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Biomedical subjects

H Becher

Publications and source records attributed to H Becher.

At least 37 records · Page 2Linked to original sources

Elimination of beta-hexachlorocyclohexane in occupationally exposed persons.

The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of beta-HCH. The data support the assumption of first-order kinetics.

Adipose Tissue

Familial aggregation of oesophageal cancer in a high incidence area in China.

BACKGROUND: The high incidence of oesophageal cancer in northern China is attributed predominantly to environmental factors. The role of genetic factors has not been extensively studied. METHODS: Our aim was to study familial aggregation of oesophageal cancer in pedigrees from a defined population base in a high incidence area in China and to quantify the risk associated with different first degree relatives using different analytical approaches. Detailed data on family members of three successive generations and the occurrence of oesophageal and other cancers in family members were collected from a population-based series of 244 oesophageal cancer cases which occurred between 1987 and mid-1992 in Huixian County, Henan. RESULTS: Compared to expected rates, the standardized mortality ratio (SMR) of oesophageal cancer among first degree relatives of oesophageal cancer patients was 2.4 (2.2 in male and 2.7 in female relatives). The corresponding SMR for first and second degree relatives were 1.6 and 2.2. The null hypothesis of 'no familial aggregation' was rejected using Tarone's one-sided score test for binomial distributions indicating some evidence for clustering within families. To account for variance due to between-pairs correlation and family and/or individual specific variables, we fitted a series of regression models using a Generalized Estimation Equations (GEE) approach. The pairwise odds ratios were 2.3 for parent-parent, 1.9 for sib-parent and 1.1 for sib-sib, adjusted for sex, age and sex of index case. DISCUSSION: The existence of familial aggregation of oesophageal cancer in the study population was confirmed using different analyses and a two- to threefold increased risk was found for first degree relatives. The clear association of disease between parent and sib provides some indication of a genetic component. The pairwise association between parents but not between sibs suggests that environmental factors have a stronger action after childhood.

Aged

Association between acute cerebrovascular ischemia and chronic and recurrent infection.

BACKGROUND AND PURPOSE: We performed a case-control study to investigate whether chronic or recurrent respiratory, ear-nose-throat (ENT), and dental infections are risk factors for cerebrovascular ischemia. METHODS: Using a standardized questionnaire we investigated past infectious diseases in 166 consecutive patients with acute cerebrovascular ischemia and in 166 age- and sex-matched nonstroke neurological patient controls. In subgroups, we performed standardized ENT (69 patients, 66 control subjects) and dental examinations including orthopantomography (66 patients, 60 control subjects). Dental status was determined by a total dental index (TDI) that reflects caries, periapical lesions, periodontitis, and other dental lesions and by an orthopantomography index (OPGI) that was assessed blinded. RESULTS: Frequent (> or = 2 episodes in each of the 2 preceding years) or chronic bronchitis was associated with cerebrovascular ischemia in age-adjusted multiple logistic regression analysis (odds ratio, OR, 2.2; 95% confidence interval, CI, 1.04 to 4.6). Groups were not different in ENT examination. Patients tended to have a worse dental status (TDI: P = .070; OPGI: P = .062) and had more severe periodontitis (P = .047) and periapical lesions (P = .027) than control subjects. In age-adjusted multiple logistic regression analysis with social status and established vascular risk factors, poor dental status (TDI) was independently associated with cerebrovascular ischemia (OR, 2.6; 95% CI, 1.18 to 5.7). CONCLUSION: Recurrent or chronic bronchial infection and poor dental status, mainly resulting from chronic dental infection, may be associated with an increased risk for cerebrovascular ischemia.

Acute Disease

Estimating the generalized impact fraction from case-control data.

The generalized impact fraction (also called the generalized attributable fraction) was introduced by Walter (1980, American Journal of Epidemiology 112, 409-416) and Morgenstern and Bursic (1982, Journal of Community Health 7, 292-309) as a measure that generalizes the population attributable fraction (attributable risk). It is defined as the fractional reduction of a disease resulting from changing the current distribution of a risk factor to some modified distribution. We show that the point and variance estimator derived by Greenland and Drescher (1993, Biometrics 49, 865-872) for fixed shift functions can be extended to situations where the shift is a probabilistic function of the actual exposure value. The formulas are applicable for case-control designs where the cases are simply randomly selected and the controls are chosen in one of three ways: simple random sampling, stratified random sampling, and frequency matching.

