Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake

Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, "dioxin") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.     

Presence of dioxins in human follicular fluid: their possible stage-specific action on the development of preimplantation mouse embryos

Examination of human follicular fluid revealed the presence of polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) at concentrations of approximately 1 pg/ml (0.01 pg TEQ/ml). To study their possible action, two-cell mouse embryos were cultured in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at concentrations between 0.5 and 100 pM and evaluated at 24-h intervals for their development to the eight-cell and blastocyst stages. The percentage of eight-cell embryos exposed to TCDD at 1, 2, and 5 pM concentrations was significantly lower than that of controls. However, blastocyst formation of the surviving eight-cell embryos was accelerated, with the number of cells in the blastocysts increased in a dose-dependent manner. Findings suggest that PCDDs and PCDFs may be present in human reproductive fluid and may exert some stage-specific effects on early embryonic development.     

Alcohol consumption and risk of breast cancer: a multicentre Italian case-control study

The relationship between alcohol consumption and breast cancer risk was investigated using data from a co-operative case-control study conducted in Italy between 1991 and 1994 on 2569 incident, histologically confirmed breast cancer cases and 2588 controls in hospital for acute, non-neoplastic, non-hormone related conditions. Overall, 915 (38%) cases and 1048 (43%) controls were abstainers. Compared with them, the odds ratio (OR), adjusted only for age, was 1.31 (95% confidence interval (CI) 1.13-1.53) for drinkers and became 1.39 (95% CI 1.(1)21-1.60) after correction for measurement error. The multivariate OR was 1.21 for drinkers of < or = 5.87 g/day and 1.23, 1.19, 1.21, 1.41 for drinkers of 5.88-13.40, 13.41-24.55, 24.56-27.60, > 27.60 g/day, respectively. The trend in risk was significant (chi 2 = 12.28, P < 0.0005). The association was apparently stronger in premenopausal women (OR = 1.80 for > 27.60 g/day). Considering the different types of alcoholic beverages (wine, beer, digestives, grappa and other spirits), a significant direct trend in breast cancer risk was seen for wine with an OR of 1.27 (95% CI 1.06-1.53) for the category > 26.34 g/day. The ORs were also above unity for beer, grappa, digestives and spirits drinkers. No appreciable interaction was observed between alcohol drinking and body mass index, smoking, or any other covariate considered. Thus, the present data, based on a validated alcohol consumption questionnaire and on a population characterised by a relatively high alcohol consumption in women, confirmed that alcohol drinking is moderately related to breast cancer risk. If causal, this association could explain 12% (95% CI, 5-19%) of breast cancers in Italy, thus representing one of the major avoidable risk factor for breast cancer.     

Symbiotic mutants deficient in nodule establishment identified after T-DNA transformation of Lotus japonicus

The concentrations of polychlorinated naphthalenes (PCNs) were determined together with polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), 1,1-bis-(4-chlorophenyl)-2,2,2-trichloroethane (p,p'-DDT), 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) in milk, sampled in the course of 1972-92 from mothers living in Stockholm. A previously developed method for multicomponent analysis of organochlorine environmental contaminants was adapted for simultaneous analysis of PCNs. The mean recoveries of seven chlorinated naphthalene (CN) congeners added to milk prior to extraction were 76-99%. Similar recoveries were obtained for the commercial PCN product Halowax 1014. The pattern of PCNs in milk differed to a great extent from that in the commercial PCN products. The dominating congeners in breast milk were 1,2,3,5,7-pentachloronaphthalene (CN-52), 1,2,3,4,6,7- and/or 1,2,3,5,6,7-hexachloronaphthalene (CN-66/ CN-67) and one unidentified tetrachloronaphthalene. There was a notable decrease in the concentrations of PCNs as was of the other organochlorine contaminants in milk from 1972 to 1992. During this time period the sum of CN congeners decreased from 3,081 to 483 pg/g milk fat and the sum of toxic equivalents of dioxin and dioxin-like compounds decreased from 100 to 39 pg/g milk fat.     

