1,4-dichlorobenzene case study

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. 

Only one report of human death attributed to 1,4-dichlorobenzene exposure has been located in the literature. A 60-year-old man and his wife died within months of each other due to acute yellow atrophy of the liver (also known as massive hepatic necrosis or fulminant hepatitis) (Cotter 1953). Their home had been "saturated" with 1,4-dichlorobenzene mothball vapor for a period of about 3-4 months, but no air measurements were available. Clinical symptoms included severe headache, diarrhea, numbness, clumsiness, slurred speech, weight loss (50 pounds in 3 months in the case of the husband), and jaundice. The wife died within a year of the initial exposure however, it was not clear if 1,4-dichlorobenzene was the primary cause of death. This case study did not address whether these individuals consumed excessive amounts of alcohol or had previous medical problems, such as a chronic liver infection. 

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... 

Hepatic Effects. A single case study was located regarding hepatic effects in humans after oral exposure to 1,4-dichlorobenzene. In this case report, the author describes a 3-year-old boy who had been playing with crystals containing 1,4-dichlorobenzene for 4-5 days before being admitted to the hospital. On admission, the boy was jaundiced and his mucous membranes were pale. After a blood transfusion. 

No studies were located regarding immunological effects in humans after oral exposure to 1,4-dichlorobenzene. S5mimetrical lesions with a bizarre pattern of skin pigmentation over most of her body were reported in the case study of a 19-year-old black woman who ingested 4-5 moth pellets of 1,4-dichloro-... 

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. 

Body Weight Effects. Unknown amounts of inhaled 1,4-dichlorobenzene have been reported to cause decreases in body weight in humans (Cotter 1953). Little more significant information was reported in these individual case studies, indicating that other factors may have resulted in the loss of body weight. The human database is insufficient to draw any substantial conclusion about 1,4-dichlorobenzene s ability to cause decreases in body weight. 

Some limited information (i.e., anecdotal, single acute-duration exposure, and workplace exposure) is available on the health effects of human exposure to 1,4-dichlorobenzene via inhalation and the oral route. For persons exposed via inhalation, there is information on death, systemic effects, neurologic effects, or the role of lifestyle factors resulting from intermediate- and chronic-duration exposure. There is also information on systemic effects in humans resulting from acute-, intermediate-, and chronic-duration oral exposure. It is important to note that most of this information was obtained from case studies in which levels and durations of exposure to 1,4-dichlorobenzene were unknown or uncertain. 

As this example with p-dichlorobenzene shows the different levels of OELs are connected to differing scientific opinions on the harmful effects of the substance. The selection of what data to review obviously is important for the outcome of the risk assessment. It can also be concluded to not only being dependent on the time-related availability of the data. The potential for a selection bias of what literature to review in risk assessments has been shown by Ruden for the risk assessments concerning the carcinogenic properties of trichloroethylene (Ruden 2001). Although a case-study of acryl amide (Ruden 2004) shows that a selection bias by no means is an inevitable consequence. Another aspect of which the conclusions from a risk... 

This case study is a reactor-separator-recycle system to produce monochlorobenzene. The operating parameters and sizes for one of the synthesis alternatives are optimised using the detailed models and the costing information provided. Each unit has a capital cost, Cc, and an operating cost, Q, which is incorporated into the objective function through a pay out time of 2.5 years. The principal units are a CSTR and two separation columns. The models have been reformulated in terms of component flowrates, Fsj. The reactor is a continuous stirred tank reactor (CSTR) which models the reaction between chlorine and benzene (A) to produce monochlorobenzene ( B) and dichlorobenzene (C) at a constant temperature. The maximum (global) profit is 2081/day. 

The preceding chapters used brief case studies to illustrate key points. This chapter examines the life cycle of four substances in greater detail. Three of these substances, orthonitrochlorobenzene, 1,4-dichlorobenzene, and hexa-chlorobenzene, share a basic chlorinated benzene structure. The degree of chlorination and the presence of other functional groups affect their properties, usage, fate and transport in the environment, and (eco)toxicity. These substances also differ in their uses, which influences the potential for exposure. The remaining case study examines microbeads, a product whose size determines in part its life cycle. 

These values are currently under review by EPA and have not been included in the IRIS (1998) database. It is not likely, based on the potential for human exposure data presented in Chapter 5, coupled with the NOAELs and LOAELs gathered from human case reports and laboratory animal studies, that levels of 1,4-dichlorobenzene in the drinking water in any location would be high enough to cause a concern for cancer in humans. 

Few studies have reported toxicological effects of 1,4-dichlorobenzene in children. Campbell and Davidson (1970) reported a case of a 21-year-old woman eating 1-2 toilet air-freshener blocks per week while pregnant. The mother developed hematological aberrations (hypochromic, microcytic anemia. 

Developmental Toxicity. No studies have been located that reported developmental effects on the offspring of humans exposed to 1,4-dichlorobenzene via the inhalation, oral, or dermal routes. Only one human case report mentioned the potential developmental effects of ingesting 1,4-dichlorobenzene at 38 weeks of gestation. The mother developed hematological effects due to 1,4-dichlorobenzene consumption, but she did deliver a normal 4.3-kg female infant. Based on this one report, there appears to be little developmental toxicity of 1,4-dichlorobenzene in humans (Campbell and Davidson 1970) however, more information is clearly needed to confirm this observation in humans. 

In a long-term inhalation study in male and female rats and female mice, there was no evidence of carcinogenicity after exposure at 75 or 500 ppm for 5 hours/day, 5 days/weekfor 76 weeks (rats) or 57 weeks (mice). Although there has been a report of five cases of blood dyscrasias, including leukemia, among individuals exposed to o- or p-dichlorobenzene, the lARC has concluded that the human data are inadequate to evaluate the carcinogenicity of dichlorobenzenes but the para-isomer is possibly carcinogenic to humans. ... 

Further chlorination reactions can also take place, but since they involve insignificant amounts of reactants they have been considered to be negligible. The kinetics of the process were studied by McMullin (1948), who showed that the chlorination of benzene (A), monochlorobenzene (B) and dichlorobenzene (C) is in all cases first-order and irreversible. 

---