Toxicity delayed

Starvation or disease can lead to rapid release of the stored xenobiotic and to delayed toxic effects. In one well-documented case in the Netherlands (see Chapter 5), wild female eider ducks (Somateria mollissima) experienced delayed neurotoxicity caused by dieldrin. The ducks had laid down large reserves of depot fat before breeding, and these reserves were run down during the course of egg laying. Dieldrin concentrations quickly rose to lethal levels in the brain. Male eider ducks did not lay down and mobilize body fat in this way and did not show delayed neurotoxicity due to dieldrin. 

Temporal Relationships of Adverse Events. The temporal relationship between duration of product exposure and development of an adverse event is important in assessing causality. But how can data on temporal relationships be systematically summarized in a database containing thousands or even hundreds of thousands of subjects Temporal relationships cannot be clearly elicited if only frequencies of adverse events between treatment and control groups are compared. There can be many disparities in the subjects time of exposure or time at risk. Toxic manifestations of drugs may not occur until several months or even years after the initial exposure to the drug. How do we systematically assess delayed toxicity of a previously prescribed drug from the effect of a newly prescribed drug Such a scenario occurred with reported cases of pancreatitis associated with valproic acid therapy, in which some cases appeared several years after therapy [2]. 

Chen CH, Vazquez-Padua M et al (1991) Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. Mol Pharmacol 39(5) 625-628... 

There are no definitive data regarding the metabolism of arsine. Based upon proposed mechanisms of action and the known interaction with RBCs and hemoglobin, metabolism per se may of limited importance relative to acute exposures to arsine. Delayed toxicity and lethality are observed in both humans and animals following acute exposure to arsine, and it is known that increased... 

Jash, N.B. and S. Bhattacharya. 1983. Delayed toxicity of carbofuran in freshwater teleosts, Channapunctatas (Bloch) and Anabas testudineus (Bloch). Water Air Soil Pollut. 19 209-213. 

Episodic pollution events can adequately be addressed by acute toxicity bioassays, however these are not sufficient to investigate the water quality for delayed toxicity effects of chemicals present. Chronic effects of pesticides can include carcinogenicity, teratogenicity, mutagenicity, neurotoxicity, and reproductive effects (endocrine disruption). 

Slow poisoning can occur in several different ways. In some cases, chemicals or their metabolites may slowly accumulate in the body -rates of excretion are lower than rates of absorption - until tissue and blood concentrations become sufficiently high to cause injury. Delayed toxicity can also be brought about by chemicals that do not accumulate in the body, but which act by causing some small amount of damage with each visit. Eventually, these small events, which usually involve... 

Knowledge of which mechanism of delayed toxicity is operating in specific cases cannot usually be gained from the animal test or from epidemiology studies additional studies of ADME, and of pharmacodynamic interactions of the chemical with cellular components, are necessary to understand mechanisms of delayed toxicity. Some mechanisms are discussed in the following to illustrate the value of this kind of study. 

People who suffer from other pulmonary diseases that interrupt the flow of oxygen are especially sensitive to the irritating effects of SO2 and its particulate derivatives. This gas and several other gaseous air pollutants, to be mentioned in a moment, can cause other, delayed toxic effects in the respiratory system. Note also that these same chemicals are the principal causes of acid rain. 

Delayed toxicity is another legitimate concern. Subtle adverse effects are... 

The three compounds of series (I), namely SOF, SOPHi and SOAz, are found to be active, but DISOF does not exhibit any antitumor activity at all. The delayed toxicity of DISOF may however conceal an eventual antitumoral activity. It appears therefore that at least two geminal aziridino pairs are necessary in these compounds for antitumoral activity. 

Hemoperfusion is like hemodialysis except that blood is circulated extracorporeally through a column with adsorbent material like resin or charcoal, which binds molecules electrostatically. The molecules likely to be removed are characterized as poorly dialyzable, lipid-soluble, protein bound. Among the indications for hemoperfusion in the management of poisoning include the presence of a poison in a patient with impairment of excretory system (i.e. damaged kidneys), intoxication of a drug known to produce delayed toxicity or metabolized to a more toxic metabolite (i.e. paraquat or methotrexate), deterioration of the clinical state of the poisoned patient despite conservative therapy (i.e. convulsions or cardiac arrhythmias following theophylline intoxication), or development of coma as a complication. 

Foekema, E.M., Deerenberg C., Murk, A.J. (2008). Prolonged ELS test with the marine flatfish sole (Solea solea) shows delayed toxic effects of previous exposure to PCB 126, Aquatic Toxicology, 90 197-203. 

Lohs, K. 1975. Delayed Toxic Efects of Chemical Warfare Agents. Stockholm Stockholm International Peace Research Institute and Almqvist and Wilksell International. 1975. 60 p. 

Alkylating Agent Mechanism of Action Clinical Applications Acute Toxicity Delayed Toxicity... 

ThiolMP and ThioGMP are feedback inhibitors of phosphoribosylpyrophosphate amido-transferase, which is the first, and rate-limiting step in the synthesis of purine. In addition, these analogs inhibit the de novo biosynthesis of purine and block the conversion of inosinic acid to adenylic acid or guanylic acid. The triphosphate nucleotides are incorporated into DNA, and this results in delayed toxicity after several cell divisions. 

---