Growth in girls exposed in utero and postnatally to polybrominated biphenyls and polychlorinated biphenyls

BACKGROUND: Accidental contamination with polybrominated biphenyls (PBBs) of the Michigan food supply in 1973 led to the exposure of more than 4000 individuals and to formation of the PBB cohort registry (1976-1979). At enrollment, measurements were taken of serum PBB and polychlorinated biphenyl (PCB), possible endocrine disrupting chemicals. METHODS: We examined the association of estimated PBB and PCB exposure during pregnancy with current height and weight in 308 daughters, 5-24 years of age (mean age 15.2 years), born to women in the cohort. We estimated prenatal PBB exposure using maternal enrollment serum PBB and a model of PBB elimination. Prenatal PCB exposure was estimated using maternal enrollment serum PCB because background-level exposure through diet was ongoing. Self-reported height and weight were obtained from a 1997-1998 health survey. RESULTS: We found no association between prenatal PBB exposure and either daughter's current height or daughter's weight adjusted for height; however, prenatal PCB exposure above 5 parts per billion was associated with reduced weight adjusted for height. Exposure through breastfeeding did not modify the association. CONCLUSIONS: Mothers with PCB levels above the median had daughters whose current weights were 11 pounds lower than that of the daughters whose mothers had levels below the median. This study provides evidence that prenatal exposure to PCBs may affect growth.     

Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl

Accidental contamination of the Michigan food chain with polybrominated biphenyls (PBBs) led to the exposure of more than 4,000 individuals in 1973. Because PBB exposure is suspected to disrupt endocrine function, we assessed pubertal development in females 5-24 years of age (N = 327) who were exposed to PBB in utero and, in many cases, through breastfeeding. We estimated in utero PBB exposure using maternal serum PBB measurements taken after exposure (1976-1979) and extrapolated to time of pregnancy using a model of PBB decay. We found that breastfed girls exposed to high levels of PBB in utero (> or =7 parts per billion) had an earlier age at menarche (mean age = 11.6 years) than breastfed girls exposed to lower levels of PBB in utero (mean age = 12.2-12.6 years) or girls who were not breastfed (mean age = 12.7 years). This association persisted after adjustment for potential confounders (menarche ratio = 3.4, 95% confidence interval = 1.3-9.0). Perinatal PBB exposure was associated with earlier pubic hair stage in breastfed girls, but little association was found with breast development. The associations observed here lend support to the hypothesis that pubertal events may be affected by pre- and postnatal exposure to organohalogens.     

Endometriosis among women exposed to polybrominated biphenyls

PURPOSE: We examined the association between endometriosis and exposure to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) among women inadvertently exposed to PBBs in 1973. METHODS: Serum PBBs and PCBs were measured in the late 1970s. Women self-reported endometriosis at interview in 1997. We constructed Cox models to estimate the relative incidence of endometriosis in relation to PBB and PCB levels. RESULTS: Seventy-nine of 943 women (9%) reported endometriosis. Compared with women with low PBB exposure (or=4 ppb) (HR = 0.90; 95% CI, 0.51-1.59) exposure did not have increased incidence of endometriosis. Increased incidence of endometriosis was suggested among women exposed to moderate PCB (5-8 ppb) (HR = 1.67; 95% CI, 0.91-3.10) and high PCB (>or=8 ppb) (HR = 1.68; 95% CI, 0.95-2.98) levels compared with low PCB exposure (相似文献   

Breast-feeding among women exposed to polybrominated biphenyls in Michigan.

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.     

Mortality among workers exposed to polychlorinated biphenyls.

On the basis of evidence from animal studies, polychlorinated biphenyls (PCBs) are considered potentially carcinogenic to humans. However, the results of studies in human populations exposed to PCBs have been inconsistent. The authors conducted a retrospective cohort analysis (1957-1986) comparing the mortality of 3,588 electrical capacitor manufacturing workers with known exposure to PCBs with age-, sex-, and calendar time-specific mortality rates for all whites in the United States. Proportional hazards modeling was also performed to examine the association between cumulative PCB exposure and site-specific cancer mortality. All-cause mortality (192 deaths observed, 283.3 expected) and total cancer mortality (54 deaths observed, 63.7 expected) were lower than expected. More deaths were observed than expected for malignant melanoma (8 observed, less than 2.0 expected) and cancer of the brain and nervous system (5 observed, 2.8 expected). The average estimated cumulative dose for the cases of brain cancer (22.9 units) was greater than for other workers (12.9 units), but the 95% confidence intervals around this difference were broad. The risk of malignant melanoma was not related to cumulative PCB exposure. These results provide some evidence of an association between employment at this plant and malignant melanoma and cancer of the brain. The possibility that the results are due to chance, bias, or confounding cannot be excluded.     

