Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.

It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p'-dichlorodiphenyldichloroethylene, chlordane-related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01-3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p-interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45-55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.

Beta-alanine transaminase activity in black and suppressor of black mutations of Drosophila melanogaster.

An assay for beta-alanine transaminase activity in extracts of Drosophila melanogaster has been developed. By use of this assay, the levels of beta-alanine transaminase activity in several strains of flies has been examined as a function of developmental age. The black mutation shows elevated levels of activity compared to wild type, while suppressor of black strains show decreased levels compared to wild type.

Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk.

Numerous studies have examined the relationship between organochlorines and breast cancer, but the results are not consistent. In most studies, organochlorines were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. Therefore, a hospital-based case-control study was conducted in Ontario, Canada to evaluate the association between breast cancer risk and breast adipose tissue concentrations of several organochlorines. Women scheduled for excision biopsy of the breast were enrolled and completed a questionnaire. The biopsy tissue of 217 cases and 213 benign controls frequency matched by study site and age in 5-year groups was analyzed for 14 polychlorinated biphenyl (PCB) congeners, total PCBs, and 10 other organochlorines, including p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene. Multiple logistic regression was used to assess the magnitude of risk. While adjusting for age, menopausal status, and other factors, odds ratios (ORs) were above 1.0 for almost all organochlorines except five pesticide residues. The ORs were above two in the highest concentration categories of PCB congeners 105 and 118, and the ORs for these PCBs increased linearly across categories (Ps for trend < or =0.01). Differences by menopausal status are noted especially for PCBs 105 and 118, with risks higher among premenopausal women, and for PCBs 170 and 180, with risks higher among postmenopausal women. Clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue.

Feeding and urine cotinine values in babies whose mothers smoke.

In Canada, 8% to 20% of infants are breast-fed by mothers who smoke. To determine whether breast-feeding increases infants' exposure to tobacco smoke products, urinary cotinine excretion was measured in 172 babies, 33 of whom were breast-fed. A milk sample was taken from the mothers who were breast-feeding, and cotinine was measured with gas chromatography. The breast-fed babies had a median cotinine to creatinine ratio of 433 ng/mg, whereas the bottle-fed babies' median was 200 ng/mg (P less than 10(-4)). Similar differences were observed after adjustment for the number of cigarettes smoked by the mother and by other smokers in the home in the previous 24 hours. The correlation coefficient between the number of cigarettes smoked by the mother and the breast milk cotinine concentration was significant (r = .69, P = 2 X 10(-4)). Moreover, urine cotinine values from the breast-fed babies increased with higher concentrations of cotinine in the mother's milk (r = .56, P = .02). These results provide evidence that breast-feeding increases exposure to tobacco smoke components in infants whose mothers smoke. This is yet another argument for strongly encouraging women who smoke to stop smoking during pregnancy and lactation.

Exposure of remote maritime populations to coplanar PCBs.

Two remote maritime populations were evaluated for their biological exposure to organochlorines in 1989-1990. Because of their high intake of seafood, these two populations have high biological levels. One hundred nine breast milk samples from Inuit women from Arctic Québec were analyzed to determine levels of polychlorodibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) including non-ortho, mono-ortho, and di-ortho congeners. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEqs) for PCBs were 3.5 times higher in Inuit milk samples than in 96 Caucasian milk samples. Among the 185 fishermen from the Lower North Shore of the Gulf of the St. Lawrence River, we evaluated 10 highly exposed fishermen for their coplanar PCB blood levels. Total TEqs were 900 ng/kg for highly exposed individuals with 36 ng/kg for controls. In these two nonoccupationally exposed populations, coplanar PCBs make a larger contribution to the TEq than PCDDs and PCDFs. However, the mono-ortho penta CB No. 118 is the major contributor for the total toxicity.

Epidemiologic study of renal function in copper smelter workers.

