Identifying toxicity case-reports

Case reports are useful to identify agents that may cause reproductive toxicity. They are probably of greatest use in suggesting topics for further investigation. Reports of clusters and case reports/series are best used in risk assessment in conjunction with strong laboratory data to support the conclusion that similar effects occur in test animals and in humans. 

The lowest LOAEL value (0.083 mg/kg/day) in healthy humans ingesting white phosphorus for an intermediate duration was identified in the Sontag (1938) study. Lower LOAEL values have been identified in children with rickets (Phemister 1918). Because these children had a pre-existing condition, these data were not considered reliable. Other systemic effects and neurological effects were observed at this dose. This study was not selected as the basis of an intermediate-duration oral MRL because it is a case report of a single child and no assessment of hepatic or renal toxicity (liver and kidneys are two primary targets of white phosphorus toxicity) was made. 

Toxic properties are identified in three basic ways through case reports with the tools of epidemiology, and through laboratory studies, typically involving animals but also involving micro-... 

No oral acute MRL was derived for zinc (see Table 2-2 and Figure 2-2). A number of case reports involving acute exposure were located. These reports suggest that the gastrointestinal tract and the pancreas are end points of concern, and that the adrenal cortex may also be affected. A great deal of uncertainty exists regarding the exposure levels for these studies. An oral exposure study in sheep was also identified. Because sheep are ruminants, it is doubtful that they are a good model for human toxicity. 

Parenteral administration of iodinated contrast media to patients taking metformin may result in lactic acidosis. However, the problem is reported to occur only if the contrast media causes renal failure and metformin use is continued. This is because metformin is mainly excreted by the kidneys and in renal failure toxic levels may accumulate, which may result in lactic acidosis. A literature search identified 18 cases of lactic acidosis after the use of contrast media in patients taking metformin. Of these 18 cases, 14 or 15 were associated with pre-existing renal impairment and 2 cases with other contraindications to metformin (sepsis and cirrhosis). The remaining case was in an elderly woman with neurological disease. 

No information on the safety of celandine in pregnancy or lactation was identified. In this work, the contraindications for use in pregnancy and lactation are based primarily on concerns regarding the cases of liver toxicity reported in association with celandine use, as the implications of these case reports, and possible mechanisms of liver toxicity, have yet to be fully understood. 

A systematic review of antipsychotic use in patients with HIV identified one study involving the use of FGAs for the control of delirium and case reports concerning the use of SGAs [24 ]. Increased sensitivity to extrapyramidal symptoms, increased risk of metabolic and bone marrow toxicities and drug-drug interactions with antiretrovirals are discussed. 

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