Livelihood intervention and mental well-being among women living with HIV in Delhi.

ABSTRACTPoverty-alleviation programmes aimed to improved mental well-being among persons living with HIV (PLWH) in low and middle income countries have underscored the importance of understanding how and why such programmes work. We present findings from a six-month ethnographic process evaluation of Kiran, an economic livelihood programme locally designed to improve mental well-being among women affected by HIV in Delhi, India. In addition to benefits of improved economic standing, we found that supportive relationships cultivated among participants (n = 9) and with providers (n = 3) provided respite from worry about their illness and reframed what was relationally and practically possible in the context of living with HIV. In acquiring marketable craft skills with peers, participants challenged internalized scripts of being socially devalued and regained agency about their abilities to contribute to their community and support their children's immediate and future needs. We found that the benefits of Kiran weighed less on the direct alleviation of mental distress and more on the instillation of hope for their children. Our findings exemplify the importance of re-visiting a priori theories that inform interventions for PLWH and highlight the methodological merits of ethnographic approaches that underscore how theory and intervention praxis are bidirectionally informed.

Examining Health Literacy Levels in Homeless Persons and Vulnerably Housed Persons with Mental Health Disorders.

Health care use is high in persons who are homeless and vulnerably housed, but their health literacy (ability to read and understand health information) is often not known. The purpose of this study was to determine health literacy rates in a Canadian population of homeless and vulnerably housed individuals with mental health disorders. Higher levels of health literacy were associated with being housed, higher levels of education, non-psychotic mental health diagnoses and lower levels of drug use. This suggests that health literacy may be a potential barrier for accessing and utilizing health services and information for vulnerable populations.

Commentary: IARC Monographs Program and public health under siege by corporate interests.

The International Agency for Research on Cancer (IARC) evaluates causes of cancer with help from independent international experts in an open and transparent manner. Countries, research and regulatory agencies, and other organizations adopt IARC evaluations for communication of human cancer hazards, and for strategies to prevent cancer. Scientists worldwide endorse IARC cancer evaluations and process. Those with economic interests, however, challenge IARC's cancer evaluations, most recently for glyphosate and red and processed meats, and are conducting a campaign including intervention from US Congressional Representatives to discredit IARC's review process and to undermine financial support-a campaign intimidating to IARC and Working Group members. Challenges to scientific interpretations serve to advance science and should be resolved by scientific experts who do not have conflicts of interest. Such interference does not bode well for the free flow of scientific information that informs and protects the public from risks of cancer.

Erratum: "An Integrated Experimental Design for the Assessment of Multiple Toxicological End Points in Rat Bioassays".

[This corrects the article DOI: 10.1289/EHP419.].

An Integrated Experimental Design for the Assessment of Multiple Toxicological End Points in Rat Bioassays.

BACKGROUND: For nearly five decades long-term studies in rodents have been the accepted benchmark for assessing chronic long-term toxic effects, particularly carcinogenicity, of chemicals. The European Food Safety Authority (EFSA) and the World Health Organization (WHO) have pointed out that the current set of internationally utilized test methods capture only some of the potential adverse effects associated with exposures to these agents over the lifetime. OBJECTIVES: In this paper, we propose the adaption of the carcinogenicity bioassay to integrate additional protocols for comprehensive long-term toxicity assessment that includes developmental exposures and long-term outcomes, capable of generating information on a broad spectrum of different end points. DISCUSSION: An integrated study design based on a stepwise process is described that includes the priority end points of the Economic Co-operation and Development and the National Toxicology Program guidelines on carcinogenicity and chronic toxicity and developmental and reproductive toxicity. Integrating a comprehensive set of relevant toxicological end points in a single protocol represents an opportunity to optimize animal use in accordance with the 3Rs (replacement, reduction and refinement). This strategy has the potential to provide sufficient data on multiple windows of susceptibility of specific interest for risk assessments and public health decision-making by including prenatal, lactational, neonatal exposures and evaluating outcomes over the lifespan. CONCLUSION: This integrated study design is efficient in that the same generational cohort of rats used for evaluating long-term outcomes can be monitored in satellite parallel experiments to measure biomarkers and other parameters related to system-specific responses including metabolic alterations and endocrine disturbances. Citation: Manservisi F, Babot Marquillas C, Buscaroli A, Huff J, Lauriola M, Mandrioli D, Manservigi M, Panzacchi S, Silbergeld EK, Belpoggi F. 2017. An integrated experimental design for the assessment of multiple toxicological end points in rat bioassays. Environ Health Perspect 125:289-295; http://dx.doi.org/10.1289/EHP419.

IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

BACKGROUND: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. OBJECTIVES: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. DISCUSSION: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

War on Carcinogens: industry disputes human relevance of chemicals causing cancer in laboratory animals based on unproven hypotheses, using kidney tumors as an example.

Evidence from studies in animals is essential for identifying chemicals likely to cause or contribute to many diseases in humans, including cancers. Yet, to avoid or delay the implementation of protective public health standards, the chemical industry typically denies cancer causation by agents they produce. The spurious arguments put forward to discount human relevance are often based on inadequately tested hypotheses or modes of action that fail to meet Bradford Hill criteria for causation. We term the industry attacks on the relevance of animal cancer findings as the "War on Carcinogens." Unfortunately, this tactic has been effective in preventing timely and appropriate health protective actions on many economically important yet carcinogenic chemicals, including: arsenic, asbestos, benzene, 1,3-butadiene, formaldehyde, methylene chloride, phthalates, tobacco usage, trichloroethylene [TCE], and others. Recent examples of the "War on Carcinogens" are chemicals causing kidney cancer in animals. Industry consultants argue that kidney tumor findings in rats with exacerbated chronic progressive nephropathy (CPN) are not relevant to humans exposed to these chemicals. We dispute and dismiss this unsubstantiated claim with data and facts, and divulge unprofessional actions from a leading toxicology journal.