A medical cross-sectional examination of a copper smelter work force was undertaken after environmental contamination with lead, cadmium and arsenic had been documented. A total of 920 subjects was examined, including active smelter employees, retired workers and copper mine employees who had never worked in the smelter. Slight to moderate absorption of lead and cadmium was definitely present in the active copper smelter employees, who had significantly higher levels of Pb-B, ZPP and Cd-B than retired employees and miners. Cd-U levels were higher in retired workers, who were also older and had, as a group, longer duration of exposure in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the level considered critical for nephrotoxicity, in any of the subjects. Median Cd-B level for active workers was 2.75 micrograms/L. Lead absorption was characterized by a relatively small proportion (16.7%) of active employees with Pb-B levels 40 micrograms/dL or higher. We were particularly interested in exploring the possibility that simultaneous exposure to lead and cadmium, although at levels not associated with nephrotoxicity for each metal separately, could result in renal function impairment. Distribution patterns of BUN and serum creatinine levels were unremarkable. Urinary beta 2-microglobulin levels were less than 200 micrograms/g creatinine in 95% of copper smelter employees. There were no significant correlations between urinary beta 2-microglobulin levels and Cd-U, Cd-B, Pb-B and ZPP or between urinary beta 2-microglobulin excretion and serum creatinine or BUN levels. Urinary beta 2-microglobulin levels were significantly correlated with age in the copper smelter workers, but not in the miners. Nevertheless, in the absence of any significant correlations between urinary beta 2-microglobulin and Cd-U, Cd-B, a causal relationship with cadmium absorption cannot be affirmed. That kidney function could be impaired by long-term exposure in the smelter was only indirectly suggested. Effects on renal function at the low levels of cadmium and lead absorption that were observed in this smelter population are minimal.

Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland.

Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher than those measured using the same analytical method in samples from Canadians in Quebec City, Quebec. Brain lipids contained lower concentrations of all organochlorines than lipids extracted from other tissues. Organochlorine residue levels in lipid extracts from liver, omental fat, and subcutaneous abdominal fat samples were similar, with the exception of ss-hexachlorocyclohexane, which reached a greater concentration in liver lipids than in lipids from both adipose tissues (4-fold; p < 0. 05). Comparisons with available international data on adipose tissue levels reveal that the organochlorine body burden in the Inuit population of Greenland is presently among the highest resulting from environmental exposure.

Effect of transient moderate hyperventilation on dynamic cerebral autoregulation after severe head injury.

OBJECTIVE: This study was undertaken to evaluate the effect of acute moderate hyperventilation on cerebral autoregulation in head-injured patients. METHODS: Dynamic cerebral autoregulation was analyzed by use of transcranial doppler ultrasonography before and after hyperventilation in 10 patients with severe head injury. All of the patients were artificially ventilated and underwent continuous monitoring of arterial blood pressure, intracranial pressure, and end-tidal carbon dioxide. To test autoregulation, rapid transient decreases in systemic blood pressure were achieved by quickly releasing large blood pressure cuffs that were inflated around both thighs. This resulted in a drop of 24 +/- 6 mm Hg in mean systemic blood pressure, which lasted an average of 49 +/- 24 seconds. Cerebral blood flow velocity was monitored continuously in both middle cerebral arteries by use of transcranial doppler ultrasonography. The percentage change in middle cerebral artery velocity was used as an index of the change in cerebral blood flow during the autoregulatory response. The change in estimated cerebrovascular resistance, immediately after the blood pressure drop, or the rate of regulation was used to analyze the effectiveness of the cerebral autoregulation. This value was calculated by determining the rate of increase in middle cerebral artery velocity during the 1st 5 seconds after a blood pressure drop, relative to the rate of increase of the cerebral perfusion pressure. RESULTS: The average rate of regulation during normocapnia at pCO2 of 37 mm Hg was 11.4 +/- 5% per second. After reduction of the pCO2 to 28 mm Hg, the average rate of regulation improved significantly (P < 0.001) to 17.7 +/- 6% per second. Autoregulation improved, despite no significant change in the cerebral perfusion pressure during hyperventilation. The degree of improvement in autoregulation was significantly correlated with the CO2 reactivity (r = 0.45, P < 0.05) but did not correlate (r = -0.23, P = 0.33) with the change in arterial pH value after hyperventilation. CONCLUSION: These results confirm the finding that dynamic autoregulation is disturbed in severe head injury and that moderate transient hyperventilation can temporarily improve the efficiency of the autoregulatory response, probably as a result of a transient increase in vascular tone.

