Elucidating mechanisms of chlorine toxicity: reaction kinetics, thermodynamics, and physiological implications

Industrial and transport accidents, accidental releases during recreational swimming pool water treatment, household accidents due to mixing bleach with acidic cleaners, and, in recent years, usage of chlorine during war and in acts of terror, all contribute to the general and elevated state of alert with regard to chlorine gas. We here describe chemical and physical properties of Cl2 that are relevant to its chemical reactivity with biological molecules, including water-soluble small-molecular-weight antioxidants, amino acid residues in proteins, and amino-phospholipids such as phosphatidylethanolamine and phosphatidylserine that are present in the lining fluid layers covering the airways and alveolar spaces. We further conduct a Cl2 penetration analysis to assess how far Cl2 can penetrate the surface of the lung before it reacts with water or biological substrate molecules. Our results strongly suggest that Cl2 will predominantly react directly with biological molecules in the lung epithelial lining fluid, such as low-molecular-weight antioxidants, and that the hydrolysis of Cl2 to HOCl (and HCl) can be important only when these biological molecules have been depleted by direct chemical reaction with Cl2. The results from this theoretical analysis are then used for the assessment of the potential benefits of adjuvant antioxidant therapy in the mitigation of lung injury due to inhalation of Cl2 and are compared with recent experimental results.

Toxicity screening and evaluating in chlorination disinfection of wastewater reclamation processes

Reclamation and re-use of wastewater is one of the most effective ways to alleviate the shortage of water resources, while the safety of reclaimed water becomes one of the critical problems for protecting human health and the ecosystem. While a toxicity test can vividly reflect biological effects of chemicals as a whole, in this study, the Microtox test was used to screen toxicity changes of wastewater during conventional reclamation processes. The results showed that toxicities of water samples decreased continuously along reclamation processes except chlorination/dechlorination in which the toxicity increased significantly. Furthermore, as for different forms of residual chlorine, toxicity of wastewater was quite different with increasing chlorine dosage. NH3-N had a trend to decrease toxicity of disinfected wastewater, while UV254 had a trend to increase toxicity. It was found that there was a good linear relationship between toxicity formation and UV254/NH3-N ratio for wastewater after disinfection with combined chlorine form before peak-point.

Quantification of the Toxicity of Aqueous Chlorine to Spores of Penicillium digitatum and Geotrichum citri-aurantii

Chlorine toxicity to Penicillium digitatum and Geotrichum citri-aurantii, causes of green mold and sour rot of citrus, respectively, was quantified. In 3% wt/vol NaHCO3 containing 200 µg free chlorine per ml at pH 8.3, 95% of P. digitatum spores died (LT95) by 180 s at 5°C, while only 32 s were required at 24°C. The LT95 of G. citri-aurantii arthrospores was 108 and 31 s at 5 and 24°C, respectively. Mortality slowed 2- to 4-fold for each unit of increase from pH 7 to 10. The LT95 of P. digitatum spores in 200 µg free chlorine per ml at 24°C at pH 7, 8, 9, and 10 was 13.2, 19.1, 29.4, and 88.4 s, respectively. The LT95 of G. citri-aurantii at pH 7, 8, 9, and 10 was 3.0, 12.6, 56.6, and 114 s, respectively. Models were prepared describing mortality. Brief immersion in 200 µg free chlorine per ml reduced viable spores of P. digitatum and G. citri-aurantii from 106 to 103 spores per lemon, and naturally occurring yeast and molds from 106 to 104 CFU. In fruit wound-inoculated and immersed 24 h later in water, 4,000 µg free chlorine per ml, or 3% wt/vol NaHCO3, green mold occurrence after storage was 98.5, 68.3 and 7.5%, respectively.

Developmental Toxicity Study of Orally Administered Lithium Hypochlorite in Rats

The purpose of this study was to examine the developmental toxicity of lithium hypochlorite in Sprague-Dawley rats. Groups of 25 pregnant rats received lithium hypochlorite at dosages of 0 (vehicle-reverse osmosis deionized water), 10, 50, 100, or 500 mg/kg/day, via oral gavage once daily on days 6 through 15 of gestation. The test solution was not adjusted for ion concentration. All dosages were given at a volume of 10 m/kg per day, adjusted daily for body weight. The rats were given RO deionized water for drinking, to prevent ingestation of chlorine or any other ions except those provided by the test substance. Clinical signs, body weight, and feed consumption were recorded daily during the dosage and postdosage periods. Caesarean-sectioning of the rats occurred on day 20 of gestation. Evaluations were made for pregnancy, number and placement of implantations, early and late resorptions, fetal viability, and number of corpora lutea. Fetuses were subsequently examined for gender, body weight, and gross external, soft tissue, and skeletal alterations. Significant (p ≤ 0.05 to p ≤ 0.01) maternal toxicity was observed in the 500 mg/kg per day dosage group, which included maternal death, clinical signs, gross necropsy findings, and inhibited maternal body weight gain and feed consumption. These effects were consistent with those expected from chlorine toxicity. The only effects of this dosage on embryo-fetal development were small reversible delays in growth (decreased fetal body weight, wavy ribs and delayed ossification of the thoracic vertebrae (bifid centra), forepaw and hindpaw phalanges, and metatarsal and metacarpal bones). Average values for corpora lutea, implantation sites, litter sizes, live and dead fetuses, and resorptions were comparable in the five dosage groups andlor were within the range observed historically. On the basis of these data, both the maternal no-observable-adverse-effect level (NOAEL) and the developmental NOAEL for lithium hypochlorite were 100 mg/kg per day. These data are in agreement with other studies and demonstrate that developmental toxicity of lithium hypochlorite does not occur in the absence of overt maternal toxicity.