Cytogenetic changes in persons exposed to polychlorinated biphenyls]

A cytogenetic study performed in a group of workers exposed to polychlorinated biphenyls comprised analysis of structural chromosomal aberrations in the lymphocytes in the first division in vitro, analysis of micronuclei frequency in binuclear lymphoblasts induced by cytochalasin B and analysis of sister chromatid exchanges. The study included 48 exposed workers and 15 controls. In 16 exposed workers increased incidence of unstable chromosomal aberrations (dicentrics, rings and acentrics) was found, while in 19 no structural chromosomal aberrations could be detected. In 11 workers changes defined as chromosomal and chromatid breaks were noted. This type of change, however, can be evidenced in a non-exposed population as well. In two workers stable chromosomal aberrations were recorded (translocations and inversions). The incidence of micronuclei as well as exchange of sister chromatids were elevated in the exposed group of workers compared to controls.     

Risk of spontaneous abortion among women exposed to polybrominated biphenyls

Accidental contamination of livestock in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. At the time of enrollment, serum was collected and analyzed for PBBs and polychlorinated biphenyls (PCBs). In 1997, women aged 18 years or older and active in the registry were invited to participate in a telephone interview about their health. Using generalized estimating equations to account for correlated outcomes within the same woman, we assessed the risk of spontaneous abortion among 529 women with 1344 potentially exposed pregnancies. PBB and PCB exposure were not associated with risk of spontaneous abortion after adjusting for maternal age at conception, age at menarche, and prior infertility. Compared to pregnancies with PBB exposure below the limit of detection, those with levels above 2.9 ppb had a non-significant reduced odds of spontaneous abortion (adjusted OR=0.73; 95% CI=0.47-1.13). Compared to pregnancies with PCB exposure below the limit of detection, those with levels above 6.5 ppb had little difference in risk (adjusted OR=0.91; 95% CI=0.59-1.41). Maternal age at conception above 34 years was significantly associated with elevated risk of spontaneous abortion (OR=2.46; 95% CI=1.10-5.49). The effect of prior infertility was of borderline significance (OR=1.52; 95% CI=0.98-2.38). Older age at menarche was associated with decreased risk of spontaneous abortion (adjusted OR=0.58; 95% CI: 0.38-0.89, comparing menarche at 12-13 with menarche <12). Our results do not support an association between exposure to PBBs or PCBs and risk of spontaneous abortion.     

Menstrual effects among women exposed to polychlorinated biphenyls and dibenzofurans

Background

Polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs), and dibenzo-dioxins (PCDDs) may affect the female reproductive system in humans. A mass poisoning occurred in Taiwan due to PCBs/PCDFs-contaminated cooking oil, and was called the Yucheng (oil-disease in Chinese). We aimed to determine whether Yucheng women were affected in their menstruation.

Methods

After the event, we followed the exposed individuals and an age-matched neighborhood reference group. Menstrual cycle characteristics and age at menarche were obtained by a telephone interview. We used multiple linear and logistic regression to examine the association between PCBs/PCDFs and menstrual cycle characteristics, after adjusting for confounding factors.

Results

Totally 445 women responded satisfactorily and were included in the analyses of menstrual characteristics. Menstrual cycle irregularity and dysmenorrheal did not differ between Yucheng and referents. Yucheng women's menstrual cycles were 0.5 (95% CI: 0.0–0.5; p=0.03) days shorter than those of the referents. The Yucheng women with skin lesions caused by PCBs/PCDFs were more prominently affected, with the cycles 1.2 days shorter than the referents. Yucheng women exposed to PCBs/PCDFs at the premenacheal period had reduced cycle length (−0.7 day, 95% CI: −1.4 to 0.0; p=0.04) and longer days of menstrual flow (0.5 day, 95% CI: 0.0–1.0; p=0.04). Among those women who were exposed at an age of 5–9 years, menarche started slightly earlier with borderline significance.

Conclusions

Shorter menstrual cycle length and a longer duration of bleeding in each cycle were found among women previously exposed to PCBs/PCDFs. These effects were more obviously observed among those exposed at premenarcheal ages.     

