Acute toxicity of some expired insecticides on rats and their effects on some vital parameters and residues in the liver and kidney.

Little information is available on the adverse effects of expired pesticides on the environment, so it is essential to characterize the risk of these chemicals to non-target organisms. Therefore, this work aims to estimate and compare the acute toxicity (LD50) of unexpired and expired formulations of malathion, chlorpyrifos, and lambda-cyhalothrin in rats and to determine their residues in the liver and kidneys of treated rats. This is the first study to investigate the toxic effects of expired pesticides on rats. The acute toxicity of expired lambda-cyhalothrin was higher than that of non-expired rats, while the opposite was observed in rats treated with malathion and chlorpyrifos. All formulations tested caused clinical signs of toxicity in the treated rats. The data showed that some expired formulations significantly affected body weight and estimated vital signs compared to non-expired pesticides. The data showed that the highest residues were found in the liver and kidneys of rats treated with both malathion formulations, followed by chlorpyrifos; however, the lowest residues were found in rats treated with lambda-cyhalothrin, which can be referred to as LD50 values of the insecticides tested. The residues detected after the 10th dose gradually decreased at the end of the recovery period, and their losses ranged from 80.0 to 95.4% in the liver and from 92.3 to 99.99% (undetectable). The results show that the toxic effects of expired and non-expired formulations are different. This underlines the need to dispose of expired compounds carefully to prevent their discharge into the ecosystem.

Sex disparity and drug-induced liver injury.

Drug-induced liver injury (DILI) is a potentially serious clinical condition that remains a major problem for patients, physicians and those involved in the development of new drugs. Population and hospital-based studies have reported incidences of DILI varying from 1.4 to 19.1/100.000. Overall, females have a 1.5- to 1.7-fold greater risk of developing adverse drug reactions and the female/male ratio increases after the age of 49 years, suggesting a clear susceptibility of DILI after menopause. Sex differences in pharmacokinetics and pharmacodynamic, sex-specific hormonal effects or interaction with signalling molecules that can influence drug efficacy and safety and differences in abnormal immune response following drug exposure are the main probable causes of the higher vulnerability observed among female patients. A novel phenotype of autoimmune-mediated DILI following the use of check-point inhibitors in oncology and haematology has been recently described. Finally, there have been increasing reports of DILI associated with use of herbal and dietary supplements that is more frequently reported in women.

Efficacy of doxycycline in the treatment of early stages of mycosis fungoides: a randomized controlled trial.

BACKGROUND: Mycosis fungoides is the most common type of primary cutaneous T cell lymphomas. Doxycycline promoted apoptosis in different human malignant cell lines and in vivo models. OBJECTIVES: To test for the therapeutic efficacy of doxycycline in comparison to PUVA in early stages of classic MF and its effect on T cell apoptosis. METHODS: Thirty-six patients were randomized into either: doxycycline 200 mg daily (n = 18) or PUVA (3 weekly sessions) (n = 18) for 12 weeks. The primary outcome (therapeutic efficacy) was defined in terms of objective response rate (ORR) which was measured according to changes in the modified severity weighted assessment tool (mSWAT). RESULTS: Doxycycline achieved significantly less ORR (partial response) in comparison to PUVA (11.1%, 50%, respectively, p = .016). The percent reduction in mSWAT, CAILS, histopathology score and CD3 expression was significantly less in the doxycycline group (p = .001, p = .001, p ˂ .001, and p = .004, respectively). Within the doxycycline group, changes in mSWAT and CAILS showed no correlation with changes in the CD3 or Bcl-2 expression. Gastric upset was significantly more encountered in the doxycycline group (p = .001). CONCLUSION: Doxycycline is not suitable as a sole agent in the treatment of early stages of classic MF, acting mainly by anti-inflammatory rather apoptotic function. REGISTER NUMBER: NCT03454945 (www.clinicaltrials.gov).

ß-Amyrin supplementation ameliorates the toxic effect of glycerol in the kidney of rat model.

