Cardiovascular toxicity associated with recreational use of diphenylprolinol (diphenyl-2-pyrrolidinemethanol [D2PM]).

INTRODUCTION: Many countries have specific legislation, such as the Controlled Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in the United Kingdom to control recreational drugs. There is a growing market and supply of "novel" recreational drugs that are not covered under appropriate legislation, despite having similar chemical structures and/or clinical effects. In addition, these novel drugs are often sold legally on the street or through the Internet, with limited details of the exact contents, making application of the appropriate legislation difficult. CASE REPORT: A male patient with no risk factors for ischemic heart disease, presented to our emergency department with agitation and chest pain characteristic of ischemia following the ingestion of two units of "Head Candy." He improved with oral diazepam over a period of 12 hours and there was no biochemical evidence of myocardial damage. Serum analysis demonstrated the presence of diphenylprolinol (diphenyl-2-pyrrolidinemethanol [D2PM]) and glaucine at concentrations of 0.17 mg/L and 0.10 mg/L, respectively. No other recreational drugs were detected in an extensive toxicological screen of blood and urine samples. DISCUSSION: This is the first reported case of confirmed toxicity associated with recreational use of diphenylprolinol in combination with glaucine. In our view, this case provides further support for the need for a systematic approach to toxicological screening of patients with recreational drug toxicity to identify emerging drugs and provide evidence for legislative authorities to assist in revising the legal status of recreational drugs.

Acute respiratory distress syndrome and lung fibrosis after ingestion of a high dose of ortho-phenylphenol.

Ortho-phenylphenol (OPP) and its sodium salt are used as fungicides and antibacterial agents, ingestion of which has been found to cause liver toxicity, renal toxicity and carcinomas in the urinary tract of rats. Lung damage due to OPP ingestion has not been reported in humans. We report a suicidal 39-year-old woman with stage II cervical cancer who drank a potentially lethal dose of OPP in the form of a commercial antiseptic, which led to the complication of liver and renal function impairment, severe lung damage with acute respiratory distress syndrome and subsequent severe lung fibrosis. Open lung biopsy showed diffuse alveolar damage. She was discharged after 34 days of hospitalization with continuing domiciliary oxygen therapy.

Workshop on human health impacts of halogenated biphenyls and related compounds.

A workshop on the Human Health Impacts of Halogenated Biphenyls and Related Compounds was held to assess the state of current research on these chemicals and to make recommendations for future studies. Participants discussed results from laboratory animal experiments on PCBs, PBBs, dioxins, and dibenzofurans which demonstrate a common mode of toxicological action while also revealing large variations in toxicological potency both within and between these chemical families. These variations demonstrate the importance of congener-specific analyses in future studies of effects of exposure to these compounds. Results from epidemiological studies of environmentally exposed adult and pediatric populations from the U.S., Japan, and Taiwan and occupationally exposed cohorts from around the world were considered. It was concluded that available evidence did not demonstrate serious adverse effects such as cancer, in exposed adult cohorts but did provide indications of possible neurobehavioral effects in children exposed in utero. In addition, workshop participants described newly developed markers of exposure and techniques for assessing endocrinological, immunological, and neurological effects and suggested these be applied to epidemiological studies of the effects of polyhalogenated compounds. Other recommendations included identification of other cohorts and development of a large registry of exposed individuals; performance of detailed studies of reproductive function and outcomes in exposed populations; and follow up of neurobehavioral effects in offspring of exposed women.

Environmental politics and science: the case of PBB contamination in Michigan.

This article examines how politics and science interacted against a background of uncertainty to shape policy in the case of environmental contamination by polybrominated biphenyls (PBB) in Michigan. In 1973, between 500 and 1,000 pounds of the flame retardant PBB were accidentally shipped and used instead of the dairy feed additive magnesium oxide, resulting in the widespread contamination of animal feeds, animals, and human food products. The contamination was initially perceived as the private trouble of a single farmer. The problem next became a public issue as public and private institutions grappled with questions of illness, safety, and disposal. To gain influence over those institutions, dissatisfied individuals and groups then turned the PBB contamination into a political controversy. The final section of the present article analyzes how science and politics interacted in: the ways bureaucratic organizations defined the three problems of contamination; the role political controversy played in redefining problems and influencing policy; and the political roles of scientists in controversies over environmental contamination.

