Showing papers by "Vincent Cogliano published in 2006"

Carcinogenicity of carbon black, titanium dioxide, and talc

Abstract: In February, 2006, 19 scientists from eight countries met at the International Agency for Research on Cancer (IARC), Lyon, France, to reassess the carcinogenicity of carbon black, titanium dioxide, and non-asbestiform talc. These assessments will be published as volume 93 of the IARC Monographs, and are the fi rst assessments since the IARC Monograph preamble was amended. All three of the above agents are poorly soluble particles that are weakly toxic, and were chosen for assessment because evidence suggests that they cause cancer in the respiratory tract of rats through similar mechanisms: after exposure to high concentrations of these agents, deposition of particles onto the respiratory epithelium can lead to enhanced particle retention, impaired lung clearance, infl ammatory response, production of reactive oxygen species, cell injury, cell proliferation, fi brosis, induction of mutations, and, ultimately, cancer. Because many of these steps arise in people who work in dusty environments (eg, coal miners), data on cancer in animals obtained in conditions of impaired lung clearance could be relevant to human beings. Furthermore, impaired lung clearance and adverse eff ects in the lungs of rats that have been exposed to ultrafi ne particles (<100 nm) occur at much lower mass concentrations than in rats exposed to fi ne particles (<10 μm), increasing the potential relevance to human beings. Carbon black is a particulate form of elemental carbon. About 90% of carbon black is used in rubber products, mainly tyres. Carbon black is also used as a pigment in inks, paints and coatings, and in plastics. Exposure to carbon-black particles occurs mainly in the form of aggregates (ie, particle size, 50−600 nm) and agglomerates (227 μm). Most types of carbon black have small quantities (ie, <1%) of organic compounds, including polycyclic aromatic hydrocarbons, adsorbed onto their surface. The highest exposures to carbon black arise during its manufacturing. Exposure in industries that use carbon black is diffi cult to assess because data are scarce. No substantial exposure to carbon black is thought to occur when it is bound to other materials such as rubber, printing ink, or paint. Workers who produced carbon black in Germany and the UK had an excess risk of lung cancer. Confounding by smoking was unlikely to explain the entire excess risk, but no clear dose-response relation between exposure to carbon black and lung cancer was noted. A US study of workers in carbon black production found no excess risk of lung cancer, but no data according to level of exposure were reported. A study of workers in the rubber industry in Germany who were exposed to carbon black showed no signifi cant excess risk of lung cancer after adjustment for potential confounding by asbestos and talc. The working group concluded that the epidemiological studies of carbon black provided inadequate evidence of carcinogenicity. Carbon black and its extracts have been tested in rats and mice by inhalation, intratracheal instillation, dermal application, and subcutaneous injection. The overall results provided suffi cient evidence in laboratory animals for the carcinogenicity of carbon black and carbon-black extracts. The working group classifi ed carbon black as possibly carcinogenic to human beings (ie, group 2B). Titanium dioxide accounts for 70% of the total production volume of pigments worldwide. The primary particles are typically 200–300 nm in diameter, but larger aggregates and agglomerates are formed readily. Ultrafi ne grades of titanium dioxide (ie, 10–50 nm) are used in sunscreens and plastics to block ultraviolet light, and in catalysts. Highest expo sures occur in titanium-dioxide produc tion during packing, milling, site cleaning, and maintenance. Exposure data for industries that use titanium dioxide are scarce. The largest epidemiological cohort study considered included workers in the titanium dioxide production industry in six European countries, and showed a small but signifi cant increase in risk of lung cancer compared with that for the general population; however, the data did not suggest an exposure-response relation. Two cohort studies undertaken in the USA did not report excess risks of lung cancer, neither did a Canadian population-based casecontrol study. Overall, the working group concluded that the epidemiological studies on titanium dioxide provide inadequate evidence of carcinogenicity. Pigment-grade titanium dioxide and ultrafi ne titanium dioxide have been tested in rats, mice, and hamsters by various routes of administration. Overall, results from studies of inhalation and intratracheal instillation provided suffi cient evidence in animals for the carcinogenicity of titanium dioxide. The working group classifi ed titanium dioxide as possibly carcinogenic to human beings (ie, group 2B). Talc refers to both mineral talc and industrial products that contain 35% to >95% mineral talc. Mineral talc Upcoming meetings

Carcinogenicity of nitrate, nitrite, and cyanobacterial peptide toxins

Abstract: In June, 2006, 19 scientists from eight countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to assess the carcinogenicity of ingested nitrate and nitrite, and the cyanobacterial peptide toxins microcystin-LR and nodularins. These agents are linked environmentally through the runoff of agricultural fertilisers that increase nitrogen concentrations in surface water and groundwater, and that could contribute to cyanobacterial growth in surface water. The assessments will be published as volume 94 of the IARC Monographs. Nitrate and nitrite are naturallyoccurring ions. In the past century, the global nitrogen cycle has been increasingly aff ected by nitrogen fi xation for agricultural activities, which now exceeds the amount that occurs naturally. Both groundwater and surface water can be contaminated by excess nitrate as a result of agricultural activities. Human exposure to nitrate and nitrite is mainly from the ingestion of food. Important sources include vegetables, cereal products, and cured meat. Drinking-water is generally not the main source of nitrate, unless concentrations exceed the WHO guideline of 50 mg/L, which is especially found in contaminated groundwater. Ingested nitrate (NO3) is excreted in the saliva and reduced to nitrite (NO 2) mainly by oral bacteria. Under acidic conditions in the stomach, nitrite then reacts readily with nitrosatable compounds, especially sec ondary amines and alkyl amides, to generate N-nitroso compounds. Several N-nitroso compounds are potential human carcinogens. The nitrosation reactions can be inhibited by the presence of vitamin C or other antioxidants. Some epidemiological studies assessed the risk of cancer in people who had high intake of nitrite or nitrate and low intake of vitamin C, a dietary pattern that could result in increased endogenous formation of N-nitroso compounds. The Working Group weighted these studies more heavily than studies without this information. From the epidemiological studies of nitrate in food, no increased risk of cancer was seen. For nitrate in drinkingwater, epidemiological studies were few, exposure levels were low, and endogenous nitrosation was not often considered. For ingested nitrite, the risk for stomach cancer was investigated in seven well-designed case-control studies. Six of these showed consistent, positive associations, four of which were signifi cant. Two studies looked at eff ect modifi cation, and the risk was most pronounced in people who had high nitrite and low vitamin C intake. Neither of the two cohort studies reported a clear positive association. No study accounted for potential confounding or eff ect modifi cation by Helicobacter pylori, an important risk factor for stomach cancer. For oesophageal cancer, two well-designed case-control studies investigated an association with nitrite intake. Both reported a positive association for nitrite intake overall; for people with high nitrite and low vitamin C intake, these associations were signifi cant. For brain tumours, two of fi ve casecontrol studies in children showed positive associations with nitrite intake. In one study, children born to mothers with the highest intake of nitrite from cured meat during pregnancy had a three-fold increased risk for brain tumours. The other study reported an increased risk for astroglial brain tumours in the children of mothers whose drinking-water had high nitrite concentrations. For adult brain cancer, no clear pattern emerged from seven case-control studies. The Working Group concluded that there is “limited evidence of carcinogenicity” for nitrite in food based on the association with stomach cancer. For nitrate in food and nitrate or nitrite in drinking-water, the studies provide “inadequate evidence of carcinogenicity”. No increased incidence of tumours was recorded in mice and rats if nitrate alone was added to the drinking-water or to the diet, providing inadequate evidence of carcinogenicity. Mice given nitrite in drinking-water showed a signifi cant trend in the incidence of forestomach papillomas and carcinomas combined. Rats exposed to nitrite in utero and throughout life had an increased incidence of lymphoreticular tumours, and mice with similar exposure had raised incidences of lymphoma and lung tumours. These results provide limited evidence of carcinogenicity for nitrite alone. Many studies of mice and rats tested nitrite in combination with specifi c secondary or tertiary amines or amides, added to the diet or drinkingwater, or by gastric intubation. Most combinations resulted in increased incidences of benign and malignant tumours at many organ sites. The Working Group concluded that these results provided “suffi cient evidence of carcinogenicity” for nitrite in combination with amines or amides. The combination of positive and negative results from epidemiological Upcoming meetings

Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide

Abstract: Members Mario Altamirano-Lozano, Unidad de Investigación en Genética y Toxicología Ambiental (UNIGEN), Facultad de Estudios Superiores-Zaragoza, Battalla del 5 de mayo esq. Fuerte de Loreto Col. Ejercito de Oriente, C.P. 09230 Mexico, DF, Mexico Detmar Beyersmann, Department of Biology & Chemistry, Fachbereich 2, University of Bremen, Leobener Strasse NW2, Raum B2230, 28359 Bremen, Germany (Chairman) Dean E. Carter, Department of Pharmacology & Toxicology, Center for Toxicology, College of Pharmacy, University of Arizona, 1703 E. Mabel, Tucson, AZ 85721, USA (unable to attend) Bruce A. Fowler, Senior Research Advisor, ATSDR/CDC, 1600 Clifton Road NE, MS E-29, Atlanta, GA 30333, USA (Subgroup Chair: Other Relevant Data) Bice Fubini, Department of Inorganic, Physical & Material Chemistry and Interdepartmental Center ‘G. Scansetti’ for Studies on Asbestos and other Toxic Particulates, Facoltà di Farmacia, Università degli Studi di Torino, Via P. Giuria 7, 10125 Torino, Italy Janet Kielhorn, Fraunhofer Institute of Toxicology & Experimental Medicine, Department of Chemical Risk Assessment, Nikolai-Fuchs-Strasse 1, 30625 Hannover, Germany Micheline Kirsch-Volders, Laboratorium voor Cellulaire Genetica, Faculteit Wetenschappen, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium Jan Kucera, Nuclear Physics Institute, 250 68 Rez near Prague, Czech Republic Yukinori Kusaka, Department of Environmental Health, School of Medicine, Fukui Medical University, Matsuoka-cho, Fukui 910-1193, Japan (Subgroup Chair: Exposure Data) Gerard Lasfargues, Médecine et Santé au Travail, Faculté de Médecine, 2 bis Bd Tonnelé, B.P. 3223, 37325 Tours Cedex, France Dominique Lison, Industrial Toxicology & Occupational Medicine Unit, Catholic University of Louvain, Clos Chapelle-aux-Champs 30, 1200 Brussels, Belgium IARC WORKING GROUP ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS: COBALT IN HARD METALS AND COBALT SULFATE, GALLIUM ARSENIDE, INDIUM PHOSPHIDE AND VANADIUM PENTOXIDE

Carcinogenicity of household solid fuel combustion and of high-temperature frying

Abstract: In October, 2006, 19 scientists from eight countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to assess the carcinogenicity of household solid fuel combustion (coal and biomass) and of high-temperature frying. These assessments will be published as volume 95 of the IARC Monographs. About half of the world’s population, mostly in low-resource and mediumresource coun tries, use solid fuels for cooking or heating, often in poorly ventilated spaces. WHO identifi ed in door smoke from combustion of solid fuels as one of the top ten risks for worldwide burden of disease. Products of incomplete combustion contain respirable (coarse, fi ne, and ultrafi ne) particles and many volatile and nonvolatile organic compounds, including carcinogens such as benzo[a]pyrene, formaldehyde, and benzene. Average indoor concen trations of particulate matter (<10 μm) can be as high as several milligrams per cubic metre, with peak concentrations an order of magnitude higher. Women and young children who are at home for most of the day are most highly exposed. Although occupational exposure to the combustion products of coal by inhalation is known to cause lung cancer, many studies, mostly from China, now show similar eff ects from household use of coal. The problem was fi rst noted in the county of Xuan Wei, China, where the type of coal used produces especially smoky emissions. Two case–control studies from Xuan Wei reported a positive exposure– response relationship between the amount of coal used and the risk of lung cancer. Subsequently, a cohort intervention study showed transition to the use of a stove with a chimney from one without reduced this risk. A large study in Shenyang, China, noted positive exposure–response associations for diff erent measures of exposure to coal smoke—including a cumulative index of indoor exposure— after adjust ing for smoking and education. Furthermore, a study of non-smoking women in Harbin, China, reported a strong exposure–response relationship between years of use of a coal stove and lung cancer. Case– control studies from Taiwan and the USA have also reported a twofoldincreased risk for lung cancer as a result of coal-smoke inhalation after adjusting for potential confounders. In experiments with animals, inhalation of emissions from coal, burned under conditions similar to those in Xuan Wei, increased the incidence of various types of malignant lung tumours in male and female Kunming mice and of squamous-cell carcinomas in male and female Wistar rats. In another study, the incidence of adenocarcinoma of the lung was increased in male and female Kunming mice exposed to combustion emissions of coal obtained from Harbin. On the basis of suffi cient evidence in both humans and experimental animals, the Working Group concluded that indoor emissions from household combustion of coal are “carcinogenic to humans (Group 1)”. Mechanistic data from studies of humans and animals are consistent with this conclusion. Biomass fuel is much more widely used than coal but the adverse health eff ects have been studied less. In Taiwan, women who burned wood for cooking had a threefold increase in the risk of lung cancer after adjusting for potential confounders. Additionally, a large multicentre European case– control study recorded an adjusted 20–30% increased risk of lung cancer in people who burned wood but not coal, compared with people who never used coal or wood for cooking or heating. Studies in Japan and Mexico also found an increased risk of lung cancer in non-smoking women, which was related to their exposure to smoke from wood or straw. These studies suggest that exposure to smoke from wood combustion is associated with an increased risk of lung cancer; however, the results on exposure duration and intensity are diffi cult to interpret. In animal experiments, exposure to emissions from wood, burned under conditions similar to those in Xuan Wei, increased the incidence of lung adenocarcinomas in male and female Kunming mice, but not in Wistar rats. Extracts from wood smoke, applied to the skin or given subcutaneously, produced cancer in mice and rats. Combustion emissions from wood are mutagenic because of the presence of compounds from various chemical classes, including polycyclic aromatic hydrocarbons and acidic or polar substances. Molecular data, which include changes in expression and phosphorylation of P53 in patients with lung cancer who were exposed to wood smoke, and systemic genotoxicity in charcoal workers and in women who burn cow dung or wood, supports evidence of carcinogenicity of emissions from burning wood. On the basis of limited evidence of carcinogenicity of biomass combustion emissions (mainly from wood) in humans and experimental animals; suffi cient evidence of carcino genicity of wood-smoke extracts in experimental animals; and strong evidence of mutagenicity, Upcoming meetings

Formaldehyde and glutaraldehyde and nasal cytotoxicity: case study within the context of the 2006 IPCS Human Framework for the Analysis of a cancer mode of action for humans.

