Human variability and susceptibility to trichloroethylene.

Pastino, Gina; Yap, W Y; Carroquino, Maria J.

doi:10.1289/ehp.00108s2201

Cited by 30 publications

(34 citation statements)

References 152 publications

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“…Because of its efficacy as a degreasing agent, TCE is used widely by workers for cleaning of metal parts, leading to a high potential for human exposure in occupational environments. Production of TCE increased from about 260,000 pounds in 1982 to 320 million pounds in 1991 (Pastino et al, 2000). The current occupational exposure limit for TCE is 50 ppm (ACGIF, 2002).…”

mentioning

confidence: 99%

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Forkert¹,

Lash²,

Tardif³

et al. 2003

Drug Metab Dispos

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ABSTRACT:We have investigated the potential of the male reproductive tract to accumulate trichloroethylene (TCE) and its metabolites, including chloral, trichloroethanol (TCOH), trichloroacetic acid (TCA), and dichloroacetic acid (DCA). Human seminal fluid and urine samples from eight mechanics diagnosed with clinical infertility and exposed to TCE occupationally were analyzed. In in vivo experimental studies, TCE and its metabolites were determined in epididymis and testis of mice exposed to TCE (1000 ppm) by inhalation for 1 to 4 weeks. In other studies, incubations of monkey epididymal microsomes were performed in the presence of TCE and NADPH. Our results showed that seminal fluid from all eight subjects contained TCE, chloral, and TCOH. DCA was present in samples from two subjects, and only one contained TCA. TCA and/or TCOH were also identified in urine samples from only two subjects. TCE, chloral, and TCOH were detected in murine epididymis after inhalation exposure with TCE for 1 to 4 weeks. Levels of TCE and chloral were similar throughout the entire exposure period. TCOH levels were similar at 1 and 2 weeks but increased significantly after 4 weeks of TCE exposure. Chloral was identified in microsomal incubations with TCE in monkey epididymis. CYP2E1, a P450 that metabolizes TCE, was localized in human and monkey epididymal epithelium and testicular Leydig cells. These results indicated that TCE is metabolized in the reproductive tract of the mouse and monkey. Furthermore, TCE and its metabolites accumulated in seminal fluid, and suggested associations between production of TCE metabolites, reproductive toxicity, and impaired fertility.

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confidence: 99%

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Forkert¹,

Lash²,

Tardif³

et al. 2003

Drug Metab Dispos

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“…However, as is shown in Figure 4 the bioaccumulation potential strongly depends on the biotransformation capacities. This biotransformation capacity is largely chemical-and species-specific and differences in bioaccumulation potential between humans and rodents will arise due to variation in biotransformation rates (Pastino et al 2000).…”

Section: Bioaccumulation Potential Of Air Pollutantsmentioning

confidence: 99%

Bioaccumulation potential of air contaminants: Combining biological allometry, chemical equilibrium and mass-balances to predict accumulation of air pollutants in various mammals

Veltman

McKone

Huijbregts

et al. 2009

Toxicology and Applied Pharmacology

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In the present study we develop and test a uniform model intended for single compartment analysis in the context of human and environmental risk assessment of airborne contaminants. The new aspects of the model are the integration of biological allometry with fugacity-based mass-balance theory to describe exchange of contaminants with air. The developed model is applicable to various mammalian species and a range of chemicals, while requiring few and typically well-known input parameters, such as the adult mass and composition of the species, and the octanol-water and air-water partition coefficient of the chemical.Accumulation of organic chemicals is typically considered to be a function of the chemical affinity for lipid components in tissues. Here, we use a generic description of chemical affinity for neutral and polar lipids and proteins to estimate blood-air partition coefficients (K ba ) and tissue-air partition coefficients (K ta ) for various mammals. This provides a more accurate prediction of blood-air partition coefficients, as proteins make up a large fraction of total blood components.The results show that 75% of the modeled inhalation and exhalation rate constants are within a factor of 2 from independent empirical values for humans, rats and mice, and 87% of the predicted blood-air partition coefficients are within a factor of 5 from empirical data. At steady-state, the bioaccumulation potential of air pollutants is shown to be mainly a function of the tissue-air partition coefficient and the biotransformation capacity of the species and depends weakly on the ventilation rate and the cardiac output of mammals.

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“…Factors such as genetics, gender, ethnicity, nutritional status, and behavior or lifestyle all contribute to the differences seen in responses to chemicals among individuals [13]. Thus, the standard of practice is to employ toxicity tests in laboratory animals to identify target sites of toxicity and dose-response information for hazard assessment applicable to a range of subpopulations of concern, including children.…”

Section: Routine Toxicity Tests: What Do They Teach Us?mentioning

confidence: 99%

Does The Standard Toxicological Testing Paradigm for Industrial Chemicals Apply to Screening for Children's Health Risks?

Plunkett¹,

Becker²

2008

TOTOXIJ

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Abstract:Questions have been raised concerning whether standard toxicological testing paradigms for characterizing hazards are applicable for children. In this paper, the standard toxicological testing paradigm for industrial chemicals 1 is examined. The analysis includes examination of the basic principles and elements of hazard characterization methodology based on animal toxicity data, examination of the characteristics of the standard toxicity tests that apply to assessing hazards of industrial chemicals to children's health, and an appraisal of specific industrial chemical hazard characterizations developed by USEPA covering more than 200 substances (High Production Volume (HPV) Challenge datasets 2 ) with regard to their relevancy for use in screening for potential risks to children's health. We conclude that the standard toxicity tests used for industrial chemicals that comprise the USEPA's HPV Challenge provide adequate information for developing screening-level hazard characterizations for children's health, and when coupled with child-specific exposure information should provide adequate screening-level risk evaluations for children.

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Human variability and susceptibility to trichloroethylene.

Cited by 30 publications

References 152 publications

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Bioaccumulation potential of air contaminants: Combining biological allometry, chemical equilibrium and mass-balances to predict accumulation of air pollutants in various mammals

Does The Standard Toxicological Testing Paradigm for Industrial Chemicals Apply to Screening for Children's Health Risks?

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