Maximum tolerable exposure

EC Enzyme classification number or MTEL Maximum tolerable exposure level... 

The tentative tolerable daily intakes proposed for certain metals provide a guideline for maximum tolerable exposure. In the case of essential elements, these levels exceed the daily requirements, but this should not be construed as an indication of any change in the recommended daily requirements. In the case of both essential and nonessential metals, the tentative tolerable intake reflects permissible human exposures to these substances as a result of natural occurrence in foods or various food processing practices, as well as exposure from drinking water. 

Concentrations of 1300 ppm to 2000 ppm are lethal on brief exposure of about 1 minute. Concentrations in the range of 1000 ppm to 1300 ppm are dangerous if breathed for 30 minutes. The maximum tolerable concentration for exposure of 1 hour is in the range of 50 ppm. The maximum tolerable exposure for several hours duration is approximately 10 ppm. 

To estimate a maximum tolerated concentration following a 6-h exposure, groups of five male and five female Crl CD-l(ICR)BR mice were exposed at 9,700, 20,000, 30,000, 41,000, or 80,000 ppm (Vlachos 1988). The mice were observed for clinical signs during exposure and for 2-3 d postexposure. Mice... 

Based on the calculated Maximum Dietary Exposure (MDE) of PAEs, and the Non Observed Adverse Effect Level (NOAEL) calculated from the available toxicology evidence, mainly hepatic, renal changes and reproductive toxicity in animals [88, 89,130-133], and making an uncertainty factor between 100 and 200, the EFSA panel calculated the Tolerable Daily Intake (TDI) for DBP, BBP, DEHP,... 

Table 3 Estimation of maximum dietary exposure (MDE) (95th percentile), non observed adverse effect level (NOAEL) and tolerable dally Intake (TDI) of the most used PAEs according to EFSA [62]...

In both mice and rats exposed 6 hours/day 5 days/week for 12 weeks, the no-effect dose was below 150 ppm and the maximum tolerated dose was below 600 ppm. At doses of up to 12 00 ppm there were few signs of overt toxicity, and at necropsy the only treatment related lesions occurred in the liver. Subchronic studies in monkeys showed no exposure-related adverse health effects or reproductive effects after exposure 6 hour/day, 5 days/week for 13 weeks to concentrations of up to 500ppm."... 

McLaughlin, J.E.. Pamo, J., Gamer, F.M., Clary, J.J., Thomas, W.C. Murphy, S.R. (1995) Comparison of the maximum tolerated dose (MTD) dermal response in three strains of mice following repeated exposure to acrylic acid. Food chem. Toxicol., 33, 507-513... 

No studies were found in humans regarding the carcinogenic effect of chlorobenzene via inhalation. Since this is the primary route of environmental exposure, additional studies would be useful to assess potential risk to people who may be exposed to low levels of chlorobenzene in air near hazardous waste sites. There was no evidence for carcinogenicity in both sexes of mice or female rats following oral exposure to chlorobenzene. Since the animals were tested at the maximum tolerated dose and a no-effect level for tumors in rats and mice has been determined, additional oral studies are not warranted at this time. 

At the present time, most US pesticide tolerances were established prior to the passage of FQPA. In assessing consumer risk from exposure to pesticides, the EPA first estimates consumer exposure. The maximum legal exposure to the pesticide is usually first calculated by assuming that... 

This maximum legal exposure, often referred to as the Theoretical Maximum Residue Contribution, or TMRC, is compared with established toxicological criteria such as the reference dose (RfD) or Acceptable Daily Intake (ADI) which represent, after analysis of animal toxicology data and extrapolations to humans, the daily exposure that is not considered to present any appreciable level of risk. When it is determined that the TMRC exposure is below the RfD or ADI, the EPA usually considers the risks from the pesticide in question to be negligible and approves the manufacturer s petition to establish a tolerance at or slightly greater than the maximum levels identified from the manufacturer s controlled field trials (Winter, 1992a). 

In the case of atrazine, the most widely used triazine, refinement of the conservative Tier I estimate for all populations results in at least a 200-fold reduction in exposure and risk. In addition, the total exposure and risk for atrazine using a Tier III approach is approximately 138000-fold to 450000-fold less than the chronic NOAEL obtained from a rodent study. A 600-fold to 1600-fold difference exists between the NOAEL and maximum theoretical exposure and risk when tolerance values are utilized. Further refinement of the estimate using Tier IV methodology would result in even lower exposure and risk, since this Tier III analysis used data generated from structured field trials (maximum label rate and minimum preharvest interval). 

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