxicol 3 221-233. 

Figure 1. The age-specific incidence of lung cancer deaths in male cigarette smokers and nonsmokers (Kahn, 1966, Appendix Table A). The lifetime incidence for nonsmokers includes lung cancers attributable to passive smoking, asbestos inhalation, and other occupational exposures.

Occupational exposures and the study with human volunteers indicate that exposures at low concentrations cause headaches and signs of central nervous system depression. No headaches were reported and no equilibrium disturbances were measured during occupational exposures of healthy workers to Otto Fuel II (measured as PGDN) at concentrations <0.22 ppm (average of approximately 0.06 ppm) for periods of 30-60 min, although subtle changes in eye movements were recorded (Horvath et al. 1981). In a study with healthy but previously unexposed male volunteers, the threshold for odor detection was 0.2 ppm (Stewart et al. 1974). Mild headaches were reported in one of three subjects after a 6-h exposure at 0.1 ppm, in two of three subjects after a 2-h exposure at 0.2 ppm, and in one of three subjects after a 1-h exposure at 0.5 ppm. Severe headaches occurred after an 8-h exposure at 0.2... 

The odor threshold, 0.58 ppm to 5.0 ppm (Amoore and Hautala 1983 Ruth 1986) is low compared with irritant or toxic concentrations. No acute exposures were located resulting in mild effects in humans. Three monitoring studies, involving no symptoms to mild symptoms during chronic occupational exposures of adult males, are relevant to development of AEGL-1 values. The symptoms and blood concentrations of cyanide in the monitoring study of Chandra et al. (1980) indicate that the workers may have been exposed at higher atmospheric concentrations than those reported. 

As noted above for the AEGL-1, chronic occupational exposure of adult males to >10 ppm produced symptoms of headache, weakness, changes in taste and smell, irritation of the throat, vomiting, and effort dyspnea (El Ghawabi et al. 1975 NIOSH 1976 Blanc et al. 1985). For a few individuals, chronic exposures occasionally produced more serious adverse effects, such as fainting and psychotic episodes. There was no evidence that these symptoms occurred after one exposure. A concentration of >25 ppm for 1 h resulted in numbness, weakness, vertigo, nausea, rapid pulse, and flushing of the face (Parmenter 1926). Only one individual was involved, and neither the exposure duration nor the concentration were measured. 

Occupational exposure to chlordecone for up to 1.5 years caused oligospermia and decreased sperm motility in male workers. However, no loss of fertility was reported by the workers (Guzelian 1982a Taylor 1982, 1985 Taylor et al. 1978). Refer to Section 2.2.1.5 for further details. 

Barchielli A, Buiatti E, Franchini M, et al. 1982. Male infertility and occupational exposure to chemical agents A review. Med Lav 73 483-495. 

Meyer CR. 1984. Critical review of studies relating occupational exposures of males and reproductive capacity. In Lockey JE, Lemasters GK, Keye WR Jr, eds. Reproduction The new frontier in occupational and environmental health research. New York, NY Alan R. Liss, Inc., 375-384. 

Schrag SD, Dixon RL. 1985. Occupational exposures associated with male reproductive dysfunction. Annu Rev Pharmacol Toxicol 25 567-592. 

Occupational exposure to 1,2-dibromoethane has been reported to produce adverse effects both on spermatogenesis (sperm concentration) and seminal fluid production (semen volume) in human males (Ratcliffe et al. 1987 Takahashi et al. 1981, Ter Haar 1980). 

No studies were found correlating levels to which humans were exposed with actual body burdens. However, an attempt was made to correlate blood levels of chlordane, which may contain from 6% to 30% heptachlor, to duration of occupational exposure. Blood samples from 51 male pest control operators who were occupationally exposed to chlordane were tested for the presence of chlordane and its metabolites trans-nonachlor, oxychlordane, and heptachlor epoxide. The blood of 19 male workers with no experience spraying chlordane was also tested as a control. Heptachlor epoxide was detected (from not detectable to 1.6 ppb) in 20% of the blood samples from pest control operators exposed to chlordane (concentration not reported). The total chlordane in the blood was low but demonstrated sizable correlation with the number of spraying days and the amount of chlordane sprayed (Saito et al. 1986). 

Mommsen S, Aagard J. 1984. Occupational exposures as risk indicator of male bladder carcinoma in a predominantly rural area. Acta Radiol 23(2-3) 147-152. 

