The negative effects of hazardous substances and possible measures that can be taken are evaluated in the environmental risk analysis process, consisting of risk assessment, risk communication and risk management. Uncertainty due to lack of knowledge and natural variability are always present in this process. The aim of this thesis is to evaluate some tools as well as discuss the management of uncertainty and variability, as it is necessary to treat them both in a reliable and transparent way to gain regulatory acceptance in decision making. The catalytic effects of various metals on the formation of chlorinated aromatic compounds during the heating of fly ash were investigated (paper I). Copper showed a positive catalytic effect, while cobalt, chromium and vanadium showed a catalytic effect for degradation. Knowledge of the catalytic effects may facilitate the choice and design of combustion processes to decrease emissions, but it also provides valuable information to identify and characterize the hazard. Exposure factors of importance in risk assessment (physiological parameters, time use factors and food consumption) were collected and evaluated (paper II). Interindividual variability was characterized by mean, standard deviation, skewness, kurtosis and multiple percentiles, while uncertainty in these parameters was estimated with confidence intervals. How these statistical parameters can be applied was shown in two exposure assessments (papers III and IV). Probability bounds analysis was used as a probabilistic approach, which enables separate propagation of uncertainty and variability even in cases where the availability of data is limited. In paper III it was determined that the exposure cannot be expected to cause any negative health effects for recreational users of a public bathing place. Paper IV concluded that the uncertainty interval in the estimated exposure increased when accounting for possible changes in climate-sensitive model variables. Risk managers often need to rely on precaution and an increased uncertainty may therefore have implications for risk management decisions. Paper V focuses on risk management and a questionnaire was sent to employees at all Swedish County Administrative Boards working with contaminated land. It was concluded that the gender, age and work experience of the employees, as well as the funding source of the risk assessment, all have an impact on the reviewing of risk assessments. Gender was the most significant factor, and it also affected the perception of knowledge. / Negativa effekter orsakade av skadliga ämnen och möjliga åtgärder bedöms och utvärderas i en miljöriskanalys, som kan delas i riskbedömning, riskkommunikation och riskhantering. Osäkerhet som beror på kunskapsbrist samt naturlig variabilitet finns alltid närvarande i denna process. Syftet med avhandlingen är att utvärdera några tillvägagångssätt samt diskutera hur osäkerhet och variabilitet hanteras då det är nödvändigt att båda hanteras trovärdigt och transparent för att riskbedömningen ska vara användbar för beslutsfattande. Metallers katalytiska effekt på bildning av klorerade aromatiska ämnen under upphettning av flygaska undersöktes (artikel I). Koppar visade en positiv katalytisk effekt medan kobolt, krom och vanadin istället katalyserade nedbrytningen. Kunskap om katalytisk potential för bildning av skadliga ämnen är viktigt vid val och design av förbränningsprocesser för att minska utsläppen, men det är också ett exempel på hur en fara kan identifieras och karaktäriseras. Information om exponeringsfaktorer som är viktiga i riskbedömning (fysiologiska parametrar, tidsanvändning och livsmedelskonsumtion) samlades in och analyserades (artikel II). Interindividuell variabilitet karaktäriserades av medel, standardavvikelse, skevhet, kurtosis (toppighet) och multipla percentiler medan osäkerhet i dessa parametrar skattades med konfidensintervall. Hur dessa statistiska parametrar kan tillämpas i exponeringsbedömningar visas i artikel III och IV. Probability bounds analysis användes som probabilistisk metod, vilket gör det möjligt att separera osäkerhet och variabilitet i bedömningen även när tillgången på data är begränsad. Exponeringsbedömningen i artikel III visade att vid nu rådande föroreningshalter i sediment i en badsjö så medför inte bad någon hälsofara. I artikel IV visades att osäkerhetsintervallet i den skattade exponeringen ökar när hänsyn tas till förändringar i klimatkänsliga modellvariabler. Riskhanterare måste ta hänsyn till försiktighetsprincipen och en ökad osäkerhet kan därmed få konsekvenser för riskhanteringsbesluten. Artikel V fokuserar på riskhantering och en enkät skickades till alla anställda som arbetar med förorenad mark på länsstyrelserna i Sverige. Det konstaterades att anställdas kön, ålder och erfarenhet har en inverkan på granskningsprocessen av riskbedömningar. Kön var den mest signifikanta variabeln, vilken också påverkade perceptionen av kunskap. Skillnader i de anställdas svar kunde också ses beroende på om riskbedömningen finansierades av statliga bidrag eller av en ansvarig verksamhetsutövare.