Problemas residuales por policlorados aromaticos / Residual problems caused by aromatic polychlorinated compounds

El problema de la contaminacion ambiental a traves del grupo de los bifenilos policlorados senala la necesidad de reglamentar su uso a traves de medidas estatales nacionales como internacionales. La solucion de la problematica del PCB se puede llevar a cabo a traves de la substitucion o de su limitado empleo en la produccion social. Los compuestos utilizados y sus limites de tolerancia en Colombia son ligeramente cubiertos por nuestra legislacion. Para la seguridad de los alimentos se hace imprescindible la determinacion de los valores limites para los PCB

Toxicosis in sows and their pigs caused by feeding rations containing polybrominated biphenyls to sows during pregnancy and lactation.

The toxicity and the distribution of polybrominated biphenyls (PBB) were investigated by feeding rations containing different concentrations of PBB to sows during pregnancy and lactation. Sows and newborn pigs were clinically unaffected. Mortality was increased among pigs nursing sows fed rations containing PBB. Although transplacental passage of PBB resulted in an appreciable amount of PBB in tissues of newborn pigs, far more PBB were transferred to the pigs through the milk. On a body-weight basis, nursing pigs consumed PBB in concentrations similar to the concentrations given to the sows. The highest tissue concentrations of PBB (fat basis) were found in the liver, followed by the adipose tissue, kidney, and brain. Dietary concentrations of 10 mg of PBB/kg of feed increased serum concentrations of alkaline phosphatase, alanine aminotransferase, and thyroid hormones of pigs, whereas dietary concentrations of 100 or 200 mg of PBB/kg of feed caused those values to decrease. Gross pathologic changes consisted of increased weight of the thyroid gland of newborn pigs and increased weight of the liver of 4-week-old pigs. Histologically, thyroid glands of newborn pigs were slightly hyperplastic, and the colloid was scant and vacuolated. In the liver, lesions consisted of fatty change and centrolobular necrosis; changes were more severe in the sows than in the pigs nursing those sows. Measuring serum concentrations of ornithine carbamoyltransferase was the most effective clinical test in assessing the degree of liver damage in the pigs.

New aspects of the origin of hepatocellular vacuoles. An ultrastructural study on rat and mice liver after different intoxications.

The stages of vacuolar formations in liver parenchymal cells of rats and mice following application of phalloidine, amanitine, o-phenylphenol, hexachlorophene and p-chloro-m-cresol were demonstrated by electron microscopic investigations. After treatment the intercellular spaces are markedly widened and in restricted regions exhibit large sacculi penetrating into the cytoplasm of adjacent hepatocytes. In cross-sections these invaginations frequently appear as intracellular vacuoles. Our present investigations, however, clearly demonstrate that these vacuoles are still in direct connection with the intercellular space. The vacuolar formation is more pronounced in older animals and it is suggested that an increased patho-physiological portal hypertension leads to the swelling of the intercellular space.

Immunologic dysfunction among PBB-exposed Michigan dairy farmers.

In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.

Comparison of findings among residents on Michigan dairy farms and consumers of produce purchased from these farms.

Consumers who had purchased farm products from both quarantined and nonquarantined farms were examined during the cross-sectional clinical survey of 1,029 Michigan residents. Since PBB had inadvertently contaminated cattle and other farm animals, ingestion of meat, milk, eggs and other farm products was thought to have possibly resulted in significant PBB body burdens in some consumers. Findings were considered in comparison with those made among farm residents. Prevalence of symptoms in consumers of farm products from quarantined farms (CQ) was similar to that found in farmers on quarantined farms (FQ); the prevalence was lower in consumers of products from nonquarantined farms (CNQ). Liver function abnormalities were found with similar prevalence in dairy farmers and consumers. Distribution, mean and median values of PBB serum levels in consumers were found to be similar to those of dairy farmers. These results indicate that significant body burdens of PBB had been accumulated by some consumers of farm products in Michigan and that prevalence of symptoms and liver function abnormalities resembled those found among dairy farm residents.

Investigation of the health status of Michigan chemical corporation employees.

