Search

The disposition of decabromodiphenyl ethane (DBDPE) was investigated based on concerns over its structural similarities to decaBDE, high potential for environmental persistence & bioaccumulation, and high production volume.In the present study, female Sprague Dawley rats were administered a single dose of [14C]-DBDPE by oral, topical, or IV routes. Another set of rats were administered 10 daily oral doses of 14C]-DBDPE. Male B6C3F1/Tac mice were administered a single oral dose.DBDPE was poorly absorbed following oral dosing, with 95% of administered [14C]-radioactivity recovered in the feces, 1% recovered in the urine and less than 3% in the tissues at 72 h. DBDPE excretion was similar in male mice and female rats. Accumulation of [14C]-DBDPE was observed in liver and the adrenal gland after 10 daily oral doses.The dermis was a depot for dermally applied DBDPE; conservative estimates predict ~14±8% of DBDPE may be absorbed into human skin in vivo; ~7±4% of the parent chemical is expected to reach systemic circulation following continuous exposure (24 h).Following intravenous administration, 6% of the dose was recovered in urine and 28% in the feces, while ~70% of the dose remained in tissues after 72h, with the highest concentrations found in the liver (42%) and lung (17%).

Levels of polybrominated diphenyl ether (PBDE) flame retardants have been increasing in humans and the environment for the past few decades. Human levels are markedly higher in the US than Europe. Although food appears to be a significant route of intake, food PBDE levels are not substantially higher in the US than Europe. House and office dust appear to be major routes of exposure with air believed to usually provide a lesser route of intake. Because there are very few measurements of airborne PBDE that have been performed in relevant microenvironments in the US, increased efforts to assess airborne PBDE in the US as sources of exposure are needed. This study reports, for the first time from a Southwestern US city in Texas, the results of measurements of airborne PBDE in multiple locations, two outdoor and six indoor (residential and office) from active air sampling with collection of a combination of both vapor- and particulate-phase PBDE. Higher PBDE levels were measured in indoor than outdoor air, whi...

Tributyltin and triphenyltin (TBT and TPT) are biocides that have been used to prevent fouling of boats, preserve wood, kill molluscs, and other uses. Due to observed effects on oysters and snails, their use in boat paints has been banned in many nations. However, use on ships and some uses other than as antifouling paints continue. These uses, the relative persistence of these compounds, their tendency to bioaccumulate, and their toxicity cause lingering concerns about risks to humans and non-human organisms. This paper outlines an integrated assessment of TBT and TPT. Based on prior human health and ecological assessments, it suggests that an integrated assessment that recognized common pathways of transport, fate and exposure, and common modes of action would be more efficient and complete than additional independent assessments. The presentation of risks in an integrated manner could also lead to better decisions by defining the various benefits of any management action.

Since the mid-1900s, the global environment has become increasingly contaminated with Persistent Organic Pollutants (POPs), including many with dioxin-like properties. These compounds generally have low water solubility, do not degrade readily in the environment, bioaccumulate in food chains, and have been linked to adverse health effects in both humans and wildlife. The presence of such compounds in terrestrial and aquatic food chains is relevant to those concerned with both human health and environmental protection because of the many common exposure pathways and biological effects among different species. In the past, some chemicals with health risks for humans have been identified following reports of adverse effects in wildlife. Integrating human and ecological risk assessments may improve society's ability to manage the design, manufacture, use and disposal of chemicals in a safe and efficient manner. This can be demonstrated with this case study, which summarizes approaches to evaluating the source...

(1999). TEFs: A Practical Approach to a Real-World Problem. Human and Ecological Risk Assessment: An International Journal: Vol. 5, No. 1, pp. 13-24.

Induction of CYP1A1 is one of the best characterized responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). EROD activity has been used as an enzymatic marker for CYP1A1 following TCDD treatment. Enzymatic markers for the induction of CYP1A2 by TCDD are not as well characterized. The present study examines the relationship between CYP1A1 and CYP1A2 protein and the corresponding enzymatic markers. Induction of hepatic ethoxyresorufin O-deethylase (EROD) activity and methoxyresorufin O-demethylase (MEROD) and acetanilide 4-hydroxylase (ACOH) activity (both markers for CYP1A2) were analyzed in 8-wk-old male and female Fischer 344 rats treated orally with either 0, 0.1, 0.3, 1.0, or 3.0 micrograms TCDD/kg. There were no sex differences in basal EROD or ACOH activity. MEROD activity was significantly greater in control males than in control females. Significant induction of EROD activity in females occurred at slightly lower doses of TCDD compared to males (0.1 vs. 0.3 micrograms/kg, respectively); however, a greater absolute and a larger fold induction of EROD activity was seen in males compared to females at all doses tested except 0.1 micrograms/kg. EROD activity did not attain a maximum in either sex. Similarly, MEROD activity was induced at lower doses of TCDD in females than in males (0.1 vs. 0.3 micrograms/kg, respectively). MEROD activity was maximally induced at 0.3 micrograms/kg in males. In females, MEROD did not attain maximum induction at the doses tested. ACOH activity was induced at doses as low as 0.3 micrograms/kg in both sexes, and the dose-dependent increases in activity were equivalent in males and females. Both ACOH and MEROD activity correlated well with CYP1A2 levels as determined by Western blot analysis, although there was a greater fold induction of protein than either MEROD or ACOH. Although MEROD and ACOH are both markers for the same response, MEROD activity may be a more useful marker because it is the quicker and more sensitive of the two assays.

A recent biomonitoring study “Bisphenol A, Bisphenol S, and 4-Hydroxyphenyl 4-Isoprooxyphenylsulfone (BPSIP) in Urine and Blood of Cashiers” reported on levels of BPA, BPS, and a novel BPS-derivative (BPSIP) in cashiers compared to non-cashiers. Our study was the first to detect BPSIP in humans. In this commentary we discuss our findings in the context of considering bisphenols as a class in health assessments and how technological advances in exposure assessment could be utilized to more efficiently identify emerging chemicals of interest.

Polybrominated dibenzo-p-dioxins and dibenzofurans have been identified as potential environmental contaminants. The present studies were designed to characterize the chemical disposition of a tetrabrominated dibenzofuran. The isomer-specific pattern of 1,2,7,8-tetrabromodibenzofuran (TBDF) was chemically characterized using high-pressure liquid chromatography, gas chromatography/mass spectrometry, infrared absorption, and proton nuclear magnetic resonance techniques. The absorption, distribution, and elimination of 1,2,7,8-[4,6-3H]-TBDF were examined in the rat following a single oral, dermal, or intravenous dose of 1 nmol/kg. The 1,2,7,8-TBDF was rapidly excreted in the bile (approximately 50% of the dose in 8 h). Likewise, over half of the administered dose was found in the feces and intestine contents 24 h after iv administration and in feces 72 h after oral administration. Thus, the half-life of 1,2,7,8-TBDF is approximately 1 d. Major tissue depots included the liver, adipose tissue, and skin. The decline in hepatic concentrations observed in the iv and bile studies occurred in conjunction with metabolic elimination as well as a slight accumulation in adipose tissue. Dermal absorption of 1,2,7,8-TBDF, quantified as the amount contained in tissues (excluding the skin site) and excreta at 72 h, was estimated to be 29% of the administered dose. Thus, the general disposition profile of 1,2,7,8-TBDF in the rat is similar to that of other polyhalogenated aromatic hydrocarbons. Due to its rapid elimination, which is consistent with its predicted susceptibility to metabolic elimination, acute exposure to 1,2,7,8-TBDF would not be expected to result in the degree of toxicity associated with other more persistent congeners.

Phthalates are a group of chemicals used to make plastics softer and more flexible. They are used in hundreds of products, such as vinyl flooring, adhesives, detergents, lubricating oils, automotive plastics, plastic clothes (raincoats) and personal-care products (soaps, shampoos, hair sprays and nail polishes). People are exposed to phthalates by eating and drinking foods that have been in contact with containers and products containing phthalates. To a lesser extent, exposure can occur from breathing in air that contains vapors or dust contaminated with phthalate particles. Once phthalates enter a person's body, they are converted into breakdown products that pass out quickly in urine. However, biomonitoring studies that measure urine metabolites in humans show widespread exposure to phthalates. Phthalates have been labeled as potential endocrine disrupting chemicals (EDCs) because studies have demonstrated that they interfere with hormones of the reproductive system. Recently, we reported for the first...