Alcohol Drinking

A topographic analysis of atrophic gastritis and stomach cancer risk. A clinicoepidemiological study in Poland.

The purpose of this cross-sectional study was to assess the relation between intestinal and diffuse stomach cancer at its various locations with topography of atrophic gastritis. The study population consisted of 3435 patients who reported over the period of 1991-1994 for the first time to gastroenterological outpatient clinics of 7 university medical centers in Poland. Among these subjects there were 131 histologically proved consecutive cases of gastric carcinoma. The reference group consisted of 1540 patients among whom endoscopic examination did not reveal peptic ulcers, polyps, deformations of antrum or bulbus duodenum and mucosa erosions. Gastroscopy on gastric cancer patients and the reference group was performed and biopsy specimens were obtained from the tumour and from the antrum and stomach corpus distant from the tumour. Among the gastric cancer cases there was a higher prevalence of atrophic gastritis in the intestinal than in the diffuse type. The highest prevalence of atrophic gastritis irrespective of its degree and stomach area was observed in the tumour-area of intestinal cancer located distally (78.9%), and the lowest in the tumour-free area in diffuse proximal cancer (18.5%). Prevalence of atrophic pangastritis (atrophic gastritis present both in the corpus and antrum) was also highest in intestinal distal cancer (69.2%) and lowest in diffuse proximal cancer (21.7%). The age-adjusted correlation coefficients between gastritis score in the tumour-area and tumour-free area were highly significant. It was shown that only atrophic pangastritis was significantly associated with gastric cancer irrespective of its histology and location (OR = 3.8, 95% CI:2.4-6.0), however, it was much stronger related to the intestinal gastric cancer (OR = 5.9, 95% CI: 3.1-11.0), than to the diffuse carcinoma (OR = 2.2, 95% CI: 1.1-4.3).

Adult

The association of leukocyte count, fibrinogen and C-reactive protein with vascular risk factors and ischemic vascular diseases.

In 154 subjects (age 63 +/- 11 years; 63 women and 91 men) randomly selected from the population, we tested the hypothesis that inflammatory parameters are associated with vascular risk factors and particularly with a history of ischemic vascular diseases. The subjects were part of the control group (n = 197) in a case-control study investigating recent infection as a risk factor for acute cerebrovascular ischemia and had been matched for sex and age with patients suffering from acute ischemic stroke or transient ischemic attack. Subjects with malignant or inflammatory diseases, with recent trauma, surgery or vascular diseases (n = 43) were excluded from the present analysis. In multivariate analysis, current smoking, diabetes mellitus, age > or = 65 years, and a history of stroke independently increased the leukocyte count. Hypertriglyceridemia, peripheral arterial disease, and diabetes mellitus were positively associated with C -reactive protein (CRP). Age > or = 65 years and diabetes mellitus independently increased fibrinogen. (p < 0.05, respectively) Subjects with a history of cerebrovascular, cardiovascular or peripheral arterial disease had higher leukocyte counts, fibrinogen and CRP than subjects without vascular risk factors and higher leukocytes and fibrinogen than subjects with one or more risk factors. Subjects under the age of 65 with vascular risk factors but without ischemic diseases had higher leukocyte count, fibrinogen and CRP and subjects older than 65 with risk factors had higher CRP than subjects without risk factors or ischemic diseases in the same age group. (p < 0.05, respectively) These results support the hypotheses that low-grade inflammation is associated with vascular risk factors and that inflammatory mechanisms may contribute to the risk of organ ischemia.

Adolescent

Estimating disease risks for individuals with a given family history in different populations with an application to breast cancer.

