Exposure to nitrosatable drugs during pregnancy and childhood cancer: A matched case-control study in Denmark, 1996-2016.

BACKGROUND: Nitrosatable drugs can be synthesized to N-nitroso compounds in human stomach. In a pregnant woman, N-nitroso compounds can be translocated to the fetus through the placenta. Maternal exposure of nitrosatable compounds during pregnancy has been associated with childhood brain tumors and leukemia. However, few studies have investigated an association between nitrosatable drug exposure during pregnancy and childhood cancer. We examined if maternal prescriptions of nitrosatable drugs received during pregnancy are associated with childhood cancer. METHODS: A matched case-control study was conducted using Danish nationwide registry data from 1995 to 2016. Each childhood cancer case was matched with twenty-five controls. Maternal exposure of nitrosatable drugs during pregnancy was identified from the Danish National Prescription Register. A multivariable conditional logistic regression model was used to estimate adjusted odds ratios (adj.OR) with 95% confidence intervals (CI) for each childhood cancer type. RESULTS: Maternal prescriptions of nitrosatable drugs positively associate with central nervous system tumors (adj.OR = 1.25; 95% CI = 1.04-1.51) and neuroblastoma (adj.OR = 1.96; 95% CI = 1.34-2.85) in offspring. We also observed a positive association between perinatal exposure of nitrosatable drugs and acute lymphoblastic leukemia (adj.OR = 1.31; 95% CI = 1.07-1.59), however, it appeared to be due to confounding by indication, i.e., maternal infections. CONCLUSION: Nitrosatable drug use during pregnancy potentially increased risk of central nervous system tumors and neuroblastoma. While a positive association between maternal prescriptions of nitrosatable drugs and acute lymphoblastic leukemia should be interpreted cautiously because of confounding by indication.

Replacement of Nitrite in Meat Products by Natural Bioactive Compounds Results in Reduced Exposure to N-Nitroso Compounds: The PHYTOME Project.

SCOPE: It has been proposed that endogenously form N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, the impact of replacing the additive sodium nitrite (E250) by botanical extracts in the PHYTOME project is evaluated. METHOD AND RESULTS: A human dietary intervention study is conducted in which healthy subjects consume 300 g of meat for 2 weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affects molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E250 by natural plant extracts. CONCLUSION: These findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically support by gene expression analyses.

Dietary N-Nitroso Compounds and Risk of Hepatocellular Carcinoma: A USA-Based Study.

BACKGROUND AND AIMS: N-nitroso compounds (NOCs) are among the most potent dietary carcinogens. N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosopiperidine (NPIP) are abundant in foods and carcinogenic to the liver. We investigated the relationship between dietary NOCs and HCC risk. APPROACH AND RESULTS: In this large, hospital-based, case-control study of 827 pathologically or radiologically confirmed HCC cases and 1,013 controls, NOC intake was calculated by linking food frequency questionnaire-derived dietary data with a comprehensive NOC concentration database. Multivariable-adjusted ORs and 95% CIs of HCC by quartiles of NOC consumption were estimated using logistic regression models, with the lowest quartile as the referent. We further investigated joint effects of consuming the highest quartile of NOCs that were associated with increased HCC risk and hepatitis, diabetes, or alcohol drinking on HCC risk. After adjustment for confounding factors, higher intake of NDEA from plant sources (ORQ4 vs. Q1  = 1.58; 95% CI = 1.03-2.41), NDMA from plant sources (ORQ4 vs. Q1  = 1.54; 95% CI = 1.01-2.34), and NPIP (ORQ4 vs. Q1  = 2.52; 95% CI = 1.62-3.94) was associated with increased HCC risk. No association was observed for nitrate or total NOC intake and HCC risk. Higher consumption of HCC-inducing NOCs and positive hepatitis virus status jointly increased the risk of developing HCC. CONCLUSIONS: In conclusion, though some of our findings may indicate the presence of reverse causation owing to lower meat intake among cases with chronic liver diseases before HCC diagnosis, the potent dietary HCC carcinogens, NDEA, NDMA, and NPIP, and their enhanced carcinogenic effects among chronic carriers of hepatitis virus warrant further prospective investigation.