Mortality in male and female capacitor workers exposed to polychlorinated biphenyls

A mortality study was conducted in workers with at least 90 days' exposure to polychlorinated biphenyls (PCBs) between 1946 and 1977. Vital status was established for 98.7% of the 7075 workers studied. In hourly male workers, the mortality from all cancers was significantly below expected (standardized mortality ratio [SMR] = 81; 95% confidence interval [CI], = 68 to 97) and comparable to expected (SMR = 110; 95% CI, 93 to 129) in hourly female workers. No significant elevations in mortality for any site-specific cause were found in the hourly cohort. All-cancer mortality was significantly below expected in salaried males (SMR = 69; 95% CI, 52 to 90) and comparable to expected in salaried females (SMR = 75; 95% CI, 45 to 118). No significant elevations were seen in the most highly exposed workers, nor did SMRs increase with length of cumulative employment and latency. None of the previously reported specific excesses in cancer mortality were seen. This is the largest cohort of male and female workers exposed to PCBs. The lack of any significant elevations in the site-specific cancer mortality of the production workers adds important information about human health effects of PCBs.     

Half-life of polychlorinated biphenyls in occupationally exposed workers

In 1977 and 1985, serum polychlorinated biphenyl (PCB) concentrations were determined for 58 workers in a Bloomington, Indiana, factory that used polychlorinated biphenyls (PCBs) in capacitor manufacture until 1977. Less chlorinated PCBs were quantitated as Aroclor 1242, and more highly chlorinated PCBs were quantitated as Aroclor 1254. The median half-life was 2.6 y for Aroclor 1242 and 4.8 y for Aroclor 1254. However, the half-life varied inversely with the initial serum concentration. This pattern may be a result of continued low-level exposure, variation in the time of exposure, or enzyme induction by PCBs.     

Developmental abilities of children exposed to polybrominated biphenyls (PBB).

To investigate whether ingestion of polybrominated biphenyls has an adverse effect on the neuropsychological development of young children exposed in utero and in infancy, five tests of the McCarthy Scales of Children's Abilities were administered to a group of 19 PBB-exposed Michigan children. When the data for the exposed group were analyzed according to body burden of PBB as determined by fat biopsy, correlations ranging from -.5228 to -.3004 were found between the natural logarithms of the children's fat PBB values and their standardized scores on the developmental scales. Four of the five correlations were significant at p less than .05. Multivariate analysis of covariance confirmed the existence of a significant main effect for fat PBB level, with parental education held constant. Children with higher body burdens of PBB (greater than .100 ppm) scored significantly lower than exposed children with lower body burdens on the same four tests, and on a composite score representing overall performance. These results suggest the existence of an inverse relationship between body levels of PBB and some developmental abilities in young children.     

Reproduction success of American kestrels exposed to dietary polychlorinated biphenyls

While reproduction of wild birds is adversely affected by multiple environmental contaminants, we determined that polychlorinated biphenyls (PCBs) alone alter reproduction. Captive American kestrels (Falco sparverius), fed PCB-spiked (Aroclor 1248:1254:1260) food (7 mg/kg body weight/d) prior to and during the first breeding season only (100 d) laid eggs with environmentally relevant levels of total PCBs (34.0 microg/g whole egg wet wt vs 0 microg/g for controls). Reproduction changed during, not after, PCB exposure in this two-year study. The PCB-exposed pairs laid smaller clutches later in the season and laid more totally infertile clutches. Hatching success was reduced in PCB-exposed pairs, and 50% of PCB nestlings died within 3 d of hatching. Nearly 60% of PCB-exposed pairs with hatchlings failed to produce fledglings. Higher levels of total PCB residues and congeners were associated with later clutch initiation and fewer fertile eggs, hatchlings, and fledglings. We suggest that nonpersistent PCB congeners have a greater influence on reproduction than do persistent congeners.     

Responses of rats exposed to polychlorinated biphenyls for fiftytwo weeks

Male Sprague-Dawley rats consumed a diet to which 100 ppm of various polychlorinated biphenyl (PCB) mixtures (Aroclors^® 1248, 1254, and 1262) were added for one year. Rats were hepatectomized at 13, 26, and 52 weeks during feeding and at 13 weeks following the discontinuation of the PCB diets. The liver homogenates of these rats had an increase in protein and RNA on a DNA basis and an increase in lipid and a decrease in DNA on a liver weight basis. The hepatic microsomes from these livers also had an increase in protein and cytochrome P-450. The RNA/microsomal protein levels were decreased, and no marked alterations were recorded for the phospholipids and cholesterol on a microsomal protein basis. Increased enzymatic activity was recorded for N-demethylase and nitroreductase. However, the specific activity of glucose-6-phosphatase was decreased throughout the treatment period.     

