Chlorine toxicokinetics

In a study with captive male American kestrels (Drouillard et al. 2001), birds were dosed with Aroclor-contaminated diet and the toxicokinetics of 42 PCB congeners contained therein was stndied. Those congeners that were most rapidly cleared contained vicinal meta-para hydrogen substituents on at least one phenyl ring. This provides further evidence for the importance of open (i.e., not substituted by chlorine) meta-para positions for metabolic attack, an issue that will be returned to in the next section (Section 6.2.3). 

Kennedy, C.J. 1990. Toxicokinetic Studies of Chlorinated Phenols and Polycyclic Aromatic Hydrocarbons in Rainbow Trout (Oncorhynchus mykiss). Ph.D. Diss., Simon Fraser Univ., B.C., Canada. 188 pp. 

These experts collectively have knowledge of chlorine dioxide and chlorite s physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of chlorine dioxide and chlorite. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

No information was located regarding age-related differences in toxicokinetic parameters for chlorine dioxide or chlorite. 

Comparative Toxicokinetics. No studies were located in which toxicokinetics of chlorine dioxide or chlorite were examined in humans. Chlorine dioxide is used as a drinking water disinfectant and readily forms chlorite (CIO2 ) in aqueous environments. Therefore, humans would be most likely to encounter chlorine dioxide or chlorite via the oral exposure route. Currently, available toxicokinetic information is restricted to animal studies. Additional studies could be designed to examine toxicokinetics in humans orally exposed to chlorine dioxide or chlorite. Results of human and animal studies could then provide a basis for development of PBPK models for species extrapolation. 

Children s Susceptibility. Neurodevelopmental delays and postnatal changes in serum thyroid hormone levels have been observed in animals following exposure of their mothers to chlorine dioxide or chlorite during gestation and/or lactation (Carlton and Smith 1985 Carlton et al. 1987 Gill et al. 2000 Mobley et al. 1990 Orme et al. 1985 Taylor and Pfohl 1985 Toth et al. 1990). It is not known whether age-related differences in toxicokinetic parameters exist for chlorine dioxide or chlorite. Additional studies should be designed to further examine neurodevelopmental toxicity and underlying mechanisms. 

The assumption that PBBs and PBDEs share many toxicological characteristics with PCBs also does not consider geometrical differences due to the higher atomic weight and considerably larger molecular volume of bromine compare to chlorine (Hardy 2000, 2002). These differences contribute to dissimilar physical/chemical properties that can influence the relative toxicokinetics and toxicities of the chemicals. 

This chapter reviews the physical and chemical properties and toxicokinetic, toxicologic, and epidemiologic data on chlorine. The Subcommittee on Submarine Escape Action Levels used this information to assess the health risk to Navy personnel aboard a disabled submarine from exposure to chlorine gas and to evaluate the submarine escape action levels (SEALs) proposed to avert serious health effects and substantial degradation in crew performance from short-term exposure (up to 10 d). The subcommittee also identifies data gaps and recommends research relevant for determining the health risk attributable to exposure to chlorine. 

There are few toxicokinetic studies of chlorine inhalation, and there have been no toxicokinetic studies on dermal exposure to chlorine. 

Chlorine is considered a direct-acting irritant to the target tissues, the eyes and respiratory tract. Death is due to acute respiratory failure. Chlorine gas reacts at the site of contact and very little of the chemical is absorbed into the bloodstream (Eaton and Klaassen, 2001). Any chlorine that is absorbed becomes part of the body pool of chlorine, and toxicokinetics is not involved in the mechanism of action. 

Chlorine is a direct-acting irritant to the eyes and respiratory tract. The mechanisms of action for both irritation and lethal effects are described. Toxicokinetics is not involved in the mechanism of action. The relationship between concentration and exposure duration for the set endpoints of irritancy and mortality can be described mathematically. There are no recommendations for further research. 

Acute toxicity and toxicokinetics of PCDEs have been reported to be dependent on the number and position of chlorine [83]. Lower chlorinated PCDEs, PCDE 3 (4-monoCDE), PCDE 7 (2,4-diCDE), PCDE 28 (2,4,4 -triCDE), and PCDE 74 (2,4,4, 5-tetraCDE), were studied in brook trout (Salvelinus fontinalis). The LC50 (24 h) of PCDEs 3 and 7 were 1.4 mg 1 1 and 1.24 mg 1, respectively, but the toxicities of PCDEs 28 and 74 were less. 

---