Exposure information

In the absenee of site-speeifie exposure information, the seleetion of PPE at these sites did not appear to be based on the performanee eharaeteristies of the PPE relative to the hazards and potential hazards. 

Although a number of studies have reported the effects of inhalation exposure to methyl parathion in humans, no inhalation MRLs were derived based on human data because of the lack of adequate quantitative exposure information. Animal data were also insufficient to support the derivation of an acute-, intermediate-, or chronic-duration inhalation MRL. 

In the case of food chemicals, where there is likely to be significant exposure, information is invariably required about the mechanism of action that results in the toxicity. This involves a large amount of extra effort to determine if the effects observed are due to the utilisation of high doses only, or whether or not the mechanisms are likely to occur in humans. 

Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

No animal or human data were available for inhalation exposure. There are no data regarding effects in humans after oral exposure. Information is available in animals regarding health effects following acute, intermediate, and chronic oral ingestion of diisopropyl methylphosphonate. The animal data obtained after oral exposure indicate that diisopropyl methylphosphonate is moderately toxic after acute bolus exposure but has a lower order of toxicity after intermediate and chronic exposures in food. No data were found on the toxicity of diisopropyl methylphosphonate after exposure in drinking water. Further, diisopropyl methylphosphonate is rapidly metabolized and excreted and does not accumulate. It does not appear to have reproductive or developmental effects. At the doses tested, it does not appear to be an acetylcholinesterase inhibitor, although this issue has not been resolved yet. Limited data are available for dermal exposure in humans and animals. Diisopropyl methylphosphonate does not appear to be a... 

Mineral Oil Hydraulic Fluids. There is limited information on the toxicity of mineral oil hydraulic fluids in humans. A single case report of a child accidentally ingesting a single dose of automotive transmission fluid provides limited information on death and systemic effects. A case-control study provides some information on the carcinogenicity of mineral oil hydraulic fluids. The study population was exposed via inhalation and dermal routes. An occupational exposure study provides information on neurotoxicity following chronic dermal exposure. Information on the toxicity of mineral oil hydraulic fluids is limited to a series of inhalation, oral, and dermal acute-duration exposures. These studies provide information on death, systemic effects, and neurotoxicity by inhalation, oral, and dermal routes, and immunotoxicity following dermal exposure. 

The only information that provided an assessment of exposure of children and adolescents to hydrogen sulfide was that developed during the South Karelia Air Pollution Study (Mortilla et al. 1994b) however, these exposures were complicated by simultaneous exposure to other sulfur-containing compounds as well as particulates. Additional exposure information is needed from communities where only hydrogen sulfide exceeds background levels. 

ATSDR s specific responsibilities related to blood lead screening at lead-contaminated hazardous waste sites include (1) evaluation of site-specific environmental lead exposure information, (2) identification of populations potentially exposed to lead, (3) decision about whether or not to conduct blood lead screening, (4) evaluation of blood lead screening results, and (5) determination of whether the U.S. Environmental Protection Agency s (EPA) proposed site remediation plans are sufficient to protect public health. 

Acute-Duration Exposure. Information is available regarding the effects of acute-duration inhalation exposure of humans to acrylonitrile and the effects are characteristic of cyanide-type toxicity. Quantitative data are limited but are sufficient to derive an acute inhalation MRL. Further studies of humans exposed to low levels of acrylonitrile in the workplace would increase the confidence of the acute MRL. Studies in animals support and confirm these findings. No studies are available on the effects of acute-duration oral exposure in humans however, exposure to acrylonitrile reveals neurological disturbances characteristic of cyanide-type toxicity and lethal effects in rats and mice. Rats also develop birth defects. Animal data are sufficient to derive an acute oral MRL. Additional studies employing other species and various dose levels would be useful in confirming target tissues and determining thresholds for these effects. In humans, acrylonitrile causes irritation of the skin and eyes. No data are available on acute dermal exposures in animals. 

HCN is among the most rapidly acting of all known poisons. Absorption occurs by all routes the mechanism of action is inhibition of cellular respiration. The respiratory, central nervous, and cardiovascular systems are the primary targets of an acute exposure. Information on human exposures was limited to exposures to high concentrations for short time intervals, poorly documented accidental exposures, and chronic occupational exposures. 