Estimation of nizatidine gastric nitrosatability and product toxicity via an integrated approach combining HILIC, in silico toxicology, and molecular docking.

The liability of the H2-receptor antagonist nizatidine (NZ) to nitrosation in simulated gastric juice (SGJ) and under WHO-suggested conditions was investigated for the first time. For monitoring the nitrosatability of NZ, a hydrophilic interaction liquid chromatography (HILIC) method was optimized and validated according to FDA guidance. A Cosmosil HILIC® column and a mobile phase composed of acetonitrile: 0.04 M acetate buffer pH 6.0 (92:8, v/v) were used for the separation of NZ and its N-nitroso derivative (NZ-NO) within 6 min with LODs of 0.02 and 0.1 µg/mL, respectively. NZ was found highly susceptible to nitrosation in SGJ reaching 100% nitrosation in 10 min, while only 18% nitrosation was observed after 160 min under the WHO-suggested conditions. The chemical structure of NZ-NO was clarified by ESI+/MS. In silico toxicology study confirmed the mutagenicity and toxicity of NZ-NO. Experiments evidenced that ascorbic acid strongly suppresses the nitrosation of NZ suggesting their co-administration for protection from potential risks. In addition, the impacts of the HILIC method on safety, health, and environment were favorably evaluated by three green analytical chemistry metrics and it was proved that, unlike the popular impression, HILIC methods could be green to the environment.

Dietary N-nitroso compounds and risk of pancreatic cancer: results from a large case-control study.

N-nitroso compounds (NOCs) are among the most potent dietary and pancreatic carcinogens. N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) are the most prevalent NOCs identified in foods. Using a validated and comprehensive N-nitroso database developed to estimate total NOCs and important individual NOCs from food intake, we investigated dietary exposure to NOCs in relation to pancreatic cancer in a large matched case-control study. Self-administered food frequency questionnaires were collected from 957 pathologically confirmed pancreatic ductal adenocarcinoma cases and 938 frequency-matched controls. For each food item, frequency of intake and portion size in grams was multiplied by the estimated NOC concentration from the N-nitroso database. Multiple unconditional logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for pancreatic cancer risk by quartiles of NOCs and major food group contributors to NOCs, with the lowest quartile as referent. Following adjustment for confounders, we observed significant positive associations for NDEA (ORQ4 versus Q1 = 2.28, 95% CI = 1.71-3.04, Ptrend < 0.0001) and NDMA from plant sources (ORQ4 versus Q1 = 1.93, 95% CI = 1.42-2.61, Ptrend < 0.0001) with pancreatic cancer. The major food groups related to NDEA and NDMA intakes in this population were fermented cheese, pizza, grains, seafood and beer. No associations of intake of nitrate or total NOCs were observed; nitrite was inversely associated with pancreatic cancer. Although some of our findings probably reflect reverse causation bias due to lower meat intake in cases with latent disease, biologically plausible findings for pancreatic carcinogens, NDEA and NDMA, warrant further prospective investigation.

Effect of diet and gut environment on the gastrointestinal formation of N-nitroso compounds: A review.

Diet is associated with the development of cancer in the gastrointestinal (GI) tract, because dietary nitrate and nitrite are the main nitrosating agents that are responsible for the formation of carcinogenic N-nitroso compounds (NOCs) when nitrosatable substrates, such as amine and amide, are present in the GI tract. However, whether the nitroso compounds become beneficial S-nitroso compounds or carcinogenic NOCs might depend on dietary and environmental factors including food stuffs, gastric acidity, microbial flora, and the mean transit time of digesta. This review focused on GI NOC formation and environmental risk factors affecting its formation to provide appropriate nutritional strategies to prevent the development of GI cancer.

A critical overview on the biological and molecular features of red and processed meat in colorectal carcinogenesis.