Acute kidney injury (AKI) is a common life-threatening complication. In this study, ß-amyrin is hypothesized to exert a potential nephroprotective effect against glycerol-induced nephrotoxicity in rats. Thirty-two female Sprague-Dawley rats were divided into four groups: normal control, ß-amyrin treated (50 mg kg-1 body weight) for 14 days, glycerol 25% (10 ml kg-1 BW volume/volume in sterile saline, intramuscular), and ß-amyrin + glycerol-treated rats. Assessing kidney function was done through the measurement of serum urea and creatinine (SCr). Real-time quantitative polymerase chain reaction analysis was done to measure the changes in the gap junction protein and intermediate filament proteins (IFPs) messenger RNA (mRNA) levels. Renal tissue histopathology was also observed. Glycerol exhibited significant elevation in the SCr and urea with significant upregulation of connexin43, vimentin, and nestin. The levels of all disrupted parameters were improved by the pre-administration of ß-amyrin. The ß-amyrin exerts significant improvement of the biochemical parameters with a restoration of the renal tissue histopathological picture. Significant downregulation of the expression levels of the gap junction protein and IFPs mRNA was also seen. Collectively, the administration of ß-amyrin showed a promising effect for a protection against glycerol-induced AKI in rats.

Effects of quercetin and rosuvastatin each alone or in combination on cyclophosphamide-induced premature ovarian failure in female albino mice.

BACKGROUND: Cyclophosphamide (CP) causes premature ovarian failure (POF) due to ovarian toxicity. The toxicity mechanism is attributed to oxidative stress, inflammation, and apoptosis. We assessed whether quercetin and rosuvastatin could promote ovarian protection against CP ovotoxicity. METHODS: A total of 80 female BALB/c mice were randomly assigned; 10 mice into each of eight groups. Group 1 (control), group 2 (EH), group 3 (CP), group 4 (QH), group 5 (QL), group 6 (RH), group 7 (RL), and group 8 (COM). RESULTS: Quercetin and rosuvastatin groups (4:8) showed signs of restored ovarian function in the form of a significant, dose-dependent increase in primordial follicles number, serum anti-Mullerian hormone level, and ovarian tissue glutathione level (p < 0.05) versus group 3, and a significant, dose-dependent decrease in atretic follicles number and ovarian tissue level of malondialdehyde (p < 0.05) versus group 3. Immunohistochemistry analysis demonstrated a lower expression of caspase and nuclear factor-kappa B of groups (4:8) versus group 3, although quercetin and rosuvastatin showed a nonsignificant reduction in tumor volume. CONCLUSIONS: We demonstrated the protective effect of quercetin and rosuvastatin against ovarian toxicity and POF induced by CP without compromising its antitumor effect.

Shear Stress Induces Change in Extracellular Signal-Regulated Kinase 5 Levels with Sustained Activation under Disturbed and Continuous Laminar Flow.

Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum-starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to-and-fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber. At the end of experimentation, cell lysates were immunoblotted with antibodies to phospho-ERK5 and total ERK5. ERK5 activation was assessed by the levels of phosphorylated ERK5. The densitometric mean ± SEM is calculated and analyzed by ANOVA. p < 0.05 is considered significant. Levels of ERK5 decreased with all flow conditions with the largest decrease in TFF flow condition. TFF and CLF exhibited sustained ERK5 phosphorylation in HUVECs stimulated for up to 4 hours. PFF had transient phosphorylation of ERK5 at 2 hours, which then became undetectable at 4 hours of exposure to flow. Also, TFF and CLF both showed decreased levels at 4 hours, suggesting a decrease in activation for these flow conditions. Exposure of HUVEC to different types of shear stress results in varying patterns of activation of ERK5. Activation of ERK5 with TFF suggests a role in the pathogenesis of atherosclerosis and vascular remodeling under disturbed flow conditions.

Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment of localized scleroderma: a clinical and immunohistochemical randomized controlled study.

Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm2) UVA-1 phototherapy (340-400 nm) or 3 sessions of fractional CO2 laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO2 laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

Seasonal changes in some oxidant and antioxidant parameters during folliculogenesis in Egyptian buffalo.

Knowledge regarding oxidant and antioxidant status in follicular fluid remains limited and its studying in vivo should enhance our understanding of the impact of them on fertility and contribute to optimization of in vitro maturation conditions. The present study was conducted on follicular fluid and serum samples obtained from 708 buffaloes. They were examined for Malondialdehyde (MDA) as indicator of lipid peroxidation as well as superoxide dismutase (SOD) and total antioxidant capacity (TAC) as antioxidant markers. The obtained results revealed that MDA levels and SOD activity in follicular fluid decreased significantly as follicle size increased, while TAC increased significantly with the increase in follicular size. Whereas MDA level was significantly higher in summer, the TAC was significantly higher in spring. Moreover, MDA levels and SOD activities were significantly higher in the follicular fluid from different size follicles during the luteal phase than follicular phase. MDA levels in medium follicles in luteal phase and small follicles in follicular and luteal phases were significantly higher in summer than other seasons. Serum MDA levels were significantly increased in summer. In addition, MDA levels, SOD activities and TAC in serum were significantly higher during luteal phase than follicular phase in summer. TAC levels were significantly higher in follicular fluid than serum, while MDA was significantly lower in follicular fluid than serum. In conclusion, the present study revealed that oxidants/antioxidants balance may play a role in normal follicular development and oxidative stress that occur in summer could be related to reproductive seasonality in buffalo.