First Nations peoples experience many benefits from eating locally-harvested wild foods, but these benefits must be considered along with the potential risks associated with exposure to environmental contaminants. Unlike store-bought foods, wild foods are an important traditional resource and a significant source of dietary protein, essential minerals and polyunsaturated fatty acids, believed to help in the prevention and treatment of obesity and obesity-related diseases such as type-2 diabetes mellitus. Wild foods continue to be an important and healthy food choice for First Nations peoples; however, they are also a primary source of dietary mercury, polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs). To assess the effects of wild food consumption on dietary markers and contaminant accumulation, we grouped individuals from two remote Oji-Cree First Nations communities of north-western Ontario (n=71) according to their level of wild food consumption. In this study, I observed significantly higher organic contaminants in blood and higher mercury concentrations in hair for individuals consuming greater amounts of wild food. Age-adjusted contaminant concentrations were on average 3.5-times higher among high-frequency wild food consumers, with many exceeding federal and international health guidelines for mercury and PCB exposures. Contaminants in these populations approach, and in some cases exceed, threshold levels for adverse effects with potential consequences especially for prenatal development. Here, I also investigated the potential for stable isotope ratios of carbon and nitrogen (δ13C and δ15N) to serve as dietary markers and found strong positive correlations between stable isotopes and frequency of wild food and fish consumption. Frequency of fish consumption and δ15N was also shown to be positively correlated with mercury concentrations in hair and PCB concentrations in plasma. The results of this thesis demonstrate that known differences in dietary behaviour are clearly reflected in stable isotope ratios and contaminant concentrations. The data also show that contaminant exposures to those consuming wild foods in remote Boreal ecosystems is comparable to those associated with serious health effects in industrialized areas, and the problem of contaminants in wild foods is more widespread than the available literature would have led us to believe. These results affect our appreciation of contaminant exposures to First Nations peoples and will have implications for dietary choices, particularly if individuals are encouraged to consume greater amounts of wild foods for their proposed health benefits. We recommend further attention be given to the risks of contaminants in locally-harvested wild foods when promoting the benefits of their consumption to First Nations people as the problem of contaminants in remote communities practicing traditional lifestyles is often underreported and underplayed.

Parkinson’s disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study’s results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.

Parkinson’s disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study’s results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.

Les Hydrocarbures Aromatiques Polycycliques (HAP) sont responsables de cancers du poumon, de la vessie et de la peau. Parmi eux, seul le benzo(a)pyrène (BaP) est classé cancérogène certain pour l'homme. La surveillance biologique de leur exposition passe par le dosage du 1-hydroxypyrène urinaire (1-OHP), métabolite du pyrène non cancérogène. L'objectif de cette thèse était de développer un nouveau biomarqueur plus proche du risque cancérogène. Le 3-hydroxybenzo(a)pyrène (3-OHBaP) est apparu comme le meilleur candidat car c'est le métabolite majoritaire du BaP, car ses concentrations sont liées aux taux d'adduits à l'ADN mesurés dans le poumon de rat et car son dosage est réalisable dans les urines de sujets exposés. Nous avons développé une méthode analytique de routine associant l'extraction en phase solide à la chromatographie liquide avec une détection en fluorescence, qui nous a permis d'atteindre une limite de détection 0,02 ng/L. La médiane des concentrations de 3-OHBaP dans les urines de sujets fumeurs atteignait 0,02 nmole/mole de créatinine et était deux fois plus élevée que chez les non-fumeurs. Dans les secteurs de production du silicium, des cathodes et des anodes, de 30 à 70% des niveaux étaient supérieurs à la valeur recommandée en France, ce qui confirme le risque sanitaire lié à ces activités professionnelles. Lors d'une exposition répétée aux HAP pendant une semaine de travail, le prélèvement des urines doit être réalisé en fin de semaine fin de poste, du fait de l'atteinte d'un équilibre entre les doses de BaP absorbées et celles de 3-OHBaP éliminées. La corrélation entre les niveaux urinaires de 3-OHBaP et de 1-OHP est variable en fonction du secteur et des activités professionnelles. Ceci démontre la difficulté d'établir une seule valeur limite professionnelle en lien avec le risque cancérogène des HAP pour le 1-OHP et souligne tout l'intérêt de doser le 3-OHBaP. / Polycyclic Aromatic Hydrocarbons (PAH) are responsible for lung, skin and bladder cancers. Among them, only benzo(a)pyrene (BaP) is classified as carcinogenic to humans. Their biomonitoring is performed by the determination of urinary 1-hydroxypyrene (1-OHP), a metabolite of the non-carcinogenic pyrene. The aim of this thesis was to develop a new biomarker closest carcinogenic risk. The 3-hydroxybenzo(a)pyrene (3-OHBaP) seemed to be the best candidate because it is the major metabolite of BaP, these urinary levels are related to the rate of DNA adducts measured in the lung of rats and its analysis is achievable in the urine of exposed subjects. We have developed a simple analytical method combining solid phase extraction and liquid chromatography with fluorescence detection, which achieved a detection limit of 0.02 ng/L. The median concentrations of 3-OHBaP in the urine of smokers reached 0.02 nmol/mol of creatinine and was two times higher than among non-smokers. In the industries of silicon, cathodes and anodes, from 30 to 70 % of levels were above the recommended value in France, which confirms the health risk associated with these occupational activities. In case of repeated exposure to PAH during a workweek, urine sampling should be performed at the end of the shift the last workday, due to a balance between the amounts of BaP absorbed and those of 3-OHBaP eliminated. The correlation between urinary levels of 3-OHBaP and 1-OHP is variable depending on the sector and occupational activities. This demonstrates the difficulty of establishing a single limit value in connection with the carcinogenic risk of PAH for 1-OHP and highlights the interest of the 3-OHBaP.

First Nations peoples experience many benefits from eating locally-harvested wild foods, but these benefits must be considered along with the potential risks associated with exposure to environmental contaminants. Unlike store-bought foods, wild foods are an important traditional resource and a significant source of dietary protein, essential minerals and polyunsaturated fatty acids, believed to help in the prevention and treatment of obesity and obesity-related diseases such as type-2 diabetes mellitus. Wild foods continue to be an important and healthy food choice for First Nations peoples; however, they are also a primary source of dietary mercury, polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs). To assess the effects of wild food consumption on dietary markers and contaminant accumulation, we grouped individuals from two remote Oji-Cree First Nations communities of north-western Ontario (n=71) according to their level of wild food consumption. In this study, I observed significantly higher organic contaminants in blood and higher mercury concentrations in hair for individuals consuming greater amounts of wild food. Age-adjusted contaminant concentrations were on average 3.5-times higher among high-frequency wild food consumers, with many exceeding federal and international health guidelines for mercury and PCB exposures. Contaminants in these populations approach, and in some cases exceed, threshold levels for adverse effects with potential consequences especially for prenatal development. Here, I also investigated the potential for stable isotope ratios of carbon and nitrogen (δ13C and δ15N) to serve as dietary markers and found strong positive correlations between stable isotopes and frequency of wild food and fish consumption. Frequency of fish consumption and δ15N was also shown to be positively correlated with mercury concentrations in hair and PCB concentrations in plasma. The results of this thesis demonstrate that known differences in dietary behaviour are clearly reflected in stable isotope ratios and contaminant concentrations. The data also show that contaminant exposures to those consuming wild foods in remote Boreal ecosystems is comparable to those associated with serious health effects in industrialized areas, and the problem of contaminants in wild foods is more widespread than the available literature would have led us to believe. These results affect our appreciation of contaminant exposures to First Nations peoples and will have implications for dietary choices, particularly if individuals are encouraged to consume greater amounts of wild foods for their proposed health benefits. We recommend further attention be given to the risks of contaminants in locally-harvested wild foods when promoting the benefits of their consumption to First Nations people as the problem of contaminants in remote communities practicing traditional lifestyles is often underreported and underplayed.

No description available.

acase@tulane.edu

Le concept de DOHaD (Developmental Origins of Health and Disease) postule que les expositions environnementales subies durant la phase de développement (vie fœtale et premières années de la vie) ont des conséquences majeures sur la santé ultérieure. La diminution du poids de naissance est considérée à la fois comme un marqueur de ces agressions subies par le fœtus au cours de la grossesse et comme un indicateur de la santé future de l’enfant. La recherche en épidémiologie sur les effets de la pollution atmosphérique doit faire face au défi de l’évaluation de l’exposition aux polluants atmosphériques.L’objectif général de cette thèse était de caractériser l’effet des polluants atmosphériques sur la croissance fœtale, en améliorant la caractérisation des expositions et le contrôle des biais de confusion potentiels par rapport aux études antérieures.Dans une première partie, nous avons étudié les déterminants socio-économiques de l'exposition à la pollution de l’air ambiant dans l’étude nationale Française ELFE, incluant 18 000 couples mères-enfants. L'exposition maternelle aux particules fines (PM2,5), PM10 et au NO2 a été estimée à l'adresse du domicile à partir de modèles de dispersion avec des résolutions spatiale (1x1 km) et temporelle (données journalières) fines. En France, dans les zones urbaines, les femmes enceintes des quartiers les plus défavorisés étaient les plus exposées à la pollution atmosphérique.La deuxième partie de ce travail a porté sur la caractérisation de l'association entre les niveaux pollution atmosphérique dans l’air extérieur durant la grossesse et le poids de naissance de l’enfant, toujours dans la cohorte ELFE. Une fois les facteurs de confusion pris en compte à l’aide d’un score de propension, nous avons mis en évidence un effet délétère de l’exposition aux particules en suspension dans l’air au cours du troisième trimestre de grossesse sur le poids de naissance.Dans une troisième partie, nous avons comparé différentes approches pour évaluer l'exposition à la pollution atmosphérique chez la femme enceinte, incluant des mesures personnelles, chez 40 femmes de la cohorte SEPAGES-faisabilité. La considération du budget espace-temps ne modifiait que très légèrement les niveaux d’exposition estimés dans l’air extérieur à l’adresse du domicile. En revanche, l’exposition estimée était fortement modifiée par la prise en compte des niveaux de pollution atmosphérique à l’intérieur du domicile, ou quand l’exposition était l’estimée à l’aide de dosimètres personnels.Ceci a justifié, dans une quatrième partie, d’étudier l'association entre l’exposition à la pollution atmosphérique estimée à l'aide de mesures personnelles et le développement du fœtus dans la cohorte grenobloise SEPAGES, incluant 471 triades couples-enfant. L’exposition personnelle aux PM2,5 (n=174, plus nettement au 1er trimestre) et au NO2 (n=327, plus nettement au 3ème trimestre) étaient associées à une diminution du poids de naissance. L’estimation ponctuelle de l’association avec les PM2,5 était bien plus forte que dans la cohorte ELFE.En conclusion, ce travail vient renforcer la littérature sur l’effet délétère de la pollution atmosphérique sur le poids de naissance. Cette thèse, basée sur deux cohortes complémentaires, a également permis d’illustrer le compromis entre biais et variance entre les études s’appuyant sur des modèles d’exposition extérieurs (pouvant être réalisées sur de vastes zones géographiques permettant des effectifs et contrastes d’exposition larges et avec potentiellement des biais de confusion et d’erreur de mesure sur l’exposition importants) et les cohortes s’appuyant sur des dosimètres personnels (généralement conduites sur des zones plus limitées, dans une population plus homogène, avec moins de biais de confusion potentiels et une meilleure estimation de l’exposition). / The concept of DOHaD (Developmental Origins of Health and Disease) postulates that environmental exposures during the development phase (fetal life and early life) would have major consequences on future health. The reduction in birth weight is considered both as a marker of these aggressions suffered by the fetus during pregnancy and as an indicator of the future health of the child. Epidemiological studies of air pollution effect are challenging in terms of exposure assessment to air pollutants.The general objective of this thesis is to characterize the effect of air pollutants on fetal growth by improving the characterization of exposures and the control of potential confounding biases compared to previous studies.In a first part, we studied the socio-economic determinants of exposure to ambient air pollution in the French national ELFE study including 18000 mother-child couple. Maternal exposure to fine particulate (PM2.5), PM10 and NO2 was estimated using a dispersion model which combined a fine spatial (1x1km grid) and temporal (daily data) resolution. In France, in urban areas, pregnant women in the most socially deprived neighborhoods were the most exposed to air pollution.The second part of this work focused on the characterization of the association between maternal exposure to atmospheric pollution (estimated in outdoor air) and birth weight of the child in the ELFE cohort. Once the confounding factors were taken into account using the propensity score, we highlighted a deleterious effect of exposure to particulate matters during the third trimester of pregnancy on birth weight.In a third part, we compared different approaches to assess exposure to air pollution in pregnant women, including personal measures, in 40 women from the SEPAGES-feasibility cohort. Incorporation of space-time activity only slightly modified the estimated exposure levels in outdoor air to the home address. Conversely, exposure estimates were strongly affected by the incorporation of indoor levels of air pollution or when exposures were assessed using personal dosimeters.This justified, in a fourth part, the study of the association between the exposure to air pollution estimated by personal dosimeters and the fetal growth in the SEPAGES cohort including 471 couples-child triads from the Grenoble urban areas. Personal exposures to PM2.5 (n=174, more strongly during the 1st trimester) and to NO2 (n=327, more strongly during the 3rd trimester) were associated to decreases in birth weight. Our estimates of the association with PM2.5 were stronger than estimates from the ELFE cohort.In conclusion, this work comes to reinforce the literature on the deleterious effect of air pollution on birth weight. This thesis, based on two complementary cohorts, has also illustrated the concept of the compromise between bias and variance between studies using outdoor exposure models (which could be performed on large geographical areas allowing larges sample size and exposure contrasts and with possibly confounders and high degree of exposure misclassification) and cohorts using personal dosimeters (generally conducted on small sample size, in more homogeneous population, with less confounders and better estimation of exposure to air pollution).

No description available.