Surgical resection of epileptogenic cortex associated with structural lesions.

In this article we have reviewed the available data for postsurgical seizure control in patients with both structural lesions and seizures. There is evidence that simple excision alone will control seizures in some patients, whereas others require, in addition, seizure surgery with resection of epileptogenic cortex. When available studies are reviewed and submitted to meta-analysis, however, we have found that more patients are seizure free at 2-year follow-up after seizure surgery than after simple excision. Seizure control is one of the many factors that influence the choice of surgical approach. Therefore, we do not recommend that all patients with structural lesions and seizures disorders undergo seizure surgery. Rather, for those patients with a structural lesion in whom seizures are medically intractable, our review supports excision of the structural lesion as well as resection of the epileptogenic cortex to provide the patient with the best opportunity of seizure control.

An interlaboratory comparison programme for several toxic substances in blood and urine.

Since 1979, the Centre de Toxicologie du Québec has operated an interlaboratory comparison programme for several toxic substances in blood and urine. We initiated this program due to the unavailability of reliable and representative reference materials for toxic elements in blood and urine. The main objective is to enable participants to improve or maintain the accuracy of their analytical work by periodically comparing their results. There are presently 76 laboratories registered in the programme for one or more substances. The majority are located in North America with several others in Europe and South America. Available substances include lead and cadmium in blood, aluminum in serum, and mercury, arsenic, cadmium, fluoride and chromium in urine. Samples are prepared by pooling specimens obtained from exposed workers. We have examined the performance of participants over the course of the years using as criteria the deviation from the target value, the scatter of results and the proficiency within preset limits of toxicological significance. Whenever possible the influence of analytical methods was evaluated. The feedback provided by participation in the programme appears to be a significant factor in the maintenance or improvement of analytical proficiency. The vast majority of participants obtain results of adequate reliability for use in the monitoring of exposed workers.

Blood and urinary cadmium levels in Inuit living in Kuujjuaq, Canada.

Blood and urine cadmium concentrations have been determined in a group of 85 Inuit residents of Kuujjuaq, Quebec, Canada, drawn from actively hunting households. Mean blood cadmium values are high at 39.4 nmol/l, varying between 6.6 in non-smokers and 60.3 in smokers. No association of blood cadmium with self-reported offal consumption could be found. Median urine cadmium concentrations are elevated at 2.3 mumol/mol creatinine and rise substantially with age: 0.9 in the 30-39 age group; 3.2 among the 40-59 age group; and 4.1 in the 60 and over.

New patterns of drinking-water consumption: results of a pilot study.

A pilot study on water consumption was carried out in the Québec City region in April and May 1996 with 125 people using a 24-h recall plus a 2-day diary. Consumption of drinking water via liquid and food was assessed as well as the type of water consumed (tap, bottle or filtered water) and place of consumption (home or away from home). Most of the people (56%) were drinking some bottled water or filtered tap water and 25% of water intake was away from home. Food consumption was found to be a non-significant source of drinking-water intake. The average water consumption was nearly similar in exclusively tap-water consumers and bottled- or filtered-water consumers (1.5 vs. 1.7 l/day, P = 0.29) but two-thirds of the consumption in this last group is natural water, while it is mixed water in the bottled/filtered-water group. No significant difference in amounts consumed were found according to age, but older people drank hot beverages and soup more often. The present pilot-study was weakened by a low participation rate (14%). Incentive might be necessary to improve participation rate and data collection methods must also be simplified. A 24-h recall plus a 1-day diary seem sufficient and data on consumption could be limited to liquids, soups and cereals.

Pattern of cadmium contamination in the liver and kidneys of moose and white-tailed deer in Québec.