Hamill Py Steinberger E, Levine RJ, Rodriguez-Rigau LJ, Lemeshow S, Avrunin JS The epidemiologic assessment of male reproductive hazard from occupational exposure to TDA and DNT. J Occup Med 24 985-993, 1982... 

Occupational exposure of 12 male workers, whose hands were in contact with MDA several hours per day, caused toxic hepatitis. The clinical pattern of the cases included right upper quadrant pain, high fever, and chills with subsequent jaundice. A skin rash was seen in five of the cases. Percutaneous absorption was considered to be the major route of exposure because workers in the same occupational setting who did not have direct skin contact with MDA were not affected. All patients recovered within 7 weeks, and follow-up more than 5 years later showed no biochemical or clinical evidence of chronic hepatic disease. 

The possible carcinogenicity of nitrous oxide has been studied in dentists and chairside assistants with occupational exposures. No effect was observed in male dentists, but a 2.4-fold increase in cancer of the cervix in heavily exposed female assistants was reported. Other epidemiological reports of workers exposed to waste anesthetic gases have been negative. Carcinogenic bioassays in animals have yielded negative results. Nitrous oxide was not geno-toxic in a variety of assays. ... 

Lead exposure can produce a number of other effects. One of the most common effects is on the red blood cells, which results in anemia. The red blood cells become fragile and hemoglobin synthesis is impaired. Changes in the red blood cells and some enzymatic changes were used as a marker for lead exposure. Similar to other metals, lead adversely affects kidney function, but this is now rare with reductions in occupational exposure. Several studies have demonstrated that elevated lead exposure is related to elevated blood pressure levels, particularly in men. There appears to be a weak association between lead exposure and increased incidence of lung and brain cancer. Lead exposure is a reproductive hazard for both males and females. In males, lead affects sperm count and sperm motility, resulting in decreased offspring. 

Chemicals can also directly affect male reproductive organs or sperm. Decreased sperm count, decreased sperm motility, or abnormalities can result in male sterility or reduced fertility. For example, occupational exposure to lead can result in infertility due to sperm abnormalities. Male sterility can also result from exposure to the fungicide dibromochloropropane (DBCP). Drugs or chemicals, such as... 

Two studies were located that reported the occurrence of liver cancer in humans exposed to carbon tetrachloride fumes, both acutely (Tracey and Sherlock 1968) and for longer periods (Johnstone 1948). In the former case, a male died of hepatocellular carcinoma 7 years after acute intoxication with carbon tetrachloride at an age of 59, although he had a history of moderate alcohol consumption (without demonstrable liver cirrhosis). In the second case, a 30- year-old female died of "liver cancer" after 2-3 years of occupational exposure to carbon tetrachloride that was sufficient to produce signs of intoxication. However, this evidence is much too sparse to establish a cause-and-effect relationship. 

Hamster. Groups of 65-80 male or female Syrian golden hamsters, 12 weeks of age, were exposed by whole-body inhalation to 15 pg/m di(2-ethylhexyl) phthalate vapour (> 99% pure) for 24 h per day on five days per week until natural death. Total exposure over the lifetime was 7-10 mg/kg bw. No difference in survival was seen between controls and the di(2-ethylhexyl) phthalate-treated groups. Median survival in controls was 709 days in males and 507 days in females and that in treated animals was 703 days in males and 522 days in females. Tumour incidence was not increased in di(2-ethylhexyl) phthalate-treated hamsters (Schmezer et al., 1988). [The Working Group noted the low concentration and that it was selected to simulate occupational exposure.]... 

April 1977 to December 1984 there was a decrease in the male/ female sex ratio (26/48) in contrast, from 1985 to 1994, this ratio increased to normal values (60/64). These results suggest that high-level exposure to TCDD may affect birth sex ratios however, no changes in sex ratios have been observed as a result of parental occupational exposure to relatively high doses of TCDD,31 and no other data corroborate the Seveso findings. 

Cimetidine (for treatment of peptic ulcers) competes with dihydrotestosterone for receptors in the testis and accessory sex glands. The more common sequelae are low sperm count and gynacomastia. Epidemiological evidence has shown that occupation exposure to oral contraceptives can induce gynacomastia in exposed males. Diethylstilbestrol (DES) antagonizes the activity of fetal testosterone. In the male offspring, testicular hypoplasia, abnormal semen parameters, and infertility result. Ketoconazole has be shown to be transported to the seminal fluid and to immobilize the sperm. 

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