Human exposure studies

The Guidelines for Developmental Toxicity Risk Assessment (US-EPA 1991) outline principles and methods for evaluating data from animal and human studies, exposure data, and other information to characterize risk to human development, growth, survival, and function because of exposure prior to conception, prenatally, or to infants and children. 

In experimental human studies, exposure to 4500ppm for 30-100 minutes resulted in significant impairment in tests of manual dex-... 

TCDD or 2,3,7,8-TCDD-contaminated chemicals, workers involved in manufacturing or application of phenoxy herbicides and/or chlorophenols, and Vietnam veterans. In most of the human studies, exposure was poorly characterized. 

Hematological Effects. No information was found regarding hematological effects in humans following exposure to methyl parathion. Repeated oral exposure to methyl parathion resulted in decreased mean corpuseular volume in one study and decreased hematocrit and erythrocyte count in another study in rats. Chronic ingestion of methyl parathion induced reduction of mean hemoglobin, hematocrit, and erythrocyte eounts in rats. 

Ongoing remedial investigations and feasibility studies conducted at the NPL sites known to be contaminated with methyl parathion will add to the available database on exposure levels in environmental media, exposure levels in humans, and exposure registries. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-efifect level (NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not meant to support regulatory action but to acquaint health professionals with exposure levels at which adverse health effects are not expected to occur in humans. They should help physicians and public health officials determine the safety of a community living near a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely on toxicological studies in animals and on reports of human occupational exposure. 

No studies were located regarding endocrine disruption in humans after exposure to endosulfan. 

Following dermal exposure, trichloroethylene has been detected in blood and expired breath in human studies (Sato and Nakajima 1978). Studies of distribution among other tissues after dermal exposure in humans and animals were not located in the available literature. 

The degree of confidence in the final estimation of risk depends on variability, uncertainty, and assumptions identified in all previous steps. The nature of the information available for risk characterization and the associated uncertainties can vary widely, and no single approach is suitable for all hazard and exposure scenarios. In cases in which risk characterization is concluded before human exposure occurs, for example, with food additives that require prior approval, both hazard identification and hazard characterization are largely dependent on animal experiments. And exposure is a theoretical estimate based on predicted uses or residue levels. In contrast, in cases of prior human exposure, hazard identification and hazard characterization may be based on studies in humans and exposure assessment can be based on real-life, actual intake measurements. The influence of estimates and assumptions can be evaluated by using sensitivity and uncertainty analyses. - Risk assessment procedures differ in a range of possible options from relatively unso-... 

One common objective of an LSMBS is to refine the estimates of actual exposure of consumers to ingredients or impurities in one or more products. For example, study results might be intended to determine a realistic human dietary exposure to pesticide residues in fresh fruits and vegetables. The advent of the Food Quality Protection Act of 1996 (FQPA) has produced an enhanced focus on the exposure of children to pesticides. A well-designed and implemented LSMBS would afford the opportunity to delineate better the exposure and risk to children and other population subgroups. The LSMBS would provide consumer-level data at or near the point of consumption, allowing the refined, relevant, and realistic assessments of dietary exposure. 

Cancer is the major latent harmful effect produced by ionizing radiation and the one that most people exposed to radiation are concerned about. The ability of alpha, beta, and gamma radiation to produce cancer in virtually every tissue and organ in laboratory animals has been well-demonstrated. The development of cancer is not an immediate effect. In humans, radiation-induced leukemia has the shortest latent period at 2 years, while other radiation induced cancers have latent periods >20 years. The mechanism by which cancer is induced in living cells is complex and is a topic of intense study. Exposure to ionizing radiation can produce cancer at any site within the body however, some sites appear to be more common than others, such as the breast, lung, stomach, and thyroid. 

No studies were located regarding the parent compound as a biomarker of exposure in humans. Animal exposure to diisopropyl methylphosphonate can be determined by measuring the parent compound in urine. However, since less than 3% of the parent compound was excreted in the urine of mice and rats, concentrations of the parent compound may be below detection levels (Hart 1976). No accumulation of the parent compound in tissues was identified. Elimination of diisopropyl methylphosphonate from the body occurs rapidly. Excretion is primarily in the urine as the metabolite IMPA. 

Comparative Toxicokinetics. There are no data on the kinetics of diisopropyl methylphosphonate in humans. Studies in animals suggest that metabolism and urinary metabolite profiles are qualitatively similar among species. Additional studies would be useful in understanding the differences in metabolic rates in species and in determining which animal species is the most appropriate model for human exposure. 

Organophosphate Ester Hydraulic Fluids. No studies were located regarding excretion in humans after dermal exposure to organophosphate ester hydraulic fluids. However, a human study using the tricresyl phosphate isomer tri-orf/w-cresyl phosphate (TOCP) was located. 

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