Interactions between 2,3,7,8-TCDD and PCBs as tumor promoters: limitations of TEFs

The assessment of the carcinogenic risk of polychlorinated dioxins (PCDDs), furans (PCDFs), and biphenyls (PCBs) by TEFs is hampered by species- and tissue-specific responses that cannot readily be explained by differences in the Ah receptor levels but may be due to events subsequent to ligand binding to the Ah receptor. Moreover, PCDDs and related compounds accumulate in the environment, in animal and human tissues as highly complex mixtures. Thus, comprehensive risk assessment should include all Ah receptor ligands and agents that modulate the Ah receptor-mediated responses. Tumor promoter studies with mixtures of PCDDs and halogenated biphenyls have shown additive, synergistic, and antagonistic effects. To analyse the interactions of TCDD and PCBs as tumor promoters in more detail, we established an in vitro assay, i.e., the enhancement (promotion) of malignant transformation of carcinogen-initiated C3H/M2 mouse fibroblasts after treatment with tumor promoters. The coplanar PCB 126, a potent Ah receptor agonist, and the diortho-substituted PCB153, to which no TEF value has been ascribed, are promoters of malignant transformation. A defined mixture of PCB126 and TCDD had an additive promoting effect, while PCB 153 antagonized the TCDD-mediated promotion. Thus, the TEF-approach may be insufficient to estimate the tumor-promoting activities of PCDDs, PCDFs, and PCBs in mammalian tissues in which diortho-substituted PCBs are greatly accumulated.     

Polychlorinated diphenyl ethers, dibenzo-p-dioxins, dibenzofurans and biphenyls in seals and sediment from the Gulf of Finland

Polychlorinated diphenyl ethers (PCDEs), 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in seals from the Gulf of Finland and in sediments from the Gulf of Finland and near Gotland. The sediments included one surface core from both sampling sites. The seal material consisted of 14 ringed seals and 6 grey seals that all were found dead and examined for pathology. The main aims were to scrutinize levels and patterns of PCDEs for the first time in seals from the Baltic Sea and to estimate whether chlorinated compounds mentioned have an influence on an exceptional high mortality that occurred among ringed seals in the Gulf of Finland in late 1991. The concentrations of 50 congeners of tetra- through deca-CDEs analyzed ranged from < 0.3 to 62 ng/g lipid weight (lw) in seal blubber, but in the sediments PCDEs were non-detectable (tetra- through hepta-CDEs < 0.1 ng/g dry weight (dw)). In ringed seals with good nutritional status, the concentrations of almost all PCDE congeners were greater in two adult females than in specimens of younger age groups. The concentrations of PCDDs and PCDFs as TCDD-equivalents exceeded those of the coplanar (non-ortho) PCBs in sediments, whereas non- and monoortho PCBs constituted greater toxic loads as those calculated for PCDDs and PCDFs in seals. However, the levels revealed do not explain the high mortality of ringed seals.     

Contaminants in ospreys from the Pacific Northwest: I. Trends and patterns in polychlorinated dibenzo-p-dioxins and -dibenzofurans in eggs and plasma

Osprey (Pandion haliaetus) eggs were collected from 1991 to 1997 at nests (n = 121) upstream and downstream of bleached kraft pulp mills and at reference sites in the Fraser and Columbia River drainage systems of British Columbia, Washington, and Oregon. Blood samples were collected from nestling ospreys during the 1992 breeding season on the Thompson River. Samples were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs) and -dibenzofurans (PCDFs). Mean concentrations of 2,3,7,8-TCDD were significantly higher in eggs collected in 1991 at downstream compared to upstream nests near pulp mills at Kamloops and Castlegar, British Columbia. There were no significant temporal trends in 2,3,7,8-TCDD, -TCDF or other measured compounds at a sample of nests monitored between 1991 and 1994 downstream of the Castlegar pulp mill, despite changes in bleaching technology (CIO2 substitution). However, by 1997 concentrations of 2, 3,7,8-TCDD and -TCDF were significantly lower than previous years in nests sampled downstream at both Castlegar and Kamloops. An unusual pattern of higher chlorinated PCDDs and PCDFs was found in many of the osprey eggs collected in this study, and considerable individual variation in the pattern existed among eggs from the same site. For example, eggs from four different nests at one study area (Quesnel) on the Fraser River had concentrations of 1,2,3,4,6,7,8-HpCDD ranging from <1 to 1,100 ng/kg and OCDD from <1 to 7,000 ng/kg wet weight. Higher mean concentrations of HpCDD and OCDD were found in eggs from the Thompson River, a tributary of the Fraser, compared to the Columbia River, and concentrations were generally higher at nests upstream of pulp mills. In plasma samples, 1,2,3,4,6,7,8-HpCDD and OCDD were the main compounds detected, with no significant differences measured between samples upstream versus downstream or earlier versus later in the breeding season. Use of chlorophenolic wood preservatives by lumber processors was considered the main source of higher chlorinated PCDD/Fs throughout the systems, based on patterns of trace PCDFs in eggs and significant correlations between egg concentrations of pentachlorophenol and both HpCDD (r = 0.891, p < 0.01) and OCDD (r = 0.870, p < 0.01).     