A recent investigation by the World Health Organisation (WHO) has found that the consumption of processed meat and potentially red meat promotes carcinogenesis and can increase the risk of colorectal cancer. This literature review aims to summarise both the red and processed meat molecules associated with colorectal carcinogenesis and investigate their relationship with the pathogenic process of colorectal cancer. Literature relating to the carcinogenic effect of red and processed meat molecules was critically reviewed. There are multiple molecules present in red and processed meat with a potential carcinogenic effect on colorectal tissues. Processed meat is more carcinogenic compared to red meat because of the abundance of potent nitrosyl-heme molecules that form N-nitroso compounds. Studies have also noted that other molecules such as polycyclic aromatic hydrocarbons and heterocyclic amines have potential mechanisms for the initiation of colorectal cancer pathogenesis. The non-human sugar molecule N-glycolylneuraminic acid may account for the carcinogenic effects of pork despite its heme content being comparable to that of chicken. Red meat products, especially those that have been processed, have a wide variety of carcinogenic molecules known to increase the risk of colorectal cancer. Thus, the outcome of this review is consistent with the recent findings of WHO.

Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.

Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

Nitrate and nitrite in the diet: how to assess their benefit and risk for human health.

Nitrate is a natural constituent of the human diet and an approved food additive. It can be partially converted to nitrogen monoxide, which induces vasodilation and thereby decreases blood pressure. This effect is associated with a reduced risk regarding cardiovascular disease, myocardial infarction, and stroke. Moreover, dietary nitrate has been associated with beneficial effects in patients with gastric ulcer, renal failure, or metabolic syndrome. Recent studies indicate that such beneficial health effects due to dietary nitrate may be achievable at intake levels resulting from the daily consumption of nitrate-rich vegetables. N-nitroso compounds are endogenously formed in humans. However, their relevance for human health has not been adequately explored up to now. Nitrate and nitrite are per se not carcinogenic, but under conditions that result in endogenous nitrosation, it cannot be excluded that ingested nitrate and nitrite may lead to an increased cancer risk and may probably be carcinogenic to humans. In this review, the known beneficial and detrimental health effects related to dietary nitrate/nitrite intake are described and the identified gaps in knowledge as well as the research needs required to perform a reliable benefit/risk assessment in terms of long-term human health consequences due to dietary nitrate/nitrite intake are presented.

Dietary exposure to meat-related carcinogenic substances: is there a way to estimate the risk?

N-Nitroso compounds (NOCs), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PHAs) are examples of carcinogenic substances, which are formed during cooking and processing of meat. Many researches suggest that high consumption of meat is positively associated with increased risk of some cancers. The majority of the researches are of epidemiological nature and, therefore, provide only associations related to population exposure to diet-related carcinogenic substances. The individual's exposure risk may be estimated by using food frequency questionnaire and analytical methods. However, there is a lack of methods which enable estimation of the risk concerning particular meat meals. The purpose of this paper was to summarize and emphasize the importance of factors influencing the formation of carcinogenic substances in meat during cooking.

Dietary N-nitroso compounds and risk of colorectal cancer: a case-control study in Newfoundland and Labrador and Ontario, Canada.

Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.

Dietary sources of N-nitroso compounds and bladder cancer risk: findings from the Los Angeles bladder cancer study.

N-Nitroso compounds (NOCs) have been proposed as possible bladder carcinogens. The main sources of exogenous exposure to NOCs are cigarette smoke and diet, particularly processed (i.e., nitrite-treated) meats. Perhaps more importantly, NOCs can be formed endogenously from dietary precursors such as nitrate, nitrite and amines. Heme has been shown to increase endogenous nitrosation. We examined the role of dietary sources of NOCs and NOC precursors as potential bladder cancer risk factors using data from the Los Angeles Bladder Cancer Study, a population-based case-control study. Dietary and demographic information was collected from 1,660 bladder cancer cases and 1,586 controls via a structured questionnaire. Intake of liver and of salami/pastrami/corned beef, were both statistically significantly associated with risk of bladder cancer in this study, particularly among nonsmokers. Heme intake was also statistically significantly associated with risk of bladder cancer among nonsmokers only. When considering NOC precursors, risk was consistently higher among subjects with concurrent high intake of nitrate and high intake of the different meats (sources of amines and nitrosamines). Results of this study are consistent with a role of dietary sources of NOC precursors from processed meats in bladder cancer risk, suggesting consumption of meats with high amine and heme content such as salami and liver as a risk factor for bladder cancer. In addition, any effect of consuming these meats may be greater when accompanied by high nitrate intake.

Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study.

Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer.

Adverse effects of preserved vegetables on squamous cell carcinoma of esophagus and precancer lesions in a high risk area.

INTRODUCTION: Squamous cell carcinoma of esophagus (ESCC) is one of the most common cancers in China. Preserved vegetables are processed foods, consumed in high amounts in the high risk areas for ESCC. This study aimed to investigate the relationships of preserved vegetable consumption with SCC and precancer lesions. METHODS: Cases from Yanting cancer hospital with pathological diagnosis of primary cancer, along with controls and individuals diagnosed with precancer lesions by endoscopy with iodine staining were interviewed. Trained staff collected data on dietary habits 1 year before the interview. An unconditional logistic regression model was used to estimate the risk odds ratios for preserved vegetable consumption with precancer lesions and cancer. RESULTS: Adjusting for potential confounders, intake of preserved vegetables (OR=2.92, 95%CI 1.32~6.47) and longer intake period (OR=5.78, 95%CI 2.26~14.80) were associated with higher risk of cancer. Compared with lowest intake frequency, the highest was associated with a 3.0-fold risk for precancer lesions and 3.59-fold risk for ESCC (both p<0.05). CONCLUSION: Consumption of preserved vegetables is a risk factor for esophageal lesions in high risk areas. The carcinogenicity of preserved vegetables needs investigation in further studies and public health strategies for reduction of consumption might be initiated in high risk areas.

Childhood brain tumors and maternal cured meat consumption in pregnancy: differential effect by glutathione S-transferases.

BACKGROUND: Some epidemiologic studies suggest that maternal consumption of cured meat during pregnancy may increase risk of brain tumors in offspring. We explored whether this possible association was modified by fetal genetic polymorphisms in genes coding for glutathione S-transferases (GSTs) that may inactivate nitroso compounds. METHODS: We assessed six GST variants: GSTM1 null, GSTT1 null, GSTP1(I105V) (rs1695), GSTP1(A114V) (rs1138272), GSTM3*B (3-bp deletion), and GSTM3(A-63C) (rs1332018) within a population-based case-control study with data on maternal prenatal cured meat consumption (202 cases and 286 controls born in California or Washington, 1978-1990). RESULTS: Risk of childhood brain tumor increased with increasing cured meat intake by the mother during pregnancy among children without GSTT1 [OR = 1.29; 95% confidence interval (95% CI), 1.07-1.57 for each increase in the frequency of consumption per week] or with potentially reduced GSTM3 (any -63C allele; OR = 1.14; 95% CI, 1.03-1.26), whereas no increased risk was observed among those with GSTT1 or presumably normal GSTM3 levels (interaction P = 0.01 for each). CONCLUSIONS: Fetal ability to deactivate nitrosoureas may modify the association between childhood brain tumors and maternal prenatal consumption of cured meats. IMPACT: These results support the hypothesis that maternal avoidance during pregnancy of sources of some nitroso compounds or their precursors may reduce risk of brain tumors in some children.

Maternal periconceptional consumption of pickled vegetables and risk of neural tube defects in offspring.

BACKGROUND: Maternal exposure to nitrate, nitrite, and N-nitroso compounds from drinking water or diet has been associated with an increased risk of neural tube defects (NTDs) in some studies. Pickled vegetables contain relatively large amounts of nitrite and N-nitroso compounds. We examined the association between maternal periconceptional consumption of pickled vegetables and NTDs in Shanxi Province of northern China. METHODS: Data were derived from a population based case-control study of major external birth defects in four counties of Shanxi Province. Participants included 519 NTDs cases identified between 2003 and 2007 and 694 healthy controls. Exposure information was collected within 1 week after delivery. Multivariable non-conditional Logistic regression model was used to estimate the adjusted odds ratio (OR) controlling for potential confounding variables. RESULTS: The risk of NTDs was positively associated with the frequency of the consumption of pickled vegetables by the mother. Compared with pickled vegetables consumption at < 1 meal/week, the adjusted OR for consumption at 1 - 3, 4 - 6, and > 6 meals/week were 1.3 (95% confidence interval (CI): 1.0, 1.8), 1.9 (1.1, 3.2), and 3.6 (1.9, 6.9), respectively. A protective effect was found for maternal meat consumption at ≥ 1 meal/week (adjusted OR: 0.6, 95%CI: 0.4, 0.7) and egg or milk consumption at ≥ 1 meal/week (adjusted OR: 0.6, 95%CI: 0.4, 0.8). CONCLUSION: Maternal periconceptional consumption of pickled vegetables may increase the risk for NTDs in Shanxi Province.

Dinâmicas de trânsito e degradação da fibra em detergente neutro em bovinos alimentados com forragem tropical de baixa qualidade e compostos nitrogenados / Transit and degradation dynamics of neutral detergent fiber in cattle fed low-quality tropical forage and nitrogenous compounds

Avaliaram-se as dinâmicas de trânsito e degradação da fibra em detergente neutro (FDN) em bovinos alimentados com forragem tropical de baixa qualidade e compostos nitrogenados. Foram utilizadas cinco novilhas Holandês x Zebu fistuladas no rúmen. A alimentação volumosa basal dos animais foi constituída por feno de capim-braquiária (Brachiaria decumbens Stapf.), com 5,08 por cento de proteína bruta (PB), com base na matéria seca (MS), fornecido ad libitum. Os cinco tratamentos avaliados foram definidos de acordo com o nível de suplementação proteica (0, 3, 5, 7 e 9 pontos percentuais acima do nível de PB da forragem). Como fonte de compostos nitrogenados, empregou-se mistura de ureia:sulfato de amônia:albumina (4,5:0,5:1,0). O experimento foi estruturado segundo delineamento em quadrado latino 5 x 5. Os níveis médios de PB nas dietas foram de 5,28; 8,08; 9,82; 11,87 e 13,63 por cento, com base na MS. Verificou-se elevação linear (P<0,05) da fração potencialmente degradável da FDN até o nível de 8,62 por cento de PB, com platô estimado de 47,92 por cento da FDN. Verificou-se efeito quadrático (P<0,05) sobre a taxa de degradação da fração potencialmente degradável da FDN em função dos níveis de PB da dieta, com máxima resposta estimada sobre 13,39 por cento de PB. O fluxo ruminal de partículas fibrosas apresentou relação linear-response-plateau em função do nível de PB na dieta (P<0,05), com ponto crítico para o início do platô sobre 7,59 por cento de PB.

Rumen transit and degradation dynamics of neutral detergent fiber (NDF) in cattle fed low-quality tropical forage and nitrogenous compounds were evaluated. Five crossbred heifers fitted with rumen cannulae were used. The animals were fed ad libitum with signal grass (Brachiaria decumbens Stapf.) hay, which had crude protein (CP) content of 5.08 percent in dry matter (DM). The five treatments were defined according to the level of CP in the diet (0, 3, 5, 7, and 9 percentile points above the CP level of the roughage). The supplement was a mixture of urea, ammonium sulfate, and albumin (4.5:0.5:1.0, respectively). The experiment was carried out according to a 5 x 5 Latin square design. The average CP levels in the diets were: 5.28, 8.08, 9.82, 11.87, and 13.63 percent in DM basis. The potentially degradable fraction of NDF was linearly increased (P<0.05) by CP levels in diet until 8.62 percent CP. From this point, there was stabilization of estimates (47.92 percent of NDF). The degradation rate of potentially degradable NDF showed a quadratic response (P<0.05) to CP levels, with maximal response at 13.39 percent of CP. The ruminal rate of passage of fibrous particles showed a linear-response-plateau (P<0.05) according to CP levels in the diet, with plateau beginning at 7.59 percent of CP.

Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology.

This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the four most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types.