Evaluation of potential toxicity of smoke from controlled burns of furnished rooms - effect of flame retardancy.

It has been reported that incorporation of fire retardants into home furnishings and electronics increases the toxicity of smoke produced during combustion in house fires. Studies have been limited to exercises in analytical chemistry but the biological effects of emissions, particularly regarding chronic toxicity, have not been investigated. The combustion of furnishings with and without chemical flame retardants (FR) regarding (1) ignition resistance and fire progression, (2) chemical composition of smoke (analytical chemistry), and (3) toxicity was compared. Data demonstrated that flame retarded furnishings slowed the generation of toxic levels of acutely toxic gases. The potential chronic toxicity of smoke was assessed using the ToxTracker® assay. Smoke samples from rooms with less flame retarded furnishings exhibited a lesser response in this assay than smoke samples from rooms with flame retarded furnishings. Chemicals associated with activation of the aryl hydrocarbon receptor (AHR), namely benzo[b]fluoranthene, benzo[a]anthracene, benzo[a]pyrene, chrysene, and indeno[1,2,3-cd]pyrene, were not found in smoke from more flame retarded furnished rooms, but were present only in smoke from rooms with less flame retarded furnishings. In conclusion, smoke resulting from combustion of flame retarded furnishings did not increase indicators of potential chronic toxicity hazards relative to non-flame retarded furnishings.

Subchronic toxicology of tetrabromobisphenol A in rats.

Tetrabromobisphenol A (TBBPA) is used to protect a wide range of electrical and electronic equipment, consumer electronics and office and communication equipment from catching fire. TBBPA reacts covalently with other monomers becoming an integral part of the cross-linked molecular structure. This study was conducted to evaluate the subchronic toxicity of TBBPA administered by gavage daily for 13 weeks at 0, 100, 300, and 1000 mg/kg/day in male and female CD® rats. A 6-week post-treatment control and 1000 mg/kg/day recovery groups were included. TBBPA exerted no marked effect on the rate of mortality, clinical signs, body or organ weights, feed consumption, histopathology, urinalysis, ophthalmology, and neurological outcomes in a functional observation battery, motor activity, serum thyroid stimulating hormone, serum triiodothyronine, or other serum chemistries. Although differences were observed for bilirubin and alkaline phosphatase, the observed alterations were within the normal range and thus were neither biologically or toxicologically meaningful. The single thyroid-related parameter affected by TBBPA was a reduction in serum thyroxine levels, but the decrease was not of sufficient magnitude to induce other more sensitive indicators of thyroid perturbation. The No Observed Adverse Effect Level was at least 1000 mg/kg/day, the highest dose tested. Based on an upper bound aggregate exposure for adults estimated by the European Union, the margin of exposure is approximately 5000, suggesting that, for the endpoints examined in this study, exposure to TBBPA presents a reasonable certainty of no harm.

Evaluation of the utility of the lifetime mouse bioassay in the identification of cancer hazards for humans.

Limited testing resources, the need to limit animal use, and the demand for better knowledge about carcinogenic hazards require that the carcinogenicity testing paradigm based on lifetime cancer bioassays in rats and mice should be as efficient and reliable as possible. We have therefore reevaluated the rodent bioassay, particularly for nongenotoxic chemicals and conducted a rigorous examination of the 710 substances listed in the Carcinogenic Potency Database (CPDB) that were tested in both mice and rats. The CPDB is a web-based database that provides access to the literature and the results of 6540 bioassays on 1547 chemicals that have been published in the general literature through 2001 and by the National Cancer Institute/National Toxicology Program through 2004. Only three chemicals (o-benzyl-p-chlorophenol, Elmiron®, p-tolylurea) were identified as unequivocally non-genotoxic, mouse non-liver carcinogens. A careful analysis showed that their carcinogenicity in mice is irrelevant for assessment of human cancer hazards. This is consistent with data showing, with a few well-known exceptions, that non-genotoxic carcinogens in rodents are considered to be non-carcinogenic to humans. As a result, we propose that the inclusion of the mouse bioassay in the standard assessment scheme for non-genotoxic chemicals is no longer necessary.

Toxicologic significance of histologic change in the larynx of the rat following inhalation exposure: a critical review.

The larynx is a site in the respiratory tract of animals that often shows a response to inhaled substances. In many cases, the most sensitive endpoint in repeated dose inhalation studies is squamous metaplasia (often of minimal severity) of the larynx. The U.S. Environmental Protection Agency has speculated that squamous metaplasia in the rodent larynx might be a pre-neoplastic lesion or a precursor to other serious effects and has proposed to use the effect of squamous metaplasia occurring in subchronic inhalation toxicology studies as a toxicologic endpoint for use in quantitative risk assessment [U.S. Environmental Protection Agency, 2006a. Reregistration Eligibility Decision for MGK-264, U.S. Environmental Protection Agency, 2006b, Reregistration Eligibility Decision for Piperonyl Butoxide, U.S. Environmental Protection Agency, 2006c. Reregistration Eligibility Decision for Pyrethrins]. To reach a conclusion as to its significance, we sought to establish the nature of this effect in the relevant context of rodent inhalation studies. A comprehensive review of the literature shows that laryngeal metaplasia can be produced by a wide range of chemically dissimilar substances, and even by "non-chemical" means such as irritation by aerosols and particles, and dehydration by alcohols or low humidity air. There is no published evidence that this effect is pre-neoplastic and it is clearly and repeatedly characterized as an adaptive response. Moreover, the well-differentiated character of laryngeal squamous metaplasia, the reversibility of incidence and severity of it during recovery periods, combined with no significant clinical observations and the lack of progression over time indicates that this response is adaptive and should not be considered to be indicative of significant human risk. We therefore conclude that squamous metaplasia of the rodent larynx is not a relevant toxicologic endpoint.