Key issues for the assessment of the allergenic potential of genetically modified foods: breakout group reports.

On the final afternoon of the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods," held 10-12 December 2001 in Chapel Hill, North Carolina, USA, speakers and participants met in breakout groups to discuss specific questions in the areas of use of human clinical data, animal models to assess food allergy, biomarkers of exposure and effect, sensitive populations, dose-response assessment, and postmarket surveillance. Each group addressed general questions regarding allergenicity of genetically modified foods and specific questions for each subject area. This article is a brief summary of the discussions of each of the six breakout groups regarding our current state of knowledge and what information is needed to advance the field

Assessment of immunotoxicity in the 21st century: where we are and what we need to replace animals

The field of immunotoxicity assessment has traditionally relied on animal models, which have raised ethical concerns and presented limitations in terms of predictive accuracy and relevance to human health. This paper reviews the current state of immunotoxicity evaluation, emphasizing the importance of transitioning away from animal testing. Modern approaches, including in vitro methods, human-based studies, adverse outcome pathways (AOPs), and computational modeling, are discussed as viable alternatives. These non-animal methods offer enhanced predictive power and the potential for regulatory acceptance, though technical and practical challenges remain. Case studies demonstrate the success of non-animal methods, such as AOPbased assessments for skin sensitization and the pyrogen assay using whole blood cytokine assays. Despite these advances, further research is needed in areas like respiratory sensitization, developmental immunotoxicology (DIT), and microphysiological systems (MPS). Recommendations are provided to accelerate the adoption of new approach methodologies (NAMs), focusing on AOP frameworks. In conclusion, the paper highlights the key findings from current non-animal immunotoxicity research and issues a call to action for advancing these methods to improve safety assessment practices in the 21st century

Assessment of allergenic potential of genetically modified foods: an agenda for future research.

Speakers and participants in the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods" met in breakout groups to discuss a number of issues including needs for future research. These groups agreed that research should progress quickly in the area of hazard identification and that a need exists for more basic research to understand the mechanisms underlying food allergy. A list of research needs was developed

Associations between Plasma DDE Levels and Immunologic Measures in African-American Farmers in North Carolina

Experimental studies in rodents demonstrate evidence of immunosuppressive effects of dietary exposure to DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane], but human data pertaining to immunomodulating effects of DDT exposure are limited. In this study we examined the association between the persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p-chlorophenyl)ethylene (p,p′-DDE) and immunologic measures using blood samples in a relatively highly exposed population of farmers in the United States. Levels of serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies in relation to plasma p,p′-DDE levels were evaluated in samples from 137 African-American male farmers (30–88 years of age; median, 64 years). Participants were recruited through black churches in four rural counties in eastern North Carolina. Data collection included a telephone interview pertaining to farming practices and health history, and one blood sample was collected from each participant. Linear and logistic regression, adjusting for age, cholesterol, triglycerides, smoking status, and years of any kind of pesticide use, was used to assess the association between immunologic parameters and plasma levels of p,p′-DDE. The median plasma p,p′-DDE concentration was 7.7 μg/L (range, 0.6–77.4 μg/L). There was no association between p,p′-DDE and IgA in any of the models. IgG levels decreased with increasing p,p′-DDE levels, with a statistically significant decrease of approximately 50% in the highest two categories of exposure (≥ 6.0 μg/L) compared with values of < 3.0 μg/L. Sixteen (12%) were positive for antinuclear antibodies. The prevalence of antinuclear antibodies was somewhat elevated in the highest category of p,p′-DDE exposure (odds ratio, 1.9; 95% confidence interval, 0.32–11.3; for ≥ 12.0 μg/L compared with < 3.0 μg/L p,p′-DDE), but this difference was not statistically significant. These analyses provide evidence that p,p′-DDE modulates immune responses in humans

Biokinetics and Subchronic Toxic Effects of Oral Arsenite, Arsenate, Monomethylarsonic Acid, and Dimethylarsinic Acid in v-Ha-ras Transgenic (Tg.AC) Mice

Previous research demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment increased the number of skin papillomas in v-Ha-ras transgenic (Tg.AC) mice that had received sodium arsenite [(As(III)] in drinking water, indicating that this model is useful for studying the toxic effects of arsenic in vivo. Because the liver is a known target of arsenic, we examined the pathophysiologic and molecular effects of inorganic and organic arsenical exposure on Tg.AC mouse liver in this study. Tg.AC mice were provided drinking water containing As(III), sodium arsenate [As(V)], monomethylarsonic acid [(MMA(V)], and 1,000 ppm dimethylarsinic acid [DMA(V)] at dosages of 150, 200, 1,500, or 1,000 ppm as arsenic, respectively, for 17 weeks. Control mice received unaltered water. Four weeks after initiation of arsenic treatment, TPA at a dose of 1.25 μg/200 μL acetone was applied twice a week for 2 weeks to the shaved dorsal skin of all mice, including the controls not receiving arsenic. In some cases arsenic exposure reduced body weight gain and caused mortality (including moribundity). Arsenical exposure resulted in a dose-dependent accumulation of arsenic in the liver that was unexpectedly independent of chemical species and produced hepatic global DNA hypomethylation. cDNA microarray and reverse transcriptase–polymerase chain reaction analysis revealed that all arsenicals altered the expression of numerous genes associated with toxicity and cancer. However, organic arsenicals [MMA(V) and DMA(V)] induced a pattern of gene expression dissimilar to that of inorganic arsenicals. In summary, subchronic exposure of Tg.AC mice to inorganic or organic arsenicals resulted in toxic manifestations, hepatic arsenic accumulation, global DNA hypomethylation, and numerous gene expression changes. These effects may play a role in arsenic-induced hepatotoxicity and carcinogenesis and may be of particular toxicologic relevance

Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral Infection in Mice

BACKGROUND: We previously demonstrated that cyclooxygenase (COX)-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560), a COX-2 inhibitor (celecoxib) or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU) and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL) fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice

A statement on the developmental immunotoxicity of bisphenol A (BPA) : answer to the question from the Dutch Ministry of Health, Welfare and Sport

The Panel wishes to thank EFSA staff member Cristina Croera for the support provided to this scientific opinion.Publisher PD