For many chronic diseases, including most of the common cancers, a family history is known to be a strong independent risk factor. For breast cancer, estimation of risk as a function of family history is considered to provide useful risk assessment for women with a family history of breast cancer. Detailed tables that predict the cumulative risk of breast cancer at specific ages based on various combinations of family history have been constructed for the American white population. Most chronic diseases, however, have a multiple etiology, with multiple genetic and environmental factors. Family history can thus be a result of different susceptibility loci and the aggregation of sporadic cases by chance. Since the relative contribution of the genetic factor may differ in different populations, these tables may not be directly applicable to other populations. We present a method to decompose available estimates of risk based on family history for an arbitrary disease into probabilities for genotype frequency given a particular family history and for disease probabilities by genotype carrier status. These can be reconstructed to obtain risk estimates for different populations. Implicit assumptions are made in the estimation process. These are based on the current state of knowledge and can be updated as further knowledge accumulates.

Adult

Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.

In an occupational cohort study, the relation between exposure to phenoxy herbicides, and contaminants (dioxins and furans) and cancer mortality was investigated. A total of 2,479 workers from four plants in Germany were included, with a mortality follow-up until the end of 1989 (for one cohort, until the end of 1992). A total of 484 deaths were recorded yielding a standardized mortality ratio (SMR) of 101 (95 percent confidence interval [CI] = 92-111) for total mortality, and an SMR of 119 (CI = 100-141) for all malignant diseases. A variety of herbicides was produced, including those which are known to have been contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). High dioxin and furan exposure (in particular, exposure to TCDD, but also to higher chlorinated dioxins) had occurred in two of the four plants as shown by blood-fat measurements in a sample of workers. Mortality from all neoplasms increased with latency and was highest in the largest plant where the highest TCDD blood levels were recorded. An increased mortality in the total cohort from respiratory cancer (SMR = 154, CI = 115-202), cancer of the buccal cavity and pharynx (SMR = 295, CI = 135-560), and non-Hodgkin's lymphoma (SMR = 326, CI = 119-710) was observed. Our findings are consistent with results from other cohorts which showed an increased overall cancer mortality and mortality of respiratory cancer after long-term exposure to these phenoxy herbicides and dioxins.

Adipose Tissue

Elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in occupationally exposed persons.

The elimination of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was investigated in a group of n = 43 exposed workers with 2 blood measurements and n = 5 workers with 3 measurements. Under the assumption of a one-compartment, first-order kinetic model the median half-life for 2,3,7,8-TCDD was 7.2 yr, while for the other dioxins the estimates were between 3.7 yr for 1,2,3,4,6,7,8-HpCDD (hepta-chlorinated) and 15.7 yr for 1,2,3,7,8-PCDD (penta-chlorinated). For the furans median half-lives between 3.0 yr for 1,2,3,4,6,7,8-HpCDF and 19.6 yr for 2,3,4,7,8-PCDF were observed. There was no indication for a deviation from a first-order kinetic. Increasing age and percent body fat were associated with increasing half-life for most of the congeners. Smokers in general had a faster decay than non- and ex-smokers. In summary, the higher chlorinated PCDD/F like TCDD appear to be highly persistent in humans with half-lives ranging between 4 and 12 yr.

Adipose Tissue

German family study on hereditary breast-ovarian cancer.

An estimated 5% to 10% of all breast and ovarian cancers are attributed to dominant susceptibility genes. Two such genes, BRCA1 and BRCA2, were recently identified. The involvement of these genes was studied in 43 German breast only and breast-ovarian cancer families. All families contained three or more cases of breast or ovarian cancer, with at least two diagnosed under the age of 60 years. Multipoint linkage analysis gave a maximum lod score of 2.13 at the BRCA1 locus under the assumption of genetic heterogeneity, with an estimated 50% of families being linked. Among the 33 breast only cancer and 10 breast-ovarian cancer families, the estimated proportions of linked families were 35% and 75%, respectively. Sixteen families with at least four cases of female breast cancer diagnosed under the age of 60 years, or male breast cancer diagnosed at any age, were analysed for linkage to BRCA2. Positive lod scores at BRCA2 were obtained in six families.