Cocaine and cocaethylene binding to human milk

The relationship between frequency of intake of different types of fat and breast cancer was investigated in a case-control study conducted in Montevideo, Uruguay, during the time period 1994-1996. Our study comprised 365 cases and 397 controls. A moderate and non-significant increase in risk of breast cancer, associated with total fat intake, was found. Saturated and monounsaturated fat intake were not associated to an increased risk of this malignancy, whereas polyunsaturated fat and linoleic acid were associated with a significantly reduced risk (OR 0.26, 95% CI 0.13-0.53). On the contrary, both alpha-linolenic acid and cholesterol intakes were associated with an increased risk of breast cancer (OR for the upper quartile of intake of alpha-linolenic acid 3.79, 95% CI 1.53-9.40). When alpha-linolenic was examined at different levels of intake, the OR's were significantly higher at low levels of linoleic acid intake (OR 7.5, 95% CI 1.9-28.8).     

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in shellfishes from south coast of Korea

PCDDs and PCDFs were analyzed by high resolution GC-MS in two species of shellfish collected from southern coast of Korea. PCDDs and PCDFs were detected from all samples. Total concentration of PCDDs and PCDFs ranged from 4.4 to 19 pg/g wet weight and from 2.5 to 26 pg/g wet weight, respectively. By using a method of cluster analysis based on congener profiles, samples were categorized into two groups, "the urban group" and "the rural group". A tendency that TEQ levels of the urban group were higher than those of the other group was observed. Although a reliable source of dioxins in the samples was identified in this study, it was suggested that combustion sources are responsible for occurrence of dioxins in samples of both groups.     

Polychlorinated diphenyl ethers, dibenzo-P-dioxins and dibenzofurans in Finnish human tissues compared to environmental samples

Finnish human samples from the Helsinki area and Arctic cod samples from Vestertana Fjord (Norway) were analyzed for polychlorinated diphenyl ethers (PCDE) and 2,3,7,8-chloro substituted dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). The PCDE, PCDD and PCDF contents in human and animal samples from Finland and elsewhere were briefly reviewed. PCDEs were non-detectable in human liver and testis, but some PCDE congeners were identified in human adipose tissue and fat of boiled Arctic cod liver composite. The contents of PCDEs in Finnish human samples were similar to those reported in the literature for human tissues from North America. The estimated concentrations of PCDEs 99, 147 + 153 (coeluting) and 206 ranged between 2 and 8 ng/g lipid weight (lw) in one Finnish human adipose tissue. The concentrations of PCDE congeners identified in the cod liver fat were between 0.4 and 5 ng/g lw. Of toxic PCDDs and PCDFs, hepta- and octa-CDDs dominated in human. The concentrations of PCDD and PCDF congeners varied from < 2 to 7700 pg/g lw in human. In Arctic cod samples analyzed (muscle tissues of an air dried cod and cod liver fat), 2,3,7,8-tetra-CDF was nearly the only congener of PCDD/PCDFs detected.     

Evaluation of an immunoturbidimetric assay for haemoglobin A1c on a Cobas Mira S analyser

A case-control study was carried out in Spain to assess associations between parity, lactation and age at first full-term pregnancy and breast cancer. From November 1989 to February 1992, 184 incident breast cancer histologically confirmed cases were interviewed and matched by age and residence to 184 hospitalized patients and 184 community controls selected by random digit dialing. Multiple logistic regression was used to assess the independent influence of each factor on the risk of breast cancer in relation to other factors included in the model. Age at first full-term pregnancy was associated with breast cancer risk with an estimated odds ratio of 3.5 (95% CI 1.41-9.83) for women with their first birth after 30 years in comparison with those whose first birth was before age 21. Breast cancer risk decreased with increasing number of full-term pregnancies, OR 0.3 (95% CI 0.16-0.78) for women who had had more than 3 full-term pregnancies in comparison with nulliparous women. Among parous women, the estimated OR for women with more than 3 children was 0.4 (95% CI 0.13-0.81) after allowance for age at first childbirth and lactation. The estimated OR was 2.6 (95% CI 1.4-4.7) for women with a positive history of breast cancer in first-degree relatives. Breast cancer was not associated with total duration of lactation. The study indicates that parity is an independent risk factor associated to breast cancer and that the women with a late age at first full-term pregnancy constitute a high-risk group.     

