Previously unknown exposure

In 2006 the EPA said in guidance that reports of previously unknown human exposure to a chemical known or suspected to cause serious adverse effects must be reported  

The discovery of previously unknown and significant human exposure to a chemical, when combined with knowledge that the subject chemical is recognized or suspected as being capable of causing serious adverse health effects (e.g., cancer, birth defects, neurotoxicity), provides a sufficient basis to require the reporting of the new-foimd exposure data to EPA imder section 8(e). 

Discovery of previously unknown presence of a hazardous or toxic chemical in a product is reportable if widespread or significant exposure is substantially likely to occur and presents a substantial risk of injury to health 

The EPA s position on reportability of environmental effects has undergone two upheavals. The EPA s original guidance about environmental effects in 

See infra discussion of the EPAs 8(e) enforcement action against DuPont for an example of EPA allegations concerning failure to report the discovery of substances in human blood suspected of causing adverse effects. 

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Chapter 7 Reporting and Recordkeeping L Previously Unknown Exposure... 

The discussion and studies cited previously generally reflect overall tissue distribution of total arsenic after acute exposure in the case of laboratory animals or unknown exposures in the case of humans. Advances in analytical technology in the last decade have facilitated the identification of tissue-specific patterns of metabolite distribution and accumulation in laboratory animals. Kenyon, Del Razo and Hughes (2005a) found that inorganic arsenic was the predominant form of arsenic in the liver and kidney up to two hours post administration of 10 or 100 p mol As kg-1 as inorganic As(V) to female mice, whereas... 

Under harsher conditions (120 °C in toluene) phosphaalkynes 209 exhibit an analogous reactivity toward elemental tellurium. The previously unknown 1,2,4-telluradiphospholes 74, 304, and 305 were obtained in 15-20% yield along with oligomers of the phosphaalkynes (Equation 42). 1,2,4-Telluradiphospholes 74, 304, and 305 are thermally labile and decompose on exposure to light with deposition of elemental tellurium. 

DNOC is rapidly absorbed by the respiratory tract in humans and animals. A serum DNOC concentration of 1,000 pg/mL was detected in a spray operator 24-36 hours after inhaling a dense DNOC mist for an acute duration (van Noort et al. 1960). The worker subsequently died. Because the spray operator had previous dermal exposure to DNOC, the acute inhalation of dense DNOC mist probably caused the serum DNOC level to spike to lethal levels. A blood DNOC concentration of 60 pg/g was detected in a spray operator who had periodically inhaled an unknown amount of DNOC for 5 weeks (Pollard and Filbee 1951). The blood sample was collected after a 2-day period of no exposure. In addition, a DNOC peak urinary level of 22 mg was detected on the third day after the patient was admitted to the hospital, and a total of 89.9 mg DNOC was eliminated in the urine over 20 days. While these data indicate absorption after inhalation exposure, there was also possible dermal absorption. In an occupational exposure study involving DNOC manufacturers, winter-washer sprayers, and cereal-crop sprayers, a correlation between blood DNOC levels and the symptoms and signs of poisoning was observed (Bidstrup et al. 1952). Blood DNOC levels <10-20 p g/g were not generally associated with signs of toxicity, while concentrations greater than 44 pg/g resulted in several illnesses. 

Since Friedrich Wohler first synthesized urea in 1828, it is estimated that more than 1 million chemicals that were previously unknown in our environment have been synthesized. There are more than 80,000 chemicals manufactured and imported into the United States each year. People are exposed to most of these by air pollution, water pollution, foods and food chain transfers, soil contamination, household use of chemical products, the use of personal care and pharmaceutical products, and industrial contact. Exposure begins before birth in utero and continues throughout life. The different modes of exposure are dealt with separately in the following chapters. 

The authors were unable to find any other similar case report in the literature. TDI is a known respiratory irritant and sensitizer, but is not known to attack the CNS in low concentrations [129, 130]. The low-level exposures to the other solvents could also not account for the observed neurotoxic effects. Clearly, this painter was exposed to a mixture of several hpophiles and hydrophiles that produced this previously unknown effect. 

Sublethal endocrine disruption effects that can occur in the environment at low levels remind us that we still know relatively little about the overall effects of chemicals introduced into our environment. As we have seen, there are over fifty thousand chemicals in use today around the world. We have toxicological data on only about two thousand of these. It is unreasonable to assume that we have identified all of the toxic chemicals in use today, and the levels at which they are toxic to humans. Considering that chemicals can interact with each other in the environment and in the body—either increasing or decreasing the toxicity of each individual chemical—it is almost impossible to predict exactly what will happen from cmy specific chemical exposure. We find new chemicals every day, and mamy of these have specific and previously unknown toxicological mechanisms and effects. 

The Ulsan carbonates (Fig. 1) have long been interpreted as limestone of Paleozoic age or "age unknown" and as the host of a skarn-type iron (magnetite) deposit due to the intrusion of Cretaceous granitic rocks (Park Park 1980 Choi et al. 1999). However, a Paleozoic marine limestone hypothesis fails to explain the spatial association or the relationship between carbonate and ultramafic rocks in a concentric, ellipsoidal shape surrounded by Cretaceous sedimentary, volcanic, and granitic rocks. The sedimentary hypothesis also fails to explain the isolated exposure of a funnel-shaped Paleozoic marine limestone where no marine limestone has been previously observed within the Mesozoic Kyongsang Basin. 

The exact mechanism by which chemical exposures cause MCS is unknown. It is believed that a two-step process occurs. First, an initial exposure or chronic exposures interacts with a susceptible individual, leading to loss of that person s prior, natural tolerance for everyday, low-level chemicals, as well as certain foods, drugs, alcohol, and caffeine. In the second stage, symptoms are thereafter triggered by extremely low doses of previously tolerated products and exposures.2 This theory is called toxicant-induced loss of tolerance or TILT. 3... 

Hattori et al. ]982 Puhl and Fredrickson 1975 Yashiki et al. 1990). Because disulfoton is quickly metabolized, it is rarely detected in the blood or plasma of exposed individuals, but detection of the insecticide in blood provides conclusive evidence of previous exposure. At -2-3 hours after a man accidentally ingested disulfoton, 0.093 nmol/g (4.92 ng/g) of disulfoton and 4.92 nmol/g of total metabolites were detected in his blood (Yashiki et al. 1990). In another study, 1.45 nmol/g of disulfoton was detected in the blood of a man found dead at least 24 hours after he had ingested disulfoton (Hattori et al. 1982). In both cases, the original dose was unknown therefore, a correlation between disulfoton exposure and blood concentration cannot be made. 

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