Association of serum cytokines levels, interleukin 10 -1082G/A and interferon-γ +874T/A polymorphisms with atopic asthma children from Saudi Arabia.

The aim of this study was to clarify the role of IL-4, IL-10, IL-13 and interferon (IFN) -γ levels in atopic asthma patients by studying the relation between their serum levels and severity of the disease. The effect of IL-10 -1082G/A and IFN-γ +874T/A SNPs was also studied. The study included 200 atopic children with asthma and 50 age- and gender matched healthy children as controls. The levels of both IL-4 and IL-13 were significantly (p<0.001) higher, while IFN-γ was significantly (p<0.001) lower in patients compared to that of the controls. There was a significant effect of gene polymorphisms of IL-10 (p<0.05) and IFN-γ (p<0.001) in occurrence of atopic asthma and increased IgE level. Polymorphism of IFN-γ gene had an effect on the serum level of IFN-γ. In conclusion, IFN-γ gene polymorphism at position +874 and IL-10 gene polymorphism at position -1082A/G are genetic determinants which contribute to susceptibility to atopic asthma in children from Saudi Arabia.

Cyclooxygenase-2 169C>G and 8473T>C gene polymorphisms and prostaglandin E2 level in breast cancer: a case-control study.

AIMS: Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G and 8473T>C gene polymorphisms and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC. METHODS: The study population comprised 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP. RESULTS: The variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR=3.1, 95% CI (2.2-4.4), P<0.001 for 169C>G and OR=1.74, 95%CI (1.3-2.4), P=0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P<0.001) for 169 C>G, also towards the presence of CC than TT (P<0.001) for 8473T>C SNP. CONCLUSION: The 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.

1'-Methyl-4'-(4-methyl-phen-yl)dispiro-[indane-2,3'-pyrrolidine-2',3''-indoline]-1,2''-dione.

In the title mol-ecule, C(27)H(24)N(2)O(2), the pyrrolidin-2-one ring is almost planar (r.m.s. deviation = 0.003 Å), the pyrrolidine ring has an envelope conformation (the N atom is the flap atom) and the cyclo-penta-none ring is twisted about the C(q)-C(m) bond (q = quaternary and m = methylene). The ketone O atoms are directed to opposite sides of the mol-ecule. Supra-molecular chains along the a axis are formed in the crystal packing mediated by N-H⋯N and C-H⋯O inter-actions. These are connected into layers in the ab plane via C-H⋯π inter-actions.

Interleukin 13 receptors as biochemical markers in atopic patients.

BACKGROUND: Interleukin (IL) 13, a type 2 helper T cell (T(H)2), is an important regulator of inflammatory immune responses. It mediates its action through a receptor complex consisting of IL-13Ralpha1 and IL-4Ralpha. IL-13Ralpha2 binds IL-13 with high affinity and is thought to act primarily as a decoy receptor, sequestering IL-13 and thus inhibiting its action. Our aim was to clarify the role of these receptors in the diagnosis and follow-up of atopic patients. METHODS: We genotyped the 1398A>G polymorphism in the IL-13Ralpha1 gene using restriction fragment length polymorphism for causal genetic diversity and measured serum levels of IL-13Ralpha2 in 105 atopic patients suffering from atopic asthma, atopic dermatitis, and atopic rhinitis (35 each). We compared the results with those of 35 nonatopic control individuals. Total immunoglobulin (Ig) E and serum IL-13Ralpha2 were measured using enzyme-linked immunosorbent assay, and the eosinophil counts were recorded. RESULTS: A significant increase in serum IL-13Ralpha2 levels was recorded in the 3 atopic groups compared with the control group (P < .001), as well as a significant increase in total IgE levels and eosinophil counts. No significant association was found between 1398A>G and atopy other than a suggestive association between this polymorphism and raised total serum IgE levels in all 3 atopic groups (P < .001). CONCLUSIONS: These findings indicate that IL-13Ralpha2 plays an important role in atopy and that increased levels in different groups highlight its regulatory role in the development of atopic symptoms. The 1398A>G polymorphism might be involved in the production of IgE.

Interleukin 10 receptor alpha subunit (IL-10RA) gene polymorphism and IL-10 serum levels in Egyptian atopic patients.

