Exposure similarities

Practically all toxicokinetic properties reported are based on the results from acute exposure studies. Generally, no information was available regarding intermediate or chronic exposure to methyl parathion. Because methyl parathion is an enzyme inhibitor, the kinetics of metabolism during chronic exposure could differ from those seen during acute exposure. Similarly, excretion kinetics may differ with time. Thus, additional studies on the distribution, metabolism, and excretion of methyl parathion and its toxic metabolite, methyl paraoxon, during intermediate and chronic exposure are needed to assess the potential for toxicity following longer-duration exposures. 

Cyanide metabolizes in the human body to thiocyanate, and its biodegradation products include ammonia, carbon dioxide, nitrate, or nitrogen (Richards and Shieh 1989). The detection of thiocyanate in body fluids may indicate cyanide exposure. Similarly, the amounts of cyanide degradation products formed in an environmental medium could be used to measure cyanide s biodegradation rate. A summary of methods for determining environmental degradation products is shown in Table 6-4. Suitable analytical methods are available to detect all of these compounds (Pettigrew and Fell 1973 Richards and Shieh 1989). 

In contrast to animal studies, epidemiological studies of workers employed in the manufacture of aldrin provide no conclusive evidence of carcinogenicity in humans. " One study of a cohort having mixed exposure to aldrin, dieldrin, and endrin found 9 deaths from cancer versus 12 expected. The workers had been exposed to the pesticides for a mean of 11 years and followed a mean of 24 years. A more recent examination of 2384 manufacturing workers, employed between 1952 and 1982, with exposure to a number of pesticides including aldrin found no excess mortality rates attributable to occupational exposures. Similarly, a 2 3-year follow-up of 570 aldrin- and dieldrin-exposed workers found no increase in overall mortality rates or mortality from liver cancer."... 

Exposure of rats and beagle dogs to 12 ppm for 6 hours/day, 5 days/weekfor 13 weeks produced severe testicular damage and slight hypoplasia of the spleen, thymus, lymph nodes, and bone marrow." In the rats both immature and mature spermatids no longer appeared in the seminiferous tubules no spermatozoa were noted in the epididymal tubules. Normal spermatogenesis was only partly restored at 84 days after exposure. Similar exposure at 0.1 ppm caused no effects. 

Lead exposure can produce a number of other effects. One of the most common effects is on the red blood cells, which results in anemia. The red blood cells become fragile and hemoglobin synthesis is impaired. Changes in the red blood cells and some enzymatic changes were used as a marker for lead exposure. Similar to other metals, lead adversely affects kidney function, but this is now rare with reductions in occupational exposure. Several studies have demonstrated that elevated lead exposure is related to elevated blood pressure levels, particularly in men. There appears to be a weak association between lead exposure and increased incidence of lung and brain cancer. Lead exposure is a reproductive hazard for both males and females. In males, lead affects sperm count and sperm motility, resulting in decreased offspring. 

Data on toxicity relevant to clinical treatment would be those describing effects that have not been found clinically, cannot be predicted from the pharmacology, and that occurred at exposures similar to or at low multiples of the human exposure. 

The effects of split doses of x rays on the transformation of Syrian hamster embryo cells and C3H lOTl/2 cdls have been studied Borek and Hall (1974) observed that if an x-ray dose of 0.5 or 0.75 Gy (50 or 75 rad) was divided into two fractions separated by 5 hours, more cell transformation was observed than if the same dose was given in a single exposure. Cell killing, on the other hand, decreased with split doses versus single exposures. Similar split-dose studies with C3H lOTl/2 cells have indicated that the observed effect varies with the x-ray dose used At low doses (< 1 Gy < 100 rad) an enhancement in cell transformation is observed with two split doses (Miller and Hall, 1978 ... 

The peaks corresponding to DDE and PCB are not due to the occupational exposure. Similar peaks are observed in samples from non-exposed persons and are due to the global distribution of these compounds. 

A review of Japanese patients found that of the 15 patients who had developed hematological malignancies since 1975, 6 had other risk factors for leukemia, such as Fanconi s syndrome or prior chemotherapy or radiotherapy. The incidence of leukemia in this study was 3 per 100 000, similar to that in the general population of the same age (68). The National Cooperative Growth Study (NCGS—a postmarketing database that includes 19 846 patient-years since the time of growth hormone exposure) similarly reported no increase in the incidence of new leukemia when patients with other risk factors were excluded from the analysis (96). 

The irreversibility of step 1 is indicated by a rapid O2 response to an O2 step decrease irrespective of the time of O2 exposure. Similarly, the rapidity of the CO response to a step decrease of CO from reaction conditions at steady state indicates the irreversibility of step 2. Hertl (6) found that the only product of thermodesorption of C03O4, preexposed to CO, is CO2. 

Passivation often involves the controlled exposure of the catalyst to air at ambient temperature. Rapid exothermic reactions are prevented while forming stable layers which inhibit further rapid reaction upon air exposure. Similar exposure to other passivating reagents would also lead to air stable surface layers on the metallic surfaces. A typical example is the passivation of Ni catalysts which would oxidize catastrophically upon exposure to air, and of highly-dispersed supported Pt catalysts. Many methods or techniques are available ... 

Reproductive Toxicity. No data were located from studies of the reproductive toxicity of HFC-134a in humans. The animal data were sufficient to show that HFC-134a exposures similar to those metered-dose inhalers did not affect fertility and sexual function. Although there was an effect of exposure to... 

Methotrexate solutions (Img/mL) stored in translucent syringes and exposed to intense window-glass-filtered daylight showed more than 10% degradation after eight hours exposure. Similarly, 5 mg/mL solutions had less than 5% degradation after 24 hours exposure (52). 

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