Incorporating concepts of inequality and inequity into health benefits analysis

BACKGROUND: Although environmental policy decisions are often based in part on both risk assessment information and environmental justice concerns, formalized approaches for addressing inequality or inequity when estimating the health benefits of pollution control have been lacking. Inequality indicators that fulfill basic axioms and agree with relevant definitions and concepts in health benefits analysis and environmental justice analysis can allow for quantitative examination of efficiency-equality tradeoffs in pollution control policies. METHODS: To develop appropriate inequality indicators for health benefits analysis, we provide relevant definitions from the fields of risk assessment and environmental justice and consider the implications. We evaluate axioms proposed in past studies of inequality indicators and develop additional axioms relevant to this context. We survey the literature on previous applications of inequality indicators and evaluate five candidate indicators in reference to our proposed axioms. We present an illustrative pollution control example to determine whether our selected indicators provide interpretable information. RESULTS AND CONCLUSIONS: We conclude that an inequality indicator for health benefits analysis should not decrease when risk is transferred from a low-risk to high-risk person, and that it should decrease when risk is transferred from a high-risk to low-risk person (Pigou-Dalton transfer principle), and that it should be able to have total inequality divided into its constituent parts (subgroup decomposability). We additionally propose that an ideal indicator should avoid value judgments about the relative importance of transfers at different percentiles of the risk distribution, incorporate health risk with evidence about differential susceptibility, include baseline distributions of risk, use appropriate geographic resolution and scope, and consider multiple competing policy alternatives. Given these criteria, we select the Atkinson index as the single indicator most appropriate for health benefits analysis, with other indicators useful for sensitivity analysis. Our illustrative pollution control example demonstