Subchronic oral toxicity in guinea pigs of soot from a polychlorinated biphenyl-containing transformer fire

DeCaprio, Anthony P.; McMartin, Donald N.; Silkworth, Jay B.; Rej, Robert; Pause, Ronald; Kaminsky, Laurence S.

doi:10.1016/0041-008x(83)90015-7

Cited by 12 publications

(5 citation statements)

References 21 publications

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“…The influence of the soot matrix was determined by comparing the toxicity of the soot with that of its organic solvent extract, which contained no soot matrix (10). The experimental protocols for acute and subchronic studies of soot toxicity have been described in detail previously (10,11).…”

Section: Toxicologic Assessment Of Sootmentioning

confidence: 99%

Chemical and biological investigations of a transformer accident at Binghamton, NY

O’Keefe¹,

Silkworth²,

Gierthy³

et al. 1985

Environ Health Perspect

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A transformer fire occurred in a state office building in Binghamton, NY on February 5, 1981. Particulates from inside surfaces of ceiling panels on 16 of the 17 floors had concentrations of polychlorinated dibenzofurans (PCDFs) ranging from < 1 part per million (ppm) to 1200 ppm while polychlorinated biphenyl (PCB) concentrations varied from 28 ppm to 23,000 ppm. In spite of the wide variations in contaminant concentrations, complete analytical data from 11 floors showed that there was a consistent PCDF/PCB ratio (0.067 ± 0.026) and also consistent PCDF isomer group distributions (tetra-CDFs, 33 ± 5%; penta-CDFs, 40 ± 3%; hexa-CDFs, 18 ± 7%; hepta-CDFs, 6 ± 3%). It was found that the particulate samples could be successfully ranked in order of their degree of chemical contamination by an in vitro bioassay. The bioassay was based on induction of keratinization or changes in morphology in mouse epithelial cells. Animal toxicology experiments were carried out with a soot sample containing a PCDF concentration which approximated the mean value found on the ceiling particulates. The single dose oral LD values of the soot and its benzene extract equivalent, each administered to female guinea pigs in 0.75% methyl cellulose, were 410 and 327 mg/kg, respectively. These results demonstrated that the soot matrix had virtually no effect on the toxicity of the chemical contaminants in the soot. Morphological alterations in liver tissues from animals receiving the soot were found after examination by electron and light microscopy. Rabbits dermally exposed to the soot and its benzene extract at 500 mg/kg showed evidence of hypertrophy of centrilobular hepatocytes. In addition the rabbits exposed to the soot extract had a local inflammatory reaction at the site of application. In a subchronic feeding experiment carried out for 90 days with guinea pigs, the lowest effect level was found with an accumulated dose of 1.2 mg soot/kg. The observed effects included salivary gland duct metaplasia and decreased relative thymus weights. Based on the chemical analysis data and literature LD values for the more toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and PCDFs, it was calculated that the soot contained the equivalent of 44 ppm 2,3,7,8-tetra-CDD in terms of toxicity to guinea pigs. This was in close agreement with the value of 58 ppm derived from the acute oral toxicity experiments. Air sampling, accomplished on 8 floors in the final stages of the building cleanup, showed maximum total PCDF and 2,3,7,8-tetra-CDF concentrations of 264 and 23 pg/m, respectively. ImagesFIGURE 3.FIGURE 4.FIGURE 5.

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Section: Toxicologic Assessment Of Sootmentioning

confidence: 99%

Chemical and biological investigations of a transformer accident at Binghamton, NY

O’Keefe¹,

Silkworth²,

Gierthy³

et al. 1985

Environ Health Perspect

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“…This was compared with corresponding calculations from the soot study to yield an equivalent concentration (ppm) by using Equation 1. Table 4 summarizes the results of calculations of the 2,3,7,8-TCDD equivalent concentration of Binghamton soot based on dose-response data from previous investigations (34,35 …”

Section: Calculation Of 2378-tcdd Equivalents From Biological Datamentioning

confidence: 99%

“…Thus, Binghamton soot was incorporated into feed at concentrations of 0, 0.2, 1.9, 9.3, 46.3, and 231.5 ppm and fed to guinea pigs for 90 days (34). In another study, 2,3,7,8-TCDD was incorporated into feed at concentrations of 0, 2, 10, 76, and 431 ppt and similarly fed to guinea pigs for purposes of comparison (35).…”

Section: Calculation Of 2378-tcdd Equivalents From Biological Datamentioning

confidence: 99%

“…In this case, use was made of the ED50 (dose level in feed expected to produce a 50% incidence) in order to facilitate comparison of pure 2,3,7,8-TCDD with the Binghamton soot. The ED50 following 90-day exposure to the soot was calculated using previously reported incidence data (39) by a modification of the method of Bliss (36) Finally, an effective LD50 value for prolonged 2,3,7,8-TCDD exposure was similarly derived by using total dose versus mortality data from a recovery experiment in the previous investigation (34). This was compared with corresponding calculations from the soot study to yield an equivalent concentration (ppm) by using Equation 1.…”

Section: Calculation Of 2378-tcdd Equivalents From Biological Datamentioning

confidence: 99%

“…Female guinea pigs were administered a single oral dose of a benzene extract of the soot equivalent to 4, 20, 100, 500, or 1000 mg of soot/kg (24). The soot extract's LD50 was determined to be 327 mg/kg, based on a 42-day observation period and calculated by a modification of the method of Bliss (34). For purposes of comparison, female guinea pigs were similarly given single oral doses of 0.1, 0.5, (1) LDw for soot (mg/kg) it can be calculated that the soot has a 2,3,7,8-TCDD equivalent concentration of (19 Rg/kg)/(327 x 103) ,ug or 58 ppm.…”

Section: Calculation Of 2378-tcdd Equivalents From Biological Datamentioning

confidence: 99%

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Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures

Eadon¹,

Kaminsky²,

Silkworth³

et al. 1986

Environ Health Perspect

112

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Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo- p -dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the “2,3,7,8-TCDD equivalent” concentration of a mixture in order to “predict” its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds.

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Dioxins and the ah receptor

Silbergeld

Gasiewicz

1989

American J Industrial Med

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Despite continuing controversies related to public policy, information on the molecular biology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has advanced significantly over the past decade. Current understanding of the biological mechanisms of TCDD action is based upon the interactions of TCDD with a genetically expressed cytosolic macromolecule that functions as a receptor in many cells across many species. The Ah receptor recognizes TCDD and structurally similar molecules and serves as the transducing step whereby TCDD alters gene expression through the association of the TCDD:receptor complex with specific TCDD-responsive elements on the genome. Understanding these molecular events and their relevance to the organ-level manifestations of TCDD toxicity may be critical to formulating scientifically based assessments of the risk of TCDD exposure.

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Subchronic oral toxicity in guinea pigs of soot from a polychlorinated biphenyl-containing transformer fire

Cited by 12 publications

References 21 publications

Chemical and biological investigations of a transformer accident at Binghamton, NY

Chemical and biological investigations of a transformer accident at Binghamton, NY

Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures

Dioxins and the ah receptor

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