Dose threshold

In this scheme, OELs should be a dose somewhere between compensatory effects, in which the organism is able to detoxify, metabolize, or excrete the substance, and early impairment. Although there may be profound differences of opinion as to what constitutes this dose, this approach leads to the conclusion that available scientific data permits identification of a clear threshold dose below which exposure to the substance in question is not expected to lead to adverse effects. 

Threshold dose A dosage or exposure level below which the adverse effects of a substance are not realized or expressed by the exposed population. 

Although the exact mechanisms of action of LSD and tryptamine-related compounds are incompletely understood (Freedman 1987), there is convincing evidence relating the psychotomimetic effects of these substances to serotonergic transmission in the brain (Davis 1987 Freedman 1987 McCall 1986 Nichols 2004). An antagonism of 5-HT in the rat brain is sufficient to cause a fourfold decrease in the threshold dose ofLSD (Appel and Freedman 1964). 

The threshold dose of MDMA is 30 mg, but the average dose is 80-150 mg, with some users taking in excess of 200 mg. The lethal dose is estimated (from animal data) to be approximately 6,000 mg. On the street, concentrations of MDMA can vary greatly, and tablets may also contain other substances such as methylenedioxyamphetamine (MDA) and methylenedioxy-ethylamphetamine (MDEA) (Sherlock et al. 1999). The presence of these other substances is often associated with emergency presentations because of their narrower therapeutic windows. 

The accurate diagnosis of AIA can be established by oral, inhaled, nasal or intravenous placebo-controlled provocations tests with increasing doses of aspirin [10], There is no reliable in vitro test. Oral challenges are most commonly performed, because the oral route mimics natural exposure and the test does not require special equipment, except simple spirometry. The threshold dose of aspirin which provokes a 20% fall in FEVi (positive reaction) will vary with individual patients, depending... 

A typical dose-response is shown in Fig. 11.1. This assumes that a dose exists which has no effects due to the capacity of the body to reverse minor changes and maintain cellular homeostasis. The threshold dose is normally taken to be the observed experimental NOAEL, but the NOAEL could be lower than the threshold dose. The NOAEL chosen is the one that represents the most sensitive species studied since all international protocols require that the chemical is tested on at least two species (frequently the rat and the mouse). 

Threshold Dose—The minimum absorbed dose that will produce a detectable degree of any given effect. 

A Test of the Linear-No-Threshold Dose-Response Relationship for Radiation Carcinogenesis... 

The principal research goal of our project is to test the linear-no threshold dose-response theory for radon-induced lung cancer. This... 

Inhaled nickel is at least 100 times more toxic than ingested nickel because it is more readily absorbed from the lungs than from the gastrointestinal tract, and death is more often the result of respiratory failure than of nervous system effects. For example, oral ingestion of 0.05 mg Ni/kg BW and inhalation at 0.005 Ni/m3 are equally effective threshold doses in rats (USPHS 1977). 

The lowest value on the response versus dose curve is called the threshold dose. Below this dose the body is able to detoxify and eliminate the agent without any detectable effects. In reality the response is only identically zero when the dose is zero, but for small doses the response is not detectable. 

OSHA has defined its own threshold dose, called a permissible exposure level (PEL). 

A second, more extensive experiment involved oral administration of three daily doses (100 mg/kg) of parachlorophenylalanine (PCPA). This tryptophan hydroxylase inhibitor (47), like reserpine, enhanced the behavioral effects of LSD (13) moreover, hypersensitivity occurred when 5-HT, but not other monoamine, concentrations were below normal in both forebrain and hindbrain (13). That is, effects were observed at 5 and 12 days (when 5-HT was depleted to 10-20% and 60-70% of normal) but not at 21 days (when 5-HT had returned to normal). Control experiments (13) indicated that (a) the interaction of PCPA, 5-HT, and LSD was probably not caused by generalized hyperactivity or hyperirritability sometimes seen after PCPA (73) (b) PCPA does not affect threshold doses of other psychoactive but nonserotonergic compounds, such as d-amphetamine (0.3 mg/kg) and (c) pretreatment with a-methylparatyrosine, a tyrosine hydroxylase inhibitor which depletes catecholamines rather than indoleamines, does not alter sensitivity to LSD. 

Threshold dose, 25 233. See also TD50 estimating, 25 235 Threshold gain, 14 665 Thresholding process, 18 148 Threshold inhibitors, 26 139 Threshold limit values (TLV), 1 819,... 

Stoeger T, Reinhard C, Takenaka S, Schroeppel A, Karg E, Ritter B, Heyder J, Schulz H (2006) Instillation of six different ultrafme carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. Environmental Health Perspectives 114 328-333. 

As has been emphasized so many times in the preceding chapters, these various manifestations of toxicity all display dose-response characteristics, where by response we refer to the incidence or severity of specific adverse health effects. As we demonstrated in earlier chapters, toxic responses increase in incidence, in severity, and sometimes in both, as dose increases. Moreover, just below the range of doses over which adverse effects can be observed, there is usually evidence for a threshold dose, what we have called the no-observed adverse effect level (NOAEL). The threshold dose must be exceeded before adverse effects become observable (Chapter 3). Deriving from the literature on toxic hazards, descriptions of the dose-response relationships for those hazards comprise the dose-response assessment step of the four-step process. 

---