Samples of moose (N = 431) and white-tailed deer (N = 225) liver and kidneys were collected during the 1985 hunting season from 14 zones south of the 50 degree latitude in Québec. Regional differences in cadmium level in the liver were detected and three homogeneous areas were delineated for each species. Uptake was greater for moose than for deer: in the liver, mean concentrations were 2.9-15.9 mg kg-1 (dry weight) for moose and 0.8-2.6 for deer, depending on the area and sex; in kidneys, means ranged between 31.8-100.5 and 20.9-39.0 mg kg-1, respectively. Female moose had lower levels than bulls. Less affected moose, in eastern Québec, contained cadmium concentrations comparable to the highest values measured in Scandinavia. Cadmium uptake in deer was on the same level or higher than in the United States. Our results indicate a widespread presence of this heavy metal in the environment that may be linked to acid precipitation. We do not recommend consuming wild cervid liver or kidneys in Québec for the moment. Further research is needed on the overall mechanisms involved in the cadmium contamination of the environment and on the actual intake of this metal in the human diet.

Variation in cadmium content of caribou tissues from northern Québec.

Samples of kidney, liver, skeletal muscle, heart, mesentery and rumen wall were collected during 1985-1986 in northern Québec from 121 caribou belonging to the Rivière George herd. Significant seasonal variations were found for cadmium concentration in kidneys, liver and skeletal muscles, the level being higher in winter than in autumn. The concentration in liver and kidneys increased with age, while the effect of this factor was complex in skeletal muscles. Sex-related differences were found in muscle and liver levels of cadmium. According to season, sex and age, mean dry-weight concentrations varied between 5.6 and 51.3 micrograms g-1 in kidneys, 1.7 and 4.0 micrograms g-1 in liver and 0 and 0.27 microgram g-1 in skeletal muscles. Season and sex-related differences could be explained by seasonal variation in cadmium intake and by the annual weight cycle exhibited by caribou kidneys and liver. Because of the relatively high cadmium content, it was recommended not to consume liver and kidneys of free-ranging caribou in Québec; this restriction did not apply to meat, heart, mesentery or rumen wall that contained limited concentrations of this heavy metal.

Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds.

During the past 20 years a number of studies have found neurological and immunological effects in the developing fetus and infants exposed to background or only slightly elevated levels of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). To address concerns arising from possible increased human exposure in the Arctic and possible effects of POPs, all circumpolar countries agreed in 1994 to monitoring of specific human tissues for contaminants in the Arctic under the Arctic Monitoring and Assessment Program (AMAP). Mothers in eight circumpolar countries contributed blood samples that were analysed at a single laboratory for 14 PCB congeners (IUPAC No. 28, 52, 99, 105, 118, 128, 138, 153, 156, 170, 180, 183, 187) and 13 organochlorine pesticides (aldrin, beta-hexachlorocyclohexane (beta-HCH), dichlordiphenyltrichloroethane (p,p'-DDT), diphenyldichloroethylene (p,p'-DDE), dieldrin, heptachlorepoxide, hexachlorobenzene (HCB), mirex, and the chlordane derivatives alpha-chlordane, gamma-chlordane, cis-nonachlor, oxychlordane and trans-nonachlor). Inuit mothers from Greenland and Canada have significantly higher levels of oxychlordane, transnonachlor and mirex than mothers from Norway, Sweden, Iceland and Russia. Inuit mothers from Greenland also have significantly higher levels of these contaminants than Inuit mothers from Canada and Alaska. These differences among Inuit groups may represent regional dietary preferences or different contaminant deposition patterns across the Arctic. Levels of PCBs are also elevated among some arctic populations due to their consumption of marine mammals and are in the range where subtle effects on learning and the immune system have been reported. The Russian mothers who consume mainly food imported from southern Russia have elevated levels of DDT, DDE, beta-HCH and a higher proportion of lower chlorinated PCB congeners. This study has allowed an assessment of the variation of contaminants such as PCBs and various organochlorine pesticides (DDT, chlordane, etc.) in human populations around the circumpolar north.

Determination of heroin, 6-acetylmorphine, and morphine in biological fluids using their propionyl derivatives with ion trap GC-MS.

We present an analytical method for the determination of heroin, free 6-acetylmorphine (6-AM), and free morphine in blood, urine, and vitreous humor. This method is used in postmortem cases where heroin is the suspected cause of death. The analytical protocol includes the following steps: liquid-liquid extraction at pH 9.5, propionylation at room temperature of 6-AM, and morphine by propionic anhydride using 4-dimethylaminopyridine as catalyst. Neither heroin nor diethylnalorphine (internal standard) is transformed during this derivatization. The reaction products are analyzed using full-scan (250-405 amu) ion trap gas chromatography-mass spectrometry. This method provides a baseline separation and distinctive mass spectrum of each compound of interest. Reproducibility and an evaluation of analysis parameters are also presented.