OBJECTIVES: To assess the value of serum interleukin (IL) 10 levels as an immunological marker in atopy and to determine the role of an IL-10RA gene single nucleotide polymorphism (SNP) (serine 138-to-glycine exchange [S138G]) in the pathogenesis of atopic diseases. METHODS: Seventy-five patients with atopic disorders were compared with 25 age-matched healthy volunteers. Serum total immunoglobulin (Ig) E and IL-10 levels were measured by enzyme-linked immunosorbent assay and the IL-10RA gene S138G variant was screened by multiplex allele-specific polymerase chain reaction. RESULTS: There was a significant association between G allele frequencies of the S138G variant (62%, 60% and 68% for atopic asthma, atopic dermatitis, and allergic rhinitis, respectively) in atopic patients compared to in controls. There were significant differences in mean IgE levels but not mean serum IL-10 levels between the allelic variants in atopy groups. CONCLUSION: The IL-10RA gene SNP S138G may contribute to susceptibility to atopic diseases but serum IL-10 level is not a sensitive indicator in atopy.

Hepatitis B and C viral infection: prevalence, knowledge, attitude and practice among barbers and clients in Gharbia governorate, Egypt.

A study in Egypt determined the prevalence of hepatitis B and C virus infections among barbers (n = 308) and their clients (n = 308) in Gharbia governorate, and assessed knowledge, attitude and practices during hair-cutting and shaving. HBsAg was detected among 4.2% of barbers and 3.9% of clients (more urban than rural). Anti-HC antibodies were detected in 12.3% of barbers and 12.7% of clients. HCV-RNA prevalence was 9.1% among both barbers and clients (more rural than urban). Knowledge was high among the majority of participants and good practices during shaving and hair-cutting were observed for the majority of barbers. Barbers appeared to have no job-related risk of acquiring viral hepatitis.

Interferon gamma gene polymorphism as a biochemical marker in Egyptian atopic patients.

OBJECTIVES: The aim of this study was to clarify the role of interferon (IFN) gamma in the diagnosis and follow-up of atopic patients. We genotyped the IFN-gamma polymorphism at position +874 to examine the relationship between serum levels of IFN-gamma and disease severity and the role of IFN-gamma as a biochemical and immunologic marker. METHODS: The study population comprised 75 patients suffering from atopic asthma, atopic dermatitis, and allergic rhinitis (25 each), and 25 control participants. Total immunoglobulin (Ig) E and serum IFN-gamma were measured by enzyme-linked immunosorbent assay, the IFN-gamma polymorphism at position +874 was determined by amplification refractory mutation system-polymerase chain reaction, and eosinophil counts were recorded. RESULTS: There was a significant association between genotype and the frequency of the A allele of the +874T/A polymorphism in atopic patients when compared with controls (P < .001). In all 3 groups, there was a significant increase in total IgE levels and eosinophil counts, and a decrease in serum IFN-gamma levels towards the presence of homozygous AA compared with homozygous TT. CONCLUSIONS: The IFN-gamma gene polymorphism at position +874 contributes to susceptibility to atopic diseases by decreasing the amount of IFN-gamma. Identification of variants of IFN-gamma gene signalling and its role in the development of atopic diseases provides a focus for the development of novel diagnostic and therapeutic strategies for these diseases.

Limb salvage for osteosarcoma of the distal tibia with resection arthrodesis, autogenous fibular graft and Ilizarov external fixator.

We report the results of limb salvage for non-metastatic osteosarcoma of the distal tibia using resection arthrodesis, autogenous fibular graft and fixation by an Ilizarov external fixator. In six patients with primary osteosarcoma of the distal tibia who refused amputation, treatment with wide en bloc resection and tibiotalar arthrodesis was undertaken. The defect was reconstructed using non-vascularised free autogenous fibular strut graft in three patients and a vascularised pedicular fibular graft in three, all supplemented with iliac cancellous graft at the graft-host junction. An Ilizarov external fixator was used for stabilisation of the reconstruction. In five patients sound fusion occurred at a mean of 13.2 months (8 to 20) with no evidence of local recurrence or deep infection at final follow-up. The mean post-operative functional score was 70% (63% to 73%) according to the Musculoskeletal Tumour Society scoring system. All five patients showed graft hypertrophy. Union of the graft was faster in cases reconstructed by vascularised fibular grafts. One patient who had a poor response to pre-operative chemotherapy developed local tumour recurrence at one year post-operatively and required subsequent amputation.

The growth of chondrocytes into a fibronectin-coated biodegradable scaffold.

