Human data case studies

The book begins with a discussion of the theories of error causation and then goes on to describe the various ways in which data can be collected, analyzed, and used to reduce the potential for error. Case studies are used to teach the methodology of error reduction in specific industry operations. Finally, the book concludes with a plan for a plant error reduction program and a discussion of how human factors principles impact on the process safety management system. 

Because most research effort in the human reliability domain has focused on the quantification of error probabilities, a large number of techniques exist. However, a relatively small number of these techniques have actually been applied in practical risk assessments, and even fewer have been used in the CPI. For this reason, in this section only three techniques will be described in detail. More extensive reviews are available from other sources (e.g., Kirwan et al., 1988 Kirwan, 1990 Meister, 1984). Following a brief description of each technique, a case study will be provided to illustrate the application of the technique in practice. As emphasized in the early part of this chapter, quantification has to be preceded by a rigorous qualitative analysis in order to ensure that all errors with significant consequences are identified. If the qualitative analysis is incomplete, then quanhfication will be inaccurate. It is also important to be aware of the limitations of the accuracy of the data generally available... 

The data situation for additives in LCIA seems to be somewhat better than for the LCI [4]. Characterization factors exist for a number of additives and for a number of impact categories. Nevertheless, the fist is nowhere near complete. Especially for the impact categories of human toxicity and ecotoxicity, impact factors are missing. Approaches exist to calculate such factors based on substance characteristics. In this volume, LCIA factors are derived for a large number of additives based on such approaches [5]. The lack of such factors, therefore, seems to be less of a problem for including additives in LCA case studies than the lack of LCI data. 

No conclusion about hematological effects in humans after exposure to chloroform can be made on the basis of one case study in humans. From the experimental data in animals, it is evident that all hematological effects observed in rats were due to oral exposure of acute, intermediate, or chronic duration. It is possible that the hematological effects observed in rats are transient. Human exposure to chloroform in the environment, drinking water, or at hazardous waste sites is likely to cause few or no hematological effects. 

No studies were located regarding death in humans after oral exposure to heptachlor or heptachlor epoxide. However, since heptachlor is a major component of the insecticide chlordane, chlordane poisoning can be considered when evaluating heptachlor toxicity data. In the case study of a woman who ingested 6 g of chlordane with suicidal intent and died 9.5 days following ingestion, no information was presented on the composition of the chlordane. Therefore, the amount of heptachlor exposure is unknown, and the effect of other components of chlordane cannot be ruled out (Derbes et al. 1955). 

Death. Occupational mortality studies of pesticide workers exposed to heptachlor have not revealed an excess number of deaths in these cohorts compared to the general U.S. population. This may possibly be explained as a healthy worker effect. The ERA has described human case reports in which convulsions and death were reported following suicidal ingestion of technical-grade chlordane, which typically contains 6-30% heptachlor, but these effects cannot be attributed to heptachlor or heptachlor epoxide. There are no controlled, quantitative human data for any route of exposure. Acute lethality data were located for animals exposed via the oral and dermal routes. Both heptachlor and heptachlor epoxide may be considered very toxic via the oral route on the basis of acute animal data in rats and mice. Intermediate oral exposure to these compounds also caused up to 40% and 100% mortality in rats and mice, respectively. There appear to be differences in sensitivity in males and females in some species with the males being most sensitive. Heptachlor epoxide is more toxic than heptachlor. Heptachlor may be considered very toxic to extremely toxic via the dermal route on the basis of acute lethality data in rats and mice. The severity of acute effects may possibly depend upon the extent of formation of heptachlor epoxide and the species tested. 

Neurotoxicity. The only human data on neurotoxicity come from case reports of occupational exposures to chlordane in which the route was not specified, and for which the effects could not be related directly to heptachlor or heptachlor epoxide alone (Dadey and Kammer 1953). Signs of neurotoxicity, such as irritability, salivation, lethargy, dizziness, labored respiration, muscle tremors, and convulsions, were reported. No data exist describing neurologic effects in animals following inhalation exposure of any duration. Acute and intermediate oral studies in animals provide support for the supposition that the neurotoxicity of chlordane seen in humans may be due in part to heptachlor or heptachlor epoxide. Although there are no reasons to suspect that neurotoxic effects... 