Alcohol and breast cancer in the Swiss Canton of Vaud

The relationship between alcoholic beverage drinking and the risk of breast cancer was considered using data from a case-control study of breast cancer conducted between 1990 and 1995 in the Swiss Canton of Vaud on 230 incident cases of breast cancer below age 75 years, linked with the Vaud Cancer Registry, and 507 controls admitted to the same network of hospitals for a wide spectrum of acute, non-neoplastic, non-hormone-related conditions. Overall, 70.4% of cases versus 57.4% of controls consumed alcohol, corresponding to a multivariate odds ratio (OR) of 1.5 (95% confidence interval (CI): 1.1-2.2). The ORs were 1.3 for < 1 drink per day, 1.8 for 1 to 2, 1.5 for 2 to 4, and 2.7 for > 4 drinks per day, and the trend in risk with dose was significant. The association was consistent for wine (OR = 2.0), beer (OR = 2.6) and spirits (OR = 2.0) and was apparently stronger in premenopausal women, whereas no noticeable interaction was observed with any of the hormonal or reproductive risk factors for breast cancer. The alcohol-related risk was unrelated to duration; the OR was 1.8 for women who started drinking below the age of 30 years and 1.4 for those starting at the age of > or = 30 years. Thus, the present study confirms that alcohol is a correlate of breast cancer risk in this European population, where alcohol drinking among women is common and relatively high. Assuming that this association reflects causality, in terms of attributable risk, alcohol could explain 25% (8-42%) of breast cancer cases.     

Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.     

Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies

To examine the effects of smoking and N-acetylation genetics on breast cancer risk, we analyzed data from an ongoing, population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 498 cases and 473 controls, with approximately equal numbers of African-American and white women, and women under the age of 50 and age 50 years or older. Among premenopausal women, there was no association between current smoking [odds ratio (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95% CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also no association with current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1) for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and 0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1) nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased breast cancer risk. There was little evidence for modification of smoking effects according to genotype, except among postmenopausal women. Among postmenopausal women, ORs for smoking within the past 3 years were greater for women with the NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI, 0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast cancer should investigate the effects of environmental tobacco smoke, diet, and other exposures.     

Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants

Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs) on thyroid hormone status were studied in the peripheral blood of 36 breast-fed Japanese infants. Estimated total intakes of these chemicals in toxic equivalent quantity (TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) from the breast milk significantly and negatively correlated with the levels of triiodothyronine (T3) and thyroxine (T4) in the blood of breast-fed babies. Therefore, exposure to background levels of the highly toxic organochlorine chemicals through the breast milk may cause some effects on thyroid hormone status in Japanese infants.     

Breast cancer and heredity: results of a population case-control study in Girona

BACKGROUND: To characterise the relationship between breast cancer and different aspects of the reproductive life, use of drugs and alcohol by family history of breast cancer. PATIENTS AND METHODS: From the cancer registry of Girona, Spain, 330 women were identified with histologically confirmed breast cancer during 1986-1989. For each case, a control woman was selected from a random sample of the population living in the matched area to the case by age (+/- 5 yr.). The information was collected by a personal interview and included: family history of breast cancer, reproductive history, presence of acne during the teenage years, use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol consumption. RESULTS: 18.5% of breast cancer cases and 8.9% of all controls had a family history of breast cancer. Family history on a first degree relative (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than the general population. Women with a first degree family history of breast cancer were at higher risk for breast cancer if they had a history of acne during the teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no family history had a higher breast cancer risk if they had a late menarche, long menstrual periods, late first full term pregnancy, and history of acne during puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders were associated with a decreased risk of breast cancer. CONCLUSIONS: First degree family history of breast cancer seems to be the best risk indicator for developing breast cancer. Long menstrual periods and presence of acne during puberty may indicate hormonal imbalance that act independently of the family history in breast cancer development.     