Quantitative determination of carbon monoxide in blood by head-space gas chromatography.

The gas chromatographic determination of carboxyhemoglobin in blood has been improved by the use of a head space technique to measure the carbon monoxide (CO) released from blood. To improve sensitivity, the CO is reduce to methane before detection by the flame ionization detector (FID). The time for a single determination is reduced to five minutes by backflushing the column as soon as the methane has been eluted. This automated procedure is suitable for routine analysis of large batches of samples. Results are compared with those obtained using a CO-Oximeter.

Is there a need for systematic blood lead screening in Canadian children?

Neuropsychological effects occurring in young children exposed to low blood lead levels are now better known. This paper reviews the need to systematically screen for blood lead levels compatible with subclinical lead poisoning in young Canadian children. Using standard criteria for judging the appropriateness of this measure, the authors found no evidence to support such a practice in Canada. Case-finding is recommended in clinical settings for children with disorders suggestive of lead poisoning, increased lead absorption or exposure to a potential source of lead. A population survey is also recommended in the presence of a well-documented community environmental lead source. There is a need for common protocols across Canada for evaluating and treating children with blood lead levels compatible with subclinical poisoning. Areas of priority research are: the impact of persistent environmental sources of lead such as old paint and lead in water; defining criteria for selective screening; and methods of cost-effective environmental remediation.

Smoking during labour.

Smoking in hospitals is now forbidden. In several hospitals, however, women in labour are allowed to smoke in designated smoking areas. This study assesses whether smoking during labour increases the carboxyhaemoglobin concentrations in maternal and cord blood, taking into account the number of cigarettes smoked during pregnancy, duration of labour and parity. Women were questioned on their smoking behaviour shortly after delivery. A total of 295 mother-infant pairs were included in the study. Of the 94 (31.9%) smokers, 33 smoked during labour at home only and 34 during labour at the hospital. For newborns of smokers, the daily ration of cigarettes smoked by the mother during pregnancy and the number smoked during labour explained respectively 10.4% and 10.8% of the residual variance of carboxyhaemoglobin in cord blood. Smoking during labour significantly increases carboxyhaemoglobin levels. It should be prohibited in hospitals.

[Biological monitoring of exposure to polycyclic aromatic hydrocarbons among people living nearby an aluminum smelter in the province of Québec]. / Surveillance biologique de l'exposition aux hydrocarbures aromatiques polycycliques chez des personnes vivant aux environs d'une aluminerie québécoise.

BACKGROUND: The objective of the study is to estimate the exposure to pyrene, an indicator of polycyclic aromatic hydrocarbons (PAHs) in the general environment, by using the internal dose of 1-hydroxypyrene (1-OHP) among people living nearby an aluminium smelter in the Montérégie area, Province of Québec, Canada. METHODS: This cross-sectional study was done in November and December 1998. Participants were randomly selected according to their environmental exposure to PAHs and were distributed according to three exposure levels (high, low, none). Altogether, 121 non smokers aged between 18 to 70 years were recruited for the study. Persons occupationally exposed to PAHs or using tar-based medications were excluded. Those with personal medical conditions that affect the metabolism of pyrene were also excluded. Urine samples were taken in the morning and analysed by gas chromatography and mass spectrometry (GC-MS) to determine the concentration of the metabolite, 1-OHP. RESULTS: Among the exposed group (n=78), the geometric mean of urinary concentration of 1-OHP was 0.073 micromol/mol creatinine compared to 0.060 micromol/mol creatinine for the control group (n=40). The difference did not reach statistical significance (p=0.09). Geometric means among the three groups of exposure (high, low, none) were respectively 0.079, 0.067 and 0.060 micromol/mol creatinine (p=0.13). Accounting for personal risk factors, such as diet, passive smoke, use of wood heating and time spent at home during the three days prior to urine sampling, did not change previous results. CONCLUSION: This study indicates that the environmental levels of PAH produced by this factory are low and do not contribute significantly to the body burden of PAH as measured by 1-OHP.