Adult

[Controlled clinical studies for topographic analysis of atrophic gastritis and stomach cancer].

The purpose of this cross-sectional study was to assess the relation between intestinal and diffuse stomach cancer at its various locations with topography of atrophic gastritis. The study population consisted of 3435 patients who reported over the period of 1991-94 for the first time to gastroenterological outpatient clinics of 7 university medical centers in Poland. Among these subjects there were 131 histologically proved consecutive cases of gastric carcinoma. The reference group consisted of 1540 patients among whom endoscopic examination did not reveal peptic ulcers, polyps, deformations of antrum or bulbus duodenum and mucosa erosions. Among the gastric cancer cases there was a higher prevalence of atrophic gastritis in the intestinal than in the diffuse type. The highest prevalence of atrophic gastritis irrespective of its degree and stomach area was observed in the tumour-area of intestinal cancer located distally (78.9%), and the lowest in the tumour-free area in diffuse proximal cancer (18.5%). Prevalence of atrophic pangastritis (atrophic gastritis present both in the corpus and antrum) was also highest in intestinal distal cancer (69.2%) and lowest in diffuse proximal cancer (21.7%). For other types of cancer the prevalence rates of atrophic pangastritis was 50.0% in intestinal proximal cancer and 37.5% in diffuse distal carcinoma. The age-adjusted correlation coefficients between gastritis score in the tumour-area and tumour-free area were highly significant. It was shown that only atrophic pangastritis was significantly associated with gastric cancer irrespective of its histology and location (OR = 3.8, 95% CI:2.4-6.0), however, it was much stronger related to the intestinal gastric cancer panga (OR = 5.9, 95% CI: 3.1-11.0), than to the diffuse carcinoma (OR = 2.2, 95% CI: 1.1-4.3).

Adult

Clinical evaluation of left heart Doppler contrast enhancement by a saccharide-based transpulmonary contrast agent. The Levovist Cardiac Working Group.

OBJECTIVES: A multicenter study was carried out to evaluate the efficacy with which SHU 508A enhances left heart Doppler signals and improves the clinical quantification of valve disease. BACKGROUND: Poor signal-to-noise ratio often limits the Doppler interrogation of left heart flows. This problem may be resolved by the enhancement of Doppler signals by an ultrasound contrast agent capable of pulmonary transmission, such as the recently developed SHU 508A. METHODS: Left heart contrast enhancement was tested for 1) continuous wave Doppler evaluation in 51 patients with aortic stenosis, 2) pulsed Doppler transthoracic evaluation of pulmonary venous flow in 85 patients, and 3) color Doppler evaluation of mitral regurgitation in 60 patients. Studies were performed immediately before and during the intravenous administration of SHU 508A (16 ml of 200 mg/ml) and compared with unenhanced transesophageal data in representative subsets of patients. RESULTS: SHU 508A had no serious adverse effects. A significant increase in left heart Doppler signal intensity lasted for 30 to 300 s. The continuous wave Doppler velocity envelope was enhanced for all jets, but Doppler peak velocity was not altered in high quality baseline studies. However, Doppler contrast enhancement resulted in higher measured peak gradients (p < 0.001) in 29 patients with aortic stenosis who had poor quality baseline studies. This improved the overall correlation with invasive pressure measurements (r = 0.73 vs. r = 0.89, p < 0.01). The enhanced pulsed Doppler traces of transthoracic pulmonary venous flow allowed quantitative analysis in 92% patients (vs. 27% at baseline) and correlated well with peak velocities and velocity profiles obtained by transesophageal echocardiography (r = 0.91, p < 0.001). The enhanced color Doppler display of regurgitant jets increased jet area with a high interindividual variability (mean 276%), resulting in almost identical jet areas as unenhanced transesophageal values (r = 0.97, p < 0.001). CONCLUSIONS: SHU 508A is a safe transpulmonary contrast agent that significantly enhances both spectral and color Doppler signals in the left heart. In specific patient subsets, the increase in signal-to-noise ratio improved the quantitative assessment of aortic stenosis, pulmonary venous flow and mitral regurgitation.