Porous scaffolds made from a biodegradable copolymer of trimethylene carbonate and glycolide were evaluated for tissue-engineered medical products. We examined the scaffold coated with cell adhesion protein and fibronectin and cultured under a dynamic mixing condition to enhance the growth of chondrocytes. Our hypothesis was that the combination of coating and dynamic mixing would be beneficial to the viability of the chondrocytic cells. Fibronectin was selected as the model protein because of its availability and routine assaying methods. Sterile samples of scaffolds of about 1 mm in thickness were coated with fibronectin at 37 degrees C for 1.5 h. Four groups of scaffolds were used: uncoated static or dynamic, and coated static or dynamic. Scaffold samples were placed in either a Petri dish or a spinner flask (static vs. dynamic groups) after inoculation with rat chondrocytes of an initial cell density of 1.29 x 10(5) cell/mL. After 7, 14, 21, and 28 days, each sample was fixed, embedded, and sectioned at 5 micro thickness. The sections were double-label immunostained using antibodies against cellular fibronectin synthesized by adherent cells as a measure of cell viability. A Hoechst 33258 nuclear stain was used to measure the number of cells attached to the scaffold at each time interval. The slides were examined using a fluorescence microscope to determine the cell ingrowth. At least 25 fields/treatment group (except the 7 day group) were measured. The data showed that cell in-growths into the porous scaffolds were higher at all time periods for the coated dynamic group than those for the other three groups.

Long-term gamma irradiation effects on ultrahigh molecular weight polyethylene.

Effects of gamma irradiation, irradiation environment, and long-term postirradiation aging on thermal behavior, crystallinity, mechanical properties, and weight change of ultrahigh molecular weight polyethylene (UHMWPE) were investigated. The gamma irradiation was conducted at 2.5 Mrad under four different environments, i.e., air, nitrogen, acetylene, and vacuum. The postirradiation aging effects were monitored over a period of 5.5 years. The results showed that gamma irradiation, irradiation environments, and postirradiation aging significantly changed the properties of UH-MWPE. After gamma irradiation, the melting temperature and crystallinity of UHMWPE were increased in all cases, with the highest increase at longest postirradiation aging time. Gamma irradiation and postirradiation aging caused weight gain of UHMWPE in all conditions. The tensile and flexural properties were significantly affected by gamma irradiation. At 5.5 years postirradiation, tensile-tested UHMWPE specimens fractured in brittle form, indicating dramatic reduction in the material's toughness. This kind of behavior may be detrimental to UHMWPE load-bearing orthopedic devices for their intended long-term applications.

Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae). IV. Toxicologic and pathophysiologic observations in lactating goats and their suckling kids fed on the irritant herbs Euphorbia nubica and Euphorbia helioscopia: an etiologic model for investigations on the putative risk of cancer by consumption of food p.

The feeding of lactating goats on usual green fodder, contaminated with Euphorbia helioscopia or E. nubica, results in poisoning of the dams as well as their suckling kids. General signs of toxicity were emaciation, depression, shedding of body hair, arching of back, and possible death. Post-mortem changes of dams and dead suckling kids included congestion and hemorrhage in cardiac muscle, lung, liver, and kidneys. Blood analyses of goats exposed to these contaminants showed an increased level of serum alanine amino transferase compared to control samples, indicating cellular destruction in the liver. The latter was confirmed by histopathological changes in the organ which include severe congestion, necrosis, and degenerative changes. The goats also suffered from deterioration of renal function as indicated by increased blood urea nitrogen and creatinine levels. In histopathologic inspections of kidney, severe congestion, hemorrhage in the cortex and medulla, as well as necrosis of epithelial cells of kidney tubules were noticed. Considerable degenerative changes were also observed in heart and lung. The pathophysiological appearances indicate that by feeding on the Euphorbia species mentioned above, the goats are poisoned in a way similar to the case of E. peplus reported previously. Such intoxication most likely is due to irritant and hyperplasiogenic diterpene ester (DTE) toxins, usually present in the aerial parts of Euphorbia species and well known as tumor promoters in mouse skin. After ingestion of the toxic plant parts by the goats, the DTE toxins might be metabolized and thereby partially detoxified. Yet, at least in part, they may show up in the milk of the goats, as indicated by severe poisoning of their suckling kids. As discussed previously in lactating goats fed on fodder contaminated with E. peplus, tumor promoters of the DTE type may enter the human food chain via this source of milk. Such milk may be considered a valuable etiologic model for the investigation of economic, ecologic, and public health problems raised by human diet polluted with tumor promoters, i.e., conditional (non-genotoxic) cancerogens.