Pathology considerations for, and subsequent risk assessment of, chemicals identified as immunosuppressive in routine toxicology

Basketter, D.A.; Bremmer, Jan Ν.; Buckley, Patrick J.; Kammüller, Michael; Kawabata, Takami; Kimber, Ian; Loveless, Scott E.; Magda, S.; Stringer, D.A.; Vohr, Hans-Werner

doi:10.1016/0278-6915(94)00128-b

Cited by 38 publications

(20 citation statements)

References 13 publications

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“…Nevertheless, we cannot point out a potentially causal relationship for the augmented kidney weight in treated animals. Yet our ndings showed neither histopathological alterations nor differences in renal function evaluated by relevant pathophysiological markers, as urea and creatinine plasma concentration (Basketter et al 1995). Furthermore, there is no evidence of sevourane-nephrotoxic effects in mouse or rat models (Frink et al 1992, Malan et al 1993.…”

Section: Discussionmentioning

confidence: 98%

Effects of repetitive sevoflurane anaesthesia on immune response, select biochemical parameters and organ histology in mice

et al. 2003

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SummaryAnimal and technical models often require repeated anaesthetic administrations for surgical procedures. As there is evidence for immunomodulatory effects of anaesthesia, the effects of repeated exposure to sevo urane anaesthesia on the immune response in mice were studied. Sevo urane was administered in vivo under conditions that simulate those in clinical procedures. Adult male mice were anaesthetized with 3% sevo urane in oxygen for 40 min weekly for 3 weeks. Untreated animals served as controls. After sevo urane anaesthesia, peripheral blood leukocyte counts, the composition and in vitro function of spleen cells (lymphocytes and macrophages) and the in vivo immune response to a conventional T-dependent antigen were assessed. In addition, liver, spleen and kidney histopathology and also hepatic and renal function were studied. Three days after the latest anaesthetic procedure, the absolute number of both leukocyte and lymphocyte counts were reduced in peripheral blood. Splenic cell composition (LB, LTCD3‡ , LTCD4 ‡ and LTCD8 ‡ ), macrophage function and the mitogen-induced lymphoprolipherative response were preserved. Yet, the in vivo humoral response to a conventional antigen was augmented following the antigenic challenge. Assessment at day 9 after the last anaesthetic procedure revealed the persistence of the humoral response alteration. Nevertheless, sevo urane-treated animals showed no evidence of histological changes or alteration in hepatic or renal function.

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Section: Discussionmentioning

confidence: 98%

Effects of repetitive sevoflurane anaesthesia on immune response, select biochemical parameters and organ histology in mice

et al. 2003

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“…Thus, the following standard clinical and anatomic pathology markers will be included in the 28-day rat study and 90-day dog study specifications: serum biochemical markers such as globulin levels, hematology (including differential), gross pathology findings, immune system-related organ weights, and histologic examination of immune system-related tissues (Basketter et al, 1995).…”

Section: Immunotoxicitymentioning

confidence: 99%

“…In addition, the lymphoid tissue that drains or contacts the site of chemical administration (and therefore is likely to be exposed to the highest concentration of the material) should be specifically examined (Basketter et al, 1995). These sites include the gutassociated lymphoid tissues (GALT) for orally administered materials, bronchus-associated lymphoid tissues (BALT), and nasal-associated lymphoid tissues (NALT) for materials administered by the inhalation route, and the regional draining lymph nodes for chemicals administered by the dermal route.…”

Section: Immunotoxicitymentioning

confidence: 99%

A Tiered Approach to Systemic Toxicity Testing for Agricultural Chemical Safety Assessment

Doe

Boobis

Blacker

et al. 2006

Critical Reviews in Toxicology

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A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. The ACSA Systemic Toxicity Task Force proposes an approach to systemic toxicity testing as one part of the overall assessment of a compound's potential to cause adverse effects on health. The approach is designed to provide more relevant data for deriving reference doses for shorter time periods of human exposure, and includes fewer studies for deriving longer term reference doses-that is, neither a 12-month dog study nor a mouse carcinogenicity study is recommended. All available data, including toxicokinetics and metabolism data and life stages information, are taken into account. The proposed tiered testing approach has the potential to provide new risk assessment information for shorter human exposure durations while reducing the number of animals used and without compromising the sensitivity of the determination of longer term reference doses.

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“…Altered thymic morphology and function have been associated with immunotoxicity caused by a variety of agents and changes in thymus architecture, (17,18). In addition to the thymus, a thorough evaluation of lymphoid tissues should include examination of the spleen, lymph nodes local and distal to the site of exposure, the bone marrow, and hematology (1).…”

Section: Lymphoid Tissuementioning

confidence: 99%

“…Although it is probably the case that the application of more sophisticated (enhanced) immunopathology would increase the sensitivity of histopathological approaches, there is some debate about whether, in isolation, standard examinations of the weight, architecture and cellularity of lymphoid tissues are of suf cient sensitivity to serve alone as a rst tier of immunotoxicity testing (1,8,20). For this reason there has been considerable interest in the application of immune function tests and related approaches.…”

Section: Lymphoid Tissuementioning

confidence: 99%

Immune Responses: Adverse Versus Non-Adverse Effects

Kimber

Dearman

2002

Toxicol Pathol

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The adaptive immune system in vertebrates has evolved to provide host resistance to infectious microorganism s and malignant disease. Normal immune function and the induction of speci c immune responses require the orchestrated interaction between cells and molecules both within and outside the lymphoid system. Immunotoxicolog y can be de ned as the study of adverse health effects that may result from the interaction of xenobiotics with the immune system. In general terms such effects can take one of two forms. The rst of these is immunotoxicity (or immunosuppressio n) where there is a perturbation of, or damage to, one or more component s of the immune system resulting in impaired immune function and reduced host resistance. The design and interpretation of experimental immunotoxicity studies and the investigation of clinical immunosuppressio n require consideration of the relationship between changes in the structure and/or function of discrete component s of the immune system and holistic changes in the susceptibility to infectious and malignant disease. The other main way in which chemicals may cause adverse health effects secondary to interaction with the immune system is through stimulation of speci c immune responses that result in allergic disease. Allergy to chemicals and proteins can take many forms, including allergic contact dermatitis, allergic sensitization of the respiratory tract (associated with rhinitis and/or asthma), systemic allergic reactions (associated frequently with drug treatment), and gastrointestinal disease. Here there is a need to distinguish between immunogeni c responses per se and those immune responses that are of suf cient vigor and of the quality necessary to provoke allergic sensitization. The purpose of this article is to explore the extent to which distinctions can be drawn between adverse and nonadverse effects in the context of immunotoxicit y and allergy.

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Pathology considerations for, and subsequent risk assessment of, chemicals identified as immunosuppressive in routine toxicology

Cited by 38 publications

References 13 publications

Effects of repetitive sevoflurane anaesthesia on immune response, select biochemical parameters and organ histology in mice

Effects of repetitive sevoflurane anaesthesia on immune response, select biochemical parameters and organ histology in mice

A Tiered Approach to Systemic Toxicity Testing for Agricultural Chemical Safety Assessment

Immune Responses: Adverse Versus Non-Adverse Effects

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