Experimentation exposure

After the critical study and toxic effect have been selected, the USEPA identifies the experimental exposure level representing the highest level tested at which no adverse effects (including the critical toxic effect) were demonstrated. This highest "no-obserx cd-adversc-effcct-lever (NOAEL) is the key datum obtained from the study of the dose-response relationship. A NOAEL obserx ed in an animal study in which the exposure was intermittent (such as five days per week) is adjusted to reflect continuous exposure. 

Experimental exposure of several agricultural crops to ambient levels of acidic pollutants has not established measurable yield responses although foliar damage has been observed. Complex interactions with other airborne pollutants, particularly ozone, makes it difficult to exactly establish the damages that may be attributed to acidic deposition 14), It has not been possible to establish any critical level of acidic deposition in relation to crop damages. 

Experimental exposure studies have attempted to associate various neurological effects in humans with specific trichloroethylene exposure levels. Voluntary exposures of 1 hours resulted in complaints of drowsiness at 27 ppm and headache at 81 ppm (Nomiyama and Nomiyama 1977). These are very low exposure levels, but the results are questionable because of the use of only three test subjects per dose, lack of statistical analysis, sporadic occurrence of the effects, lack of clear dose-response relationships, and discrepancies between the text and summary table in the report. Therefore, this study is not presented in Table 2-1. No effects on visual perception, two-point discrimination, blood pressure, pulse rate, or respiration rate were observed at any vapor concentration in this study. Other neurobehavioral tests were not performed, and the subjects were not evaluated following exposure. 

Nihlen A, R Walindrer, A Lof, G Johanson (1998) Experimental exposure to methyl tertiary-hvAyi ether. II. 

Holm, G., L. Norrgren, and O. Linden. 1991. Reproductive and histopathological effects of long-term experimental exposure to bis(tributyltin)oxide (TBTO) on the three-spined stickleback, Gasterosteus aculeatus Linnaeus. Jour. Fish Biol. 38 373-386. 

De Guise, S., Maratea, J. And Perkins, C., Malathion immunotoxicity in the American lobster Homarus americanus upon experimental exposure, Aquatic Toxicol., 66, 419, 2004. 

Adequate data were available for development of the three AEGL classifications. Inadequate data were available for determination of the relationship between concentration and exposure duration for a fixed effect. However, based on the rapidity with which blood concentrations in humans approached equilibrium, the similarity in lethality values in rats exposed for 4 or 6 hours (h), and the fact that the cardiac sensitization effect is based on a concentration threshold rather than exposure duration, a single AEGL value was used across all time periods for each AEGL classification. Some experimental exposure durations in both human and animal studies were generally long, 4 to 6 h, which lends confidence to using the same value for all exposure durations. 

Experimental exposure in relation to the expected human exposure a default value of 3 for extrapolation from short-term to subchronic exposure a default value of 2-3 for extrapolation from subchronic to chronic exposure... 

The most relevant study to base a hazard assessment and derivation of a tolerable intake upon is a study that reflects the human exposure situation as well as possible. Eor numerous substances, data are only available from acute (single exposure), subacute (14—28 days), or subchronic (90 days) animal studies. In order to derive, e.g., a TDl or RfD for such a substance, it may be necessary to base the assessment on data from a shorter duration study. An assessment factor allowing for differences in the experimental exposure duration and the duration of exposure for the population and scenario under consideration needs to be considered taking into account that, in general, the experimental NOAEL will decrease with increasing exposure duration as well as other and more serious adverse effects may appear with increasing exposure duration. 

Iregren A, Lof A, Tbomingas A, et al Irritation effects from experimental exposure to n-butyl acetate. AmJ Ind Med 24 727-742, 1993... 

Experimental exposure of four human subjects to MIC for 1-5 minutes caused the following effects 0.04ppm, no effects 2 ppm, lacrimation, irritation of the nose and throat 4 ppm, symptoms of irritation more marked 21 ppm, unbearable irritation of eyes, nose, and throat. ... 

Akesson B, Paulsson K Experimental exposure of male volunteers to A/-methyl-2-pyrrolidone (NMP) Acute effects and pharmacokinetics of NMP in plasma and urine. Occup Environ Med 54(4) 2 36-240,1997... 

Jearvinen P, Engstreom K, Riihimeaki V, et al Effects of experimental exposure to triethylamine on vision and the eye. Occup Environ... 

The Department of the Army asked the Committee on Toxicology, In the Board on Toxicology and Environmental Health Hazards of the Commission on Life Sciences, National Research Council (NRC) to conduct a study of the possible chronic adverse health effects on servicemen of experimental exposure to various chemicals at the U.S. Army Laboratories (formerly the Army Chemical Center), Edgewood,... 

After completion of Volume 1, three new panels were established to Identify and assess evidence on the possible long-term health effects or delayed sequelae of the three chemical classes tested. This was done over a period of a year, during which each panel met three times. Pertinent material was examined to evaluate the possibility that experimental exposure of soldiers may have resulted in untoward health effects. The three panels were separately concerned with four cholinesterase reactivator chemicals (oximes) two types of psychochemicals (phencyclidine and dlmethylheptylpyran and congeners), administered In pure form, as opposed to street drugs and mustard gas and several lacrlmatory and respiratory irritants (such as CN, CS, CR, and CA). 

