Toxicity chronic, risk factors

Risk factors from drinking water include infectious disease, acute or chronic chemical toxicity, and carcinogenicity. In 1981, the North Atlantic Treaty Organization Committee on Challenges to Modern... 

Hensley ML, Peterson B, Silver RT, Larson RA, Schiffer CA, Szatrowski TP. Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alfa-2b and low-dose cytarabine for chronic myelogenous leukemia analysis of Cancer and Leukemia Group B 9013. J Clin Oncol 2000 18(6) 1301-8. 

A low pretreatment platelet count, the dose of interferon alfa, and the haptoglobin phenotype are risk factors for ribavirin-induced anemia, and the fall in hemoglobin is independent of dose in the therapeutic range (16). In five patients with chronic hepatitis C on hemodialysis who received subcutaneous interferon alfa-2b and oral ribavirin for 40 weeks, the dose of ribavirin was titrated based on hemoglobin, with bone marrow support by erythropoietin (17). There was significant bone marrow toxicity in all five. A dose of 200 mg/day produced a steady-state AUC comparable to that obtained with 1000-1200 mg/ day in historical controls with normal renal fnnction. More severe anemia was possibly due to chronic renal insufficiency in addition to the prolonged effects of ribavirin. 

In chronic vitamin A ingestion, risk factors for vitamin A toxicity are age, body weight, and renal insufficiency. The hypercalcemia cansed by chronic vitamin A ingestion is explained by npregnlation of osteoclasts by retinol meta-bohtes. 

The pathogenesis includes dehydration secondary to nephrogenic diabetes insipidus, as well as direct proximal and distal tubular cell toxicity resulting in ATN. Chronic tubulointerstitial nephritis attributed to lithium is evidenced most commonly by biopsy findings of interstitial fibrosis, tubular atrophy, and glomerular sclerosis (Presne et al. 2003 SUva 2004). The pathogenesis may involve cumulative direct lithium toxicity since duration of therapy has correlated with the decline in the GFR. The major risk factor for AKI is an elevated lithium concentration, particularly in associatimi with dehydration. 

In accordance with the requirements of Annex VI of 91/414/EEC [7], where the basic principles for decision-making are laid down, Toxicity/Exposure Ratios (TER) are to be calculated. Uncertainty factors of 10 (chronic risk) and 100 (acute risk) must be applied for aquatic organisms. For terrestrial organisms, imcertainty factors of 5 and 10 are to be used, respectively. Different approaches exist for the in-crop area and non-target arthropods and bees in general. Uncertainty arises mainly from the fact that only for a few representative species toxicity data are available. If these trigger values are not breached, a listing of an active substance on Annex I or an authorization of a formulated product respectively are possible. 

For diabetic patients with chronic kidney disease (CKD) stages 1-11 (Creatinine clearance betwem normal and 60 mL/min/1.73 m ), stage-independent actions such as control of cardiovascular risk factors (hypertension, hyperlipidemia, and smoking), avoidance of drug toxicity and diagnostic injury, control of progression, and reduction of proteinuria are essential. 

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