Humans have been exposed to azodicarbonamide (ADA) by inhalation where bulk quantities of ADA are handled in the workplace. Responses of some workers have led to concern for the potential irritant and sensitizing properties of inhaled ADA. This study examined the effects of inhaling ADA on lung structure and function of guinea pigs during and after an acute exposure. Groups of 20 guinea pigs were exposed to each of 3 concentrations of ADA (19, 58, and 97 mg/m3), plus air as a control, for 1 hr. Pulmonary function was measured before exposure (baseline), during exposure, immediately after exposure and 24 hr after exposure. Dynamic compliance (Cdyn), total pulmonary resistance (RL), tidal volume (VT), respiratory frequency and minute volume were measured. In addition, gross necropsies and histological examinations of respiratory tract tissues were done either immediately following the exposure or 24 hr after exposure. There were no effects of ADA exposure on gross necropsy, histology, Cdyn, or RL. Some significant, concentration-related decreases in VT, respiratory frequency and minute volume were seen. The magnitudes of these changes were small: the largest change was seen in minute volume, amounting to a 24% decrease in the high concentration group. Inhalation exposure of guinea pigs to ADA at concentrations of up to 97 mg/m3 resulted in minor changes in pulmonary function without any changes in lung histology.

Polybrominated biphenyl (PBB) mixtures are contaminated with brominated naphthalenes formed during the synthesis procedure. Synthesis of hexabromonaphthalenes (HBNs) by direct bromination of naphthalene results in a mixture of two isomers. The identity of the major isomer, 1,2,3,4,6,7‐HBN, was previously confirmed (Birnbaum et al., 1983). The minor isomer is definitively identified as 2,3,4,5,6,7‐HBN by high‐field nuclear magnetic resonance (NMR) spectroscopic analysis of brominated [1‐ 13 C]naphthalene‐derived products. This isomer is extremely persistent and can be isolated from the liver of rats 10 d after treatment with the HBN mixture by a combination of solvent extraction and partition and adsorption chromatography.

1,3-Butadiene is produced commercially for use in the manufacture of elastomers, polymers and other chemicals. Recent inhalation carcinogenicity studies of butadiene indicate that B6C3F1 mice are more sensitive to the tumorigenic effects of inhaled butadiene than are Sprague Dawley rats. The purpose of this investigation was to determine if there were differences in distribution in tissues of inhaled butadiene between rats and mice. Male Sprague Dawley rats and B6C3F1 mice were exposed nose-only for 3.4 hr to (mean +/- SE) 1220 +/- 71 micrograms 14C-butadiene/L air and 121 +/- 2 micrograms 14C-butadiene/L air, respectively. Radioactivity was distributed widely in tissues immediately following exposure of both rats and mice to 14C-butadiene. In both species, respiratory tract tissue (lung, trachea, nasal turbinates), gastrointestinal tract (small and large intestine), liver, kidneys, urinary bladder and pancreas contained high concentrations of radioactivity within 1 hr after the end of exposure. In all cases, tissues of mice contained 15 to 100 times the concentration of 14C-butadiene equivalents per mumole of butadiene inhaled than did rats. For both rats and mice, elimination of 14C from tissues and blood was rapid, with 77% to 99% of the initial tissue burden being eliminated with half-times of 2 to 10 hr. Within 1 hr after the end of exposure, all rat tissues retained a substantial amount of 14C that was associated with volatile material (20% to 40% of the total 14C in tissues) that was probably butadiene and/or metabolites. A similar observation was noted in mouse liver, the only tissue of mice examined.(ABSTRACT TRUNCATED AT 250 WORDS)

The disposition and metabolism of o-benzyl-p-chlorophenol (BCP) were studied in male Fischer-344 rats. Three days after oral administration of [14C]BCP at 10, 100, or 1000 mg/kg, more than 90% of each dose was excreted in urine and feces. Comparison of disposition after intravenous, dermal, or oral administration indicated that BCP was not completely absorbed from the gastrointestinal tract or skin. Biliary excretion of BCP was dose-dependent, with proportionally less BCP-derived radioactivity being excreted in the bile as the dose was raised. The results also indicated that enterohepatic circulation was involved in BCP disposition. The major in vivo metabolites were glucuronyl conjugates of BCP and hydroxy-BCP. Glutathione conjugates were also present in urine. In vitro metabolism studies support the observation that microsomal oxidation and glutathione and glucuronyl conjugation play major roles in BCP metabolism. Spleen, kidney, and liver contained the highest tissue concentrations of BCP-derived radioactivity. The presence of more nonextractable BCP-derived radioactivity in kidney than in liver is compatible with the hypothesis that covalent binding of BCP to renal tissue may be associated with BCP-induced nephrotoxicity.