Aortic Valve Stenosis

Lung cancer deaths attributable to indoor radon exposure in West Germany.

BACKGROUND: There is substantial epidemiological and experimental evidence that exposure to radon at levels found in underground mines can cause lung cancer. Although radon levels measured in homes are normally substantially lower, there is concern about the presence of a known lung carcinogen in a residential setting. METHODS: Using national survey data on radon concentrations in homes in the former West Germany, the proportion and absolute numbers of lung cancer deaths attributable to radon are estimated. As lung cancer risk models derived directly from residential radon studies are not yet available, the risk model developed recently by Lubin et al. from a joint analysis of 11 underground miners' studies is applied. For an estimate of the impact of smoking on radon-attributable lung cancers, three different approaches are used and compared. RESULTS: Our analysis shows that after adjusting for dosimetry differences between mines and homes about 7% of all lung cancer deaths in the western part of Germany may be due to residential radon. This corresponds to a total of about 2000 deaths (95% CI: 500-8200), 400 in females and 1600 in males. Adjusting for the intermediate relationship for smoking and radon, the attributable risk is estimated to be about 4-7% for smokers and 14-22% in non-smokers. CONCLUSIONS: Our analysis basically confirms the results of former calculations with regard to the total number of lung cancer deaths attributable to radon in West Germany. However, we show that the standard practice that applies the same model to smokers and non-smokers may result in biased estimates for these groups.

Air Pollution, Indoor

Recent infection as a risk factor for cerebrovascular ischemia.

BACKGROUND AND PURPOSE: Previous infection is discussed as a risk factor for ischemic stroke in children and younger adults. We tested the hypothesis that the role of recent infection in cerebrovascular ischemia is not restricted to younger patients and investigated which infections are mainly relevant in this respect. METHODS: We performed a case-control study with 197 patients aged 18 to 80 years with acute cerebrovascular ischemia and 197 randomly selected control subjects matched for sex, age, and area of residence. RESULTS: Infection within 1 week before ictus or examination was significantly more common among patients (38 of 197) than control subjects (10 of 197; odds ratio [OR], 4.5; 95% confidence interval [CI], 2.1 to 9.7). Patients more often had febrile and subfebrile infections (> or = 37.5 degrees C) than control subjects (29 of 197 versus 5 of 197; OR, 7.0; 95% CI, 2.5 to 20). Respiratory tract infections were most common in both groups. Bacterial infections dominated among patients but not among control subjects. Infection increased the risk for cerebrovascular ischemia in all age groups; this reached significance for patients aged 51 to 60 and 61 to 70 years. The profile of vascular risk factors was similar in patients with and patients without previous infection. Infection remained a significant risk factor when previous stroke, hypertension, diabetes mellitus, coronary heart disease, and current smoking were included as covariates in a logistic model (OR, 4.6; 95% CI, 1.9 to 11.3). CONCLUSIONS: Recent infection, primarily of bacterial origin, may be a risk factor for cerebrovascular ischemia in older as well as younger patients.

Adolescent

Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies.

We examined the effect of exposure to chemicals present in the production and spraying of phenoxy herbicides or chlorophenols in two nested case-control studies of soft tissue sarcoma and non-Hodgkin's lymphoma. Eleven sarcoma and 32 lymphoma cases occurring within an international cohort were matched for age, sex, and country of residence with 55 and 158 controls, respectively. Exposures to 21 chemicals or mixtures were estimated by three industrial hygienists who were blind to the subject's case-control status. Excess risk of soft tissue sarcoma was associated with exposure to any phenoxy herbicide [odds ratio (OR) = 10.3; 95% confidence interval (CI) = 1.2-91] and to each of the three major classes of phenoxy herbicides (2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, and 4-chloro-2-methylphenoxyacetic acid), to any polychlorinated dibenzodioxin or furan (OR = 5.6; 95% CI = 1.1-28), and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (OR = 5.2; 95% CI = 0.85-32). Sarcoma risk was not associated with exposure to raw materials or other process chemicals. In the non-Hodgkin's lymphoma study, associations were generally weaker than those found in the study on sarcoma. These findings indicate that workers exposed to phenoxy herbicides and their contaminants are at a higher risk of soft tissue sarcoma.