Deseriptive data are available from reports of humans exposed to 1,4-diehlorobenzene by inhalation (and possibly dermal contact). It is important to note that the case studies discussed in this section should be interpreted with caution since they reflect incidents in which individuals have reportedly been exposed to 1,4-dichlorobenzene, and they assume that there has been no other exposure to potentially toxic or infectious agents. There is usually little or no verification of these assumptions. Case studies in general are not scientifically equivalent to carefiilly designed epidemiological studies or to adequately controlled and monitored laboratory experiments. Thus, the case studies described below should be considered only as providing supplementary evidence that 1,4-dichlorobenzene may cause the reported effects. 

Most of the data described in this section were derived from laboratory studies in which 1,4-dichlorobenzene was administered to test animals via gavage. In addition, two human case studies of... 

Based on a combination of available human case studies and experiments with laboratory animals, the major public health concerns associated with exposure to 1,4-dichlorobenzene are effects on the liver, kidneys, and blood. Some immunological, dermatological, and neurological effects have also been reported in exposed humans. There is information from animal studies which raises the question of whether 1,4-dichlorobenzene can cross the placenta and elicit structural effects on the developing fetus. Data from a study conducted in rats using the intraperitoneal route have demonstrated sperm abnormalities. Cancer of the liver as a result of lifetime exposure to 1,4-dichlorobenzene has been shown in mice, and renal cancer has been reported in male rats. However, recent studies related to the mechanism of renal carcinogenesis in rats suggest that these tumors may not be expected to occur in exposed humans. Issues relevant to children are explicitly discussed in Section 2.6, Children s Susceptibility, and Section 5.6, Exposures of Children. 

Death. There are some data to suggest that lethality may be a public health concern for persons exposed for prolonged periods of time to high levels of 1,4-dichlorobenzene in confined areas (e.g., in homes). The only available information related to the death of humans exposed to 1,4-dichlorobenzene is a case study of a 60-year-old man and his wife who both died of liver ailments after the air in their home had been found to contain increased air concentrations of 1,4-dichlorobenzene (described as saturated ) for 3-4 months (Cotter 1953). However, the exact air concentration of 1,4-dichlorobenzene was not measured or reported, nor was the existence or nature of other possible factors contributing to their deaths (e.g., pattern of alcohol consumption, exposure to other chemicals, or pre-existing medical... 

Hepatic Effects. Liver effects reported in case studies in humans exposed to 1,4-dichlorobenzene via inhalation have included jaundice, cirrhosis, and atrophy (Cotter 1953). Estimates of exposure duration ranged from 1 to 18 months however, quantitative data on 1,4-dichlorobenzene levels were not available. One report was located that described a 3-year-old boy who may have ingested 1,4-dichlorobenzene crystals. Jaundice was reported, indicating that liver function was in some way compromised, although no further details were reported. No dermal exposures to 1,4-dichlorobenzene in humans were reported. The lack of reliable information regarding human exposures to 1,4-dichlorobenzene by all three routes of exposure makes it difficult to draw any helpful conclusions about the toxicity of 1,4-dichlorobenzene in humans. 

Information regarding health effects of fuel oils in humans and animals is available for the inhalation, oral, and dermal routes of exposure. Most of the information in humans is from cases of accidental ingestion of kerosene that resulted in respiratory, neurotoxic, and to a lesser extent, gastrointestinal effects. In addition, a few case studies have identified these effects as well as cardiovascular, hematological, and renal effects in humans after inhalation and/or dermal exposures to fuel oils. Fuel oils appear to be eye and skin irritants in both animals and humans following direct contact. Animal data exist for most systemic effects however, the data are inconclusive for many of the endpoints. Further, a number of the animal studies... 

No information was located regarding the toxicity of fuel oils in susceptible populations. The human data, in general, were based upon case studies that reported ingestion of kerosene by children. Although children were not shown to be particularly susceptible to kerosene in these studies, it was obvious that... 

Human data include information from case reports (e.g., poisonings), clinical examinations, experimental studies in volunteers, experiences from the working environment, epidemiological studies, and meta-analyses. 

Well-documented human data can often provide very useful information on skin and/or respiratory tract irritation, sometimes for a range of exposure levels. Often, the only useful information on respiratory tract irritation, which can be a threshold effect in the workplace, is obtained from human experience. It may in some cases be possible to derive a reliable NOAEL and/or LOAEL from human studies however, usually there is only the information that a substance is irritating or, often by inference only, that it is not. The usefulness of human data on irritation will depend on the extent to which the effect, and its magnitude, can be reliably attributed to the substance under evaluation. Furthermore, there may be a significant level of uncertainty in human data on irritant effects because of poor reporting, lack of specific information on exposure, subjective or anecdotal reporting of effects, small numbers of subjects, etc. 

---