Abstract: Formaldehyde and glutaraldehyde cause toxicity to the nasal epithelium of rats and mice upon inhalation. In addition, formaldehyde above certain concentrations induces dose-related increases in nasal tumors in rats and mice, but glutaraldehyde does not. Using the 2006 IPCS human framework for the analysis of cancer mode of action (MOA), an MOA for formaldehyde was formulated and its relevance was tested against the properties of the noncarcinogenic glutaraldehyde. These compounds produce similar patterns of response in histopathology and in genotoxicity tests (although formaldehyde has been much more extensively tested studied). The MOA is based on the induction of sustained cytotoxicity and reparative cell proliferation induced by formaldehyde at concentrations that also induce nasal tumors upon long-term exposure. Data on dose dependency and temporal relationships of key events are consistent with this MOA. While a genotoxic MOA can never be ruled out for a compound that is clearly genotoxic, at least in vitro, the nongenotoxic properties fundamental to the proposed MOA can explain the neoplastic response in the nose and may be more informative than genotoxicity in risk assessment. It is not yet fully explained why glutaraldehyde remains noncarcinogenic upon inhalation, but its greater inherent toxicity may be a key factor. The dual aldehyde functions in glutaraldehyde are likely to produce damage resulting in fewer kinetic possibilities (particularly for proteins involved in differentiation control) and lower potential for repair (nucleic acids) than would be the case for formaldehyde. While there have been few studies of possible glutaraldehyde-associated cancer, the evidence that formaldehyde is a human carcinogen is strong for nasopharyngeal cancers, although less so for sinonasal cancers. This apparent discrepancy could be due in part to the classification of human nasal tumors with tumors of the sinuses, which would receive much less exposure to inhaled formaldehyde. Evaluation of the human relevance of the proposed MOA of formaldehyde in rodents is restricted by human data limitations, although the key events are plausible. It is clear that the human relevance of the formaldehyde MOA in rodents cannot be excluded on either kinetic or dynamic grounds.

Use of carcinogenicity bioassays in the IARC monographs.

Abstract: Carcinogenicity bioassays generally provide the best means of assessing the potential for a chemical to be a human carcinogenic hazard. The results of carcinogenicity bioassays are usually the key determinants of IARC Monograph evaluations. Along with carcinogenicity bioassays and epidemiological studies, the International Agency for Research on Cancer (IARC) also encourages the consideration of mechanistic data and other relevant data. During 2005 IARC is updating the Preamble to the IARC Monographs, which describes the principles and procedures used in developing the Monographs, including the criteria that guide the evaluations. Proposed revisions to the Preamble make some changes in the criteria for evaluating carcinogenicity in experimental animals to reflect the greater confidence that can be placed in Good Laboratory Practice (GLP) studies. Other changes will give more specific guidance for the evaluation of mechanistic data. Sections on mechanistic data will be given more prominence in future Monographs and will be more closely linked with toxicokinetics. Future Monographs will also include a new section on susceptible individuals, populations, and life stages that will often be based on the understanding of mechanisms. In addition, the draft Preamble discusses IARC's procedures for promoting impartial evaluations by avoiding conflicts of interests and ensuring that working groups are free from interference.

Butadiene or styrene or butadiene and styrene or else

Abstract: Commentary on the paper by Sathiakumar et al ( Occup Environ Med , December 2005)* In the December 2005 issue of this journal, Sathiakumar and colleagues1 report on the extended follow up of the University of Alabama cohort in the styrene–butadiene–rubber industry. The update confirms the increased risk of haemato-lymphopoietic malignancies in work areas with high exposure to butadiene and styrene. This study is both potentially informative and at the centre of controversies regarding the evidence for the human carcinogenicity of butadiene and styrene. In 1999, an IARC Working Group concluded that butadiene is “probably carcinogenic to humans” (Group 2A) on the basis of “limited evidence” of carcinogenicity in humans and “sufficient evidence” in experimental animals.2 A case-control study nested in the University of Alabama cohort3 showed a consistent excess of leukaemia and a statistically significant dose–response relationship with cumulative exposure to 1,3-butadiene, which remained after adjustment for exposure to styrene. Studies among workers in butadiene production reported an excess of lymphohaematopoietic cancers. In 2002 a separate IARC Working Group concluded that styrene is “possibly carcinogenic to humans” (Group 2B) on the basis …