From 1958 to 1973, at least 1,366 human subjects underwent experimental exposures to CS at Edgewood. For 1,073 subjects, there was some type of aerosol CS exposure, 180 subjects had skin applications, 82 subjects had both skin applications and aerosol exposures, and 31 underwent CS applications to their eyes. 

Between 1958 and 1972, 99 human subjects underwent experimental exposures to CN at Edgewood Arsenal. Sixty-nine subjects had aerosol exposures in a chamber that they entered masked they removed the masks after the agent concentration had equilibrated. Thirty subjects had direct skin applications of CN. 

From 1963 to 1972, 97 subjects underwent experimental exposures to CR at Edgewood 33 had aerosol exposures In a chamber, and 64 had cutaneous exposures. 

Sixty-seven human subjects underwent experimental exposure to DM 29 in 1958 and 38 in 1966-1968, of whom exposure data are available on 23 and 31, respectively. Subjects were exposed in an aerosol chamber they wore masks when they entered, and the masks were often removed after some intervals In the chamber. 

In 1966, 13 human subjects underwent experimental exposures to CA at Edgewood. The subjects wore masks when they entered an aerosol chamber and removed the masks after equilibration of the chamber CA concentration. 

From 1955 to 1971, 136 subjects underwent one or two experimental exposures to PS in equipment tests. The subjects remained in a test chamber for up to 4 h with gas masks in place and sometimes simulated battlefield functions. 

In 1958, 32 subjects underwent experimental exposure to nonanoyl morpholide In an aerosol chamber at Edgewood. At least some subjects wore maska during exposure. Exposure data are available on 30 subjects. Subjects had one to four exposures on 1 or 2 d. Exposure durations, available for 15 subjects, ranged from 10 s to 8 min. No Ct s are avllable. 

In late 1969 and early 1970, 16 subjects each underwent one experimental exposure to CHT In an aerosol chamber at Edgewood. The duration of exposure among the 16 subjects ranged from 30 s to 5 min. Ct s ranged from 15.4 to 64 mg min/m. ... 

Falk, H. L., I. Markul, and P. Kotin, Aromatic Hydrocarbons. IV. Their Fate Following Emission into the Atmosphere and Experimental Exposure to Washed Air and Synthetic Smog, Arch. Ind. Health, 13, 13-17 (1956). 

Figure 5.18 shows vascular endothelial growth factor (VEGF) levels in the supernatant rinsing media of the epithelial side in the EVEIT system (SM) of ex vivo corneas after exposure to various concentrations of NaOH. The ordinate shows VEGF levels in percentage of initial values after 36 h of perfusion, i.e., immediately before the experimental exposure. The concentrations of NaOH used in each set of experiments are indicated in the abscissa. Three corneas each were... 

Renal and hepatic toxicity has been described follow ing human accidental poisonings and experimental exposure of rats and mice. In rats, hepatic cytochrome P450 content, particularly of CYP2B1, and the activities of certain conjugation enzymes are increased upon inhalation exposure to meta- y ex Q. Although xylenes have been studied extensively, there is no confirmed evidence of genetic activity for any of the isomers. 

CCL + HCI + excess CH4. The reaclion is carried out in the liquid phase al about 35 C. Ultraviolet light is used as a catalyst. The same reaclion can be carried oul al 475"C without catalyst. The unreacted methane and partially chlorinated products are recycled to control the yield of CCL. Toxicity. The experimental exposure of laboratory animals to the vapors or CCL has shown it to be very toxic by inhalation at concentrations easily obtainable at ambient temperatures, An overexposure to carbon tetrachloride has been known to cause acute but temporary loss of renal function. 

Animals poisoned by chlordane, heptachlor and/or related compounds show very marked loss of appetite and neurologic symptoms. Repeated experimental exposure to low doses of chlordane lead to hyperexcitability, tremors and convulsions, followed by marked anorexia and loss of weight for those animals that survive long enough. Chronic exposure to chlordane or heptachlor leads to degenerative changes in the liver and kidney tubules. 

When sufficient data are available, use of the benchmark dose (BMD) or benchmark concentration (BMC) approach is preferable to the traditional health-based guidance value approaches (IPCS, 1999a, 2005 USEPA, 2000 Sonich-Mullin et al 2001). The BMDL (or BMCL) is the lower confidence limit on a dose (the BMD) (or concentration, BMC) that produces a particular level of response or change from the control mean (e.g. 10% response rate for quantal responses one standard deviation from the control mean for a continuous response) and can be used in place of the NOAEL. The BMD/BMC approach provides several advantages for dose-response evaluation 1) the model fits all of the available data and takes into account the slope of the dose-response curve 2) it accounts for variability in the data and 3) the BMD/BMC is not limited to one experimental exposure level, and the model can extrapolate outside of the experimental range. 

The long-term health effects of most interest included the possibility of excess cancer risk and adverse mental, neurologic, hepatic, and reproductive effects that might have resulted from experimental exposure to chemicals at Edgewood. 

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