Effect of Dose and Duration of Exposure on Toxicity. No studies were located where -hexane concentration was measured in workplace air before workers became ill, so no dose-response relationship can be defined for human neurotoxicity as the result of -hexane exposure. Information on duration of exposure leading to toxicity is available from some case series reports. An occupational exposure caused sensory disturbances in the lower extremities after approximately 2 months (Herskowitz et al. 1971). A case of peripheral neuropathy after 7 months of exposure was reported among press-proofing workers in Taipei (Wang et al. 1986) a serious case resulting in quadriplegia after 8 months of exposure was reported among sandal workers in Japan (Yamamura 1969). Based on case reports, it can be estimated... 

Article 6(1) of the Sixth Amendment requires PMN s to contain information and data necessary for evaluating the potential risks of new substances to humans and the environment. This specifically includes certain exposure information listed in Annex VII, concerning proposed uses and estimated yearly production volumes (in ranges, and broken down by use categories). Further, Article 6(1) requires submission of "a declaration concerning the unfavourable effects of the substance in terms of the various uses envisaged," which appears to require statements of the risks that may be associated with the use categories provided under Annex VII.(26)... 

Upon receipt of a PMN, EPA has little direct recourse for requiring a company to develop and otherwise provide more production and use information. Section 5(e) is EPA s major legal authority for obtaining additional information, and that section focuses upon health and environmental effects data, rather than exposure information. 

Not finalized. Proposed rule issued which would require submission of general exposure information for 2300 chemicals (45FR13646). 

If exposure information is available, what was learned from processing this data ... 

A chronic oral MRL was not derived because of the limitations of the available studies. Human studies that described dietary exposure to cyanide through consumption of cassava lacked quantitative exposure information. The one available chronic oral study in rats found no treatment related effects (Howard and Hanzel 1955). 

No studies were located regarding the toxicokinetics of di-/ -octylphthalate in humans or animals following inhalation or dermal exposure. Information on the toxicokinetics of 6i-n-octylphthalate in humans following oral exposure is not available. There are studies that provide indirect evidence for the oral absorption of di- -octylphthalate in animals (Albro and Moore 1974 Oishi 1990 Poon et al. 1995) however, quantitative information is lacking on the rate and extent of absorption following oral exposure to di- -octylphthalate. Information on the distribution of di-w-octylphthalate is limited to oral studies in rats by Oishi (1990), which reported the identification of mono- -octy lphthalate in blood and testes within 1-24 hours (plasma peak at 3 hours, testes peak at 6 hours) after dosing, and by Poon et al. (1995), which reported di- -octylphthalate... 

Acute-Duration Exposure. Information is not available on the health effects of 1,2-diphenylhydrazine resulting from inhalation exposure in humans or animals. Because 1,2-diphenylhydrazine is a solid with a low vapor pressure at ambient temperatures, it is highly unlikely that inhalation exposure to this chemical in the vapor state would occur (Chapter 5). However, the possibility of inhalation exposure to dusts of 1,2- diphenylhydrazine either free or adsorbed to soil is conceivable. Therefore, acute studies of inhalation exposure to dusts of 1,2- diphenylhydrazine could be designed to provide information on possible toxic effects and exposure levels that cause effects. No studies were located regarding acute oral exposure in humans. The only pertinent acute exposure toxicity studies of... 

Several chlorophenols, including 2,5-dichlorophenol, have been identified in laboratory animals exposed to lindane. This indicates that the presence of 2,5-dichlorophenol is fairly specific, but not completely specific, for 1,4-dichlorobenzene exposure. Information on the analytical methods commonly used to detect and quantify 1,4-dichlorobenzene in biological samples is presented in Section 6.1. There are currently no data available to assess a potential correlation between the values obtained with these measurements and the toxic effects observed in humans or laboratory animal species. 

When a full SIDS Dossier on a chemical is available, an initial assessment of the information is undertaken and conclusions are drawn on the potential hazard(s) posed by the chemical and recommendations are made on the need for further work. The conclusions present a summary of the hazards of the chemical, written with sufficient detail and clarity as to be informative and to assist countries with classihcation work and other hazard-based national decision making and exposure information to put the hazard information into context (e.g., on use in the Sponsor country). The recommendation, based on these conclusions, can be either that the chemical is currently of low priority for further work or that it is a candidate for further work to clarify its potential risk (e.g., that further information is required to clarify concerns identified in the SIDS process, and that post-SIDS testing is recommended). 

Work undertaken on a chemical in the OECD HPV Chemicals Program as a follow-up to conclusions and recommendations by SIAM is considered as post-SIDS work, see also Table 2.2. This can include national/regional exposure information gathering and assessment as well as testing of endpoints beyond SIDS to assess a concern identified by SIAM. The Task Force on Existing Chemicals monitors post-SIDS work and can take decisions related to further work to be carried out in OECD in a concerted manner. 

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