Case-Control Studies

[Risk assessment for familial occurrence of breast cancer].

There is now unequivocal evidence that an estimated 5% of breast cancer cases is inherited in families. Inherited predisposition of cancer in these families is thought to be the result of a mutation in one of several highly penetrant autosomal dominant genes such as BRCA1 or BRCA2. The BRCA1 gene which is localized on chromosome 17 q was recently isolated and at about the same time BRCA2 was localized to chromosome 13 q. A number of other genetic mutations is also associated with predisposition to breast cancer but accounts for a very small proportion of inherited breast cancer. Many women want to know whether they have inherited a gene predisposing to breast cancer. Those with a family history of breast cancer are particularly concerned about their risk of disease. Currently the assessment of an individual's risk of breast cancer can be undertaken using prediction models based on family history and can be further refined when molecular genetic investigations became available. Without molecular characterisation the Claus tables derived from the Cancer and Steroid Hormone Study data set are best suited to predict breast cancer risk based on age of onset of affected relatives. Direct screening for mutations in breast cancer genes in not yet generally available. Testing for inherited susceptibility is currently being offered to selected families where multiple cases of breast and/or ovarian cancer are diagnosed at an early age (younger than 45 years) as part of research protocols. In these families the so-called indirect gene analysis for linkage of disease to BRCA1 and BRCA2 or the direct analysis of mutations with functional significance in the BRCA1 gene allows relatively refined risk assessment for non-diseased female family members. Some examples will be presented to illustrate risk assessment in different familial and individual situations. Risk assessment including test result interpretation and counselling can be appropriately provided directly to the patient by physicians and genetic counsellors in a coordinated genetic counselling setting.

Adult

[Occupational exposure and histologic differentiation of lung cancer. Retrospective assessment in Cracow].

A population-based case-control study was performed in Cracow, Poland. Male cases and controls were identified from the Cracow Death Register. Information were obtained by mailed questionnaire from next-of-kin on smoking, occupational branch, occupational exposures and other pertinent variables. Response rates were 73.5% in cases and 72.0% in controls. For cases that underwent a bronchial biopsy or surgical excision the histological diagnosis of the tumor was obtained from clinical records. The case group contained 343 subjects with squamous cell carcinomas, 151 small cell carcinomas and 106 adenocarcinomas. 27 cases showed other histological types (large cell carcinoma and not classifiable). Analysis was performed separately by histological type for occupational exposure variables adjusted for smoking. Long-term exposure to mineral dust and metal dust (20 years or more) was found to be a significant risk factor for small cell and squamous cell carcinoma. The effect was more pronounced if the analysis was restricted to the age groups "less than 70 years". The highest relative risk due to occupational exposures was found for squamous cell carcinoma and mineral dust exposure for more than 20 years (RR = 2.45, 95% CI 1.43-4.19). The estimated effect of mineral dust on small cell carcinoma and adenocarcinoma was slightly lower (RR = 2.29, 95% CI 1.16-4.53 and RR = 2.04, 95% CI 0.89-4.64, respectively). The effect of metal dust and fumes appeared to be about the same for squamous and small cell carcinoma.

Adenocarcinoma

[Epidemiological risk assessment for chemical substances].

Epidemiological risk assessment for chemicals is usually based on analytical studies like case-control or cohort studies. Both study types have a number of specific advantages and disadvantages which are outlined. The evaluation of a substance is done on the basis of the results of these studies either qualitatively or quantitatively. For quantitative risk assessment reliable data are needed for the dose of the substance to which the individuals in the study were exposed. For a number of chemical sufficient data are available. Among these are experimental pollutants like arsenic, benzene or radon. As an example the possibilities of risk assessment for dioxin are outlined. The knowledge on the carcinogenicity of dioxin has significantly improved during the last years. Some research groups currently use data of a number of cohort studies to perform a quantitative risk assessment.

Carcinogens