Mortality and industrial hygiene study of workers exposed to polychlorinated biphenyls

Because of the demonstrated toxic effects on animals resulting from exposure to polychlorinated biphenyls (PCBs), the National Institute for Occupational Safety and Health conducted a retrospective cohort mortality study of 2,567 workers in two plants where PCBs were used in the manufacture of electrical capacitors. All workers included in the study were employed for at least 3 months in areas of the plants where PCBs were used. The vital status of 98% of the two cohorts was determined, and 39,018 person-years were accumulated. All-cause mortality was lower than expected (163 obs. vs 182.4 exp.) as well as all cancer mortality (39 obs. vs 43.8 exp.). Excess mortality was noted for rectal cancer (4 obs. vs 1.19 exp.) and liver cancer (3 obs. vs 1.07 exp.), although neither excess was statistically significant. In one of the plants the observed mortality due to cirrhosis of the liver was also elevated. The results of detailed industrial hygiene surveys conducted in each plant are also presented.     

Effects of polychlorinated biphenyls and terphenyls and polybrominated biphenyls on pentobarbital sleeping times of Japanese quail

Polychlorinated biphenyls (Aroclor 1221, 1232, 1242, 1248, 1254, 1260, 1262 and 1268), polychlorinated terphenyls (Aroclor 5460), a mixture of poly chlorinated biphenyls and terphenyls (Aroclor 4465) and polybrominated biphenyls (BP-6) were administered in a single dose, 100 mg/kg body weight injected orally, to mature male and female Japanese quail. Two hr after Aroclor treatment, pentobarbital sleeping times were prolonged (2 to 3 × control) in both male and female quail. Twenty-four hr after treatment, sleeping times were similar to those of controls. However, 48 hr after treatment with Aroclor 1248 through Aroclor 5460 and with BP-6, sleeping times of males were only 1/2 those of controls, whereas after treatment with Aroclor 1221, 1232 and 1242, sleeping times were similar to those of controls. The reduction in sleeping times of male quail 48 hr after administration of PCBs was correlated with the percentage of chlorine in the PCB with greater reductions in male than female quail. The response after three daysad libitum feeding of 300 ppm of each substance was the same as the response 48 hr after a single oral injection. Although very few birds died from the toxicity of the Aroclors and BP-6, mortality was greatly increased during anesthesia when the pentobarbital was administered two hr after single oral dosing.     

Cancer mortality among electric utility workers exposed to polychlorinated biphenyls.

OBJECTIVES: To assess whether excess mortality from cancer, malignant melanoma of the skin, and cancers of the brain and liver in particular, is associated with long term occupational exposure to polychlorinated biphenyls (PCBs). METHODS: An epidemiological study of mortality was conducted among 138,905 men employed for at least six months between 1950 and 1986 at five electrical power companies in the United States. Exposures were assessed by panels composed of workers, hygienists, and managers at each company, who considered tasks performed by workers in 28 job categories and estimated weekly exposures in hours for each job. Poisson regression was used to examine mortality in relation to exposure to electrical insulating fluids containing PCBs, controlling for demographic and occupational factors. RESULTS: Neither all cause nor total cancer mortality was related to cumulative exposure to PCB insulating fluids. Mortality from malignant melanoma increased with exposure; rate ratios (RRs) relative to unexposed men for melanoma were 1.23 (95% confidence interval (95% CI) 0.56 to 2.52), 1.71 (0.68 to 4.28) and 1.93 (0.52 to 7.14) for men with < 2000, > 2000-10,000, and > 10,000 hours of cumulative exposure to PCB insulating fluids, respectively, without consideration of latency. Lagging exposure by 20 years yielded RRs of 1.29 (0.76 to 2.18), 2.56 (1.09 to 5.97), and 4.81 (1.49 to 15.50) for the same exposure levels. Mortality from brain cancer was modestly increased among men with < 2000 hours (RR 1.61, 95% CI 0.86 to 3.01) and > 2000-10,000 hours exposure (RR 1.79, 95% CI 0.81 to 3.95), but there were no deaths from brain cancer among the most highly exposed men. A lag of five years yielded slightly increased RRs. Mortality from liver cancer was not associated with exposure to PCB insulating fluids. CONCLUSIONS: This study was larger and provided more detailed information on exposure than past investigations of workers exposed to PCBs. The results suggest that PCBs cause cancer, with malignant melanoma being of particular concern in this industry.