Clinical findings are reported for a group of 55 employees of the Michigan Chemical Corporation which manufactured FireMaster BP-6 from 1970 to 1974, in addition to a variety of other halogenated fire retardant chemicals. The results are compared with those from a group of male farm residents and consumers from Michigan examined at the same time. An increased prevalence of chest and skin symptoms was observed, compared with farmers. Skin symptoms were more prevalent among former PBB production personnel. Musculosketal symptoms were less prevalent among these workers than among farmers. Serum PBB concentrations are signicantly higher than among farmers. Blood chemistry results were similar for workers and farmers. However, both groups exhibited a significantly higher prevalence of elevated liver function tests (SGOT, SPGT) than a control population of nonexposed farmers. Both farmers and chemical workers showed an association of elevated CEA with serum PBB greater than 10 ppb.

Comparative neurobehavioral study of a polybrominated biphenyl-exposed population in Michigan and a nonexposed group in Wisconsin.

An analysis of findings regarding the prevalence and time course of symptoms and the results of neurobehavioral testing among Michigan and Wisconsin dairy farmers, is reported. Reviewed are: (1) differences in the prevalence of neurological symptoms at the time of examination; (2) differences in the incidence and time course of symptoms for the period 1972--1976; (3) differences among populations and subgroups (sex and age) regarding performance test scores; (4) correlations between performance test scores and neurological symptoms; and (5) correlations between serum PBB levels as indicators of exposure and performance tests and neurological symptoms.

Unanticipated prevalence of symptoms among dairy farmers in Michigan and Wisconsin.

Adverse human health effects resulting from exposure to polychlorinated biphenyls (PBBs) were unknown until the accidental contamination of Michigan dairy farm animal feed in 1973-1974. Human exposure resulted from the consumption of contaminated meat, milk, dairy products, and eggs. In November 1976, the Environmental Sciences Laboratory conducted comprehensive examinations of 933 farmers and residents in Mighigan who were likely to have consumed farm products contaminated with PBB. A comparison group of 229 Wisconsin dairy farmers were examined in March 1977 and the same scientific and medical staffs that conducted the Michigan survey were responsible and the same procedures used. A complete history of symptomatology by organ system, including year of first onset, duration, frequency, and severity of each symptom was obtained by a physician on all adults examined. Statistical analysis of the prevalence of symptoms at the time of examination or during the preceding year in the Michigan and Wisconsin populations studied found the Michigan group to have a significantly higher prevalence of skin, neurological and musculoskeletal symptoms. The increase was seen among the younger age groups 16-35 and 36-55. Michigan females had a higher prevalence of neurological symptoms than the Michigan males. The existing differences could not be explained without considering an etiologic role for exposure to PBB.

Pediatric health aspects of PBBs.

Many Michigan farm children are viewed as having suffered a deterioration in health coincident with contamination of dairy cattle by PBBs. Among Wisconsin dairy farm children such a deterioration was a rare event. There is a suggestion that Michigan farm children who had multiple symptoms during the 1973-76 period are getting better. A discrete syndrome of ill health has not been identified among Michigan farm children. The symptoms complained of indicate a disruption of various physiological functions, including neurobehavioral, gastrointestinal and immunological. Children from quarantined farms do not have a higher prevalence of multiple symptoms than those from nonquarantined farms.

Liver function tests among Michigan and Wisconsin dairy farmers.

Serum activity of SGOT, SGPT, LDH, and alkaline phosphatase was measured in 614 Michigan adults exposed to PBB and 141 Wisconsin adults not so exposed. The Michigan group had higher prevalence of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.005). A clear sex difference was observed. Michigan men had a higher prevalence of abnormal SGPT (p less than 0.005) and LDH (p less than 0.005) than Michigan women, and a higher prevalence than Wisconsin men of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.01). These differences could not be ascribed to differing patterns of alcohol consumption, laboratory error, or choice of criteria for normality/abnormality. Seven Michigan subgroups were defined on the basis of the criteria by which they had been selected to participate. The two subgroups who were essentially self-invited did not differ from the remaining five randomly selected subgroups combined in prevalence of these abnormal liver function tests. Based on 364 serum PBB analyses thus far analyzed of the 614 Michigan participants, no obvious relationship between serum PBB values and liver function tests was observed. However, this is a tentative conclusion that will be further evaluated when remaining serum PBB analyses are completed. The greater prevalence of abnormal SGPT and SGOT among Michigan dairy farm residents compared to the Wisconsin dairy farm residents is tentatively ascribed to the former group's exposure to PBB.