Symptom-related self-care of Mexican Americans with type 2 diabetes: preliminary findings of the Starr County Diabetes Education Study

OBJECTIVES: Late age at first birth and nulliparity are established risk factors for breast cancer, yet the extent to which fertility problems contribute to these associations remains largely unexplored. Here, we examine self-reported fertility problems as a risk factor for breast cancer in young women. METHODS: We used a population-based case-control study of 2,173 cases and 1,990 controls aged 20 to 54 years in the United States. Structured in-person interviews were used to elicit detailed information on established and potential breast cancer risk factors. Information was collected on pregnancy details, including difficulties becoming pregnant or maintaining a pregnancy. RESULTS: Self-reported difficulty in becoming pregnant or maintaining a pregnancy was reported by 450 cases and 377 controls. Overall, there was little association between these fertility problems and risk of breast cancer (odds ratio [OR] = 1.05). Parity was associated with a decreased risk of breast cancer in women both with (OR = 0.71) and without (OR = 0.79) fertility problems. There was little evidence of an increased risk of breast cancer with later age at first full-term birth among women without fertility problems (ORage 35+ :age <20 = 1.13, 95 percent confidence interval [CI] = 0.7-1.9), but a relatively strong association among women with fertility problems (ORage 35+ :age <20 = 2.96, CI = 1.3-7.0). Among women with a first full-term birth at age 35 or older, fertility problems were associated with a twofold risk of breast cancer. Analyses of duration of unprotected sexual intercourse prior to first pregnancy as an alternative estimate of infertility produced similar results. CONCLUSIONS: Our study suggests that the association between late age at first birth and breast cancer is stronger among women with self-reported fertility problems than among women with no fertility problems.     

The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity

This article reviews the present state of the art regarding the toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). The absorption, body distribution, and metabolism can vary greatly between species and also may depend on the congener and dose. In biota, the 2,3,7,8-substituted PCDDs and PCDFs are almost exclusively retained in all tissue types, preferably liver and fat. This selective tissue retention and bioaccumulation are caused by a reduced rate of biotransformation and subsequent elimination of congeners with chlorine substitution at the 2,3,7, and 8 positions. 2,3,7,8-Substituted PCDDs and PCDFs also have the greatest toxic and biological activity and affinity for the cytosolic arylhydrocarbon (Ah)-receptor protein. The parent compound is the causal agent for Ah-receptor-mediated toxic and biological effects, with metabolism and subsequent elimination of 2,3,7,8- substituted congeners representing a detoxification process. Congener-specific affinity of PCDDs and PCDFs for the Ah-receptor, the genetic events following receptor binding, and toxicokinetics are factors that contribute to the relative in vivo potency of an individual PCDD or PCDF in a given species. Limited human data indicate that marked species differences exist in the toxicokinetics of these compounds. Thus, human risk assessment for PCDDs and PCDFs needs to consider species-, congener-, and dose-specific toxicokinetic data. In addition, exposure to complex mixtures, including PCBs, has the potential to alter the toxicokinetics of individual compounds. These alterations in toxicokinetics may be involved in some of the nonadditive toxic or biological effects that are observed after exposure to mixtures of PCDDs or PCDFs with PCBs.     

Origin attribution of polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment and soil from a Japanese freshwater lake area through congener-specific data analysis

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) in sediment and soil from a freshwater lake area were congener-specifically determined. The obtained data were examined to estimate the major origins of these compounds, with the aid of principal component analysis (PCA). Four major principal components (PCs) were obtained, and three of them were attributed to PCDDs/PCDFs in the atmosphere, in a diphenyl ether herbicide and in pentachlorophenol, based on congener-specific comparisons with references. One PC remained unattributed. These four were interpreted as the major origins of PCDDs/PCDFs in the area. The relative influence of the origins was also investigated.     

History of lactation and breast cancer risk

A self-administered questionnaire was completed by 1,018 women diagnosed with breast cancer during 1988-1989 identified through the British Columbia Cancer Registry and by 1,025 controls selected at random from the Provincial Voters List. Parous premenopausal women who had never nursed (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.9-2.0) or who had lactated for 1 month or less (OR = 1.8, 95% CI 1.3-2.5) had an increased risk of breast cancer adjusted for age and parity, compared with women who had breast-fed 2 months or longer. The risk was particularly elevated (OR = 3.0, 95% CI 1.6-5.4) among women who reported having tried to nurse, but who were unsuccessful. Among women who nursed for at least 2 months, there was an indication of decreasing risk with increasing duration of nursing. Among postmenopausal parous women, no relation between lactation history and breast cancer risk was evident.