Long-term toxicology and carcinogenicity of 2,4,6-trichlorophenol.

Carcinogenesis bioassays were conducted by giving 2,4,6-trichlorophenol [2,4,6-TCP] in feed to groups of 50 male and female Fischer rats and male B6C3F1 mice for two years. Dietary concentrations were 0 [20/group], 5000 [0.5%], or 10,000 [1%] ppm. Female mice began with 10,000 and 20,000 ppm but after 38 weeks were lowered due to reduced body weights to 2500 and 5000 ppm for 67 weeks; exposures averaged 5200 and 10,400 ppm. Adverse effects at two years were leukocytosis and monocytosis of peripheral blood and hyperplasia of bone marrow in both sexes of rats. In mice, liver toxicity, including individual liver cell abnormalities, focal areas of cellular alteration, and focal and nodular areas of hyperplasia were commonly present. Regarding carcinogenic activity, TCP caused leukemias/lymphomas in male rats, and possibly in female rats and female mice as well, and induced liver tumors in male and female mice. Using NTP categories of evidence indicates 'clear evidence of carcinogenicity' for male rats [hematopoietic system tumors]; 'equivocal evidence of carcinogenicity' for female rats [hematopoietic system tumors]; 'clear evidence of carcinogenicity' for male and female mice [liver tumors].

Chemically exacerbated chronic progressive nephropathy not associated with renal tubular tumor induction in rats: an evaluation based on 60 carcinogenicity studies by the national toxicology program.

Chronic progressive nephropathy (CPN) is a common age-related degenerative-regenerative disease of the kidney that occurs in both sexes of most strains of rats. Recently, claims have been made that enhanced CPN is a mode of action for chemically induced kidney tumors in male rats and that renal tubular tumors (RTTs) induced by chemicals that concomitantly exacerbate CPN are not relevant for human cancer risk assessments. Although CPN is an observable histopathological lesion that may be modified by diet, the etiology of this disease and the mechanisms for its exacerbation by chemicals are unknown, and it fails to meet fundamental principles for defining carcinogenic modes of action and human relevance. Our comprehensive evaluation of possible relationships between exacerbated CPN and induction of RTTs in 58 carcinogenicity studies, conducted by the National Toxicology Program, in male and 11 studies in female F344 rats using 60 chemicals revealed widespread inconsistency in the claimed association. Because the proposed hypothesis lacks evidence of biological plausibility, and due to inconsistent relationships between exacerbated CPN and kidney tumor incidence in carcinogenicity studies in rats, dismissing the human relevance of kidney tumors induced by chemicals that also exacerbate CPN in rats would be wrong.

Environmental justice and primary prevention of cancer: the odyssey and legacy of lorenzo tomatis.

Lorenzo Tomatis [1929-2007] devoted his private and professional life to the betterment of mankind. As a physician, scientist, and humanitarian he championed against the plight of social injustice and promoted the obvious benefits of primary prevention of diseases compared to treatments that prevent or delay disease progression, especially occupational cancers. An avowed student and scholar of literature, the arts, the history of medicine and science, and chemical carcinogenesis, he believed in and wrote about these issues throughout his storied life. Some of his achievements, with excerpts from his writings, especially on primary prevention and on social injustice, are highlighted herein.

Styrene exposure and risk of cancer.

Styrene is widely used in the manufacture of synthetic rubber, resins, polyesters and plastics. Styrene and the primary metabolite styrene-7,8-oxide are genotoxic and carcinogenic. Long-term chemical carcinogenesis bioassays showed that styrene caused lung cancers in several strains of mice and mammary cancers in rats and styrene-7,8-oxide caused tumours of the forestomach in rats and mice and of the liver in mice. Subsequent epidemiologic studies found styrene workers had increased mortality or incidences of lymphohematopoietic cancers (leukaemia or lymphoma or all), with suggestive evidence for pancreatic and esophageal tumours. No adequate human studies are available for styrene-7,8-oxide although this is the primary and active epoxide metabolite of styrene. Both are genotoxic and form DNA adducts in humans.

Lorenzo Tomatis and primary prevention of environmental cancer.

The leading 20th century proponent for primary prevention of environmental cancer was Dr. Lorenzo Tomatis, the former Director of the International Agency for Research on Cancer and founder of the IARC Monographs program. This paper is dedicated to the memory of Dr. Tomatis--eminent scientist, scholar, teacher, humanitarian, and public health champion--and includes many perspectives that he promoted throughout his career, with original quotations from some of his scientific writings on primary prevention of environmental cancer. Any attempt by us to simply summarize his views would only detract from the power and logic of his language."Cancer still remains a mainly lethal disease. Primary prevention remains the most relevant approach to reduce mortality through a reduction in incidence".

Clarifying carcinogenicity of ethylbenzene.

Ethylbenzene has been evaluated for carcinogenic activity in Fischer rats and B6C3F1 mice exposed by inhalation (Chan et al., 1998; Chan, 1999) and in Sprague-Dawley rats after oral exposure (Maltoni et al., 1985,1997). Bioassay findings are summarized below to expand on those not stated clearly or completely in Saghir et al. (2010). Overall in these three studies animals exposed to ethylbenzene had increased tumors in rats for kidneys, testes, head (including rare neuroesthesioepitheliomas), and total malignant tumors, whilst in mice tumor incidences were increased in the lung and liver (Huff, 2002). Thus ethylbenzene was carcinogenic by two exposure routes to both sexes of two species of rodents, two strains of rats, and one strain of mice, causing collectively tumors in five different target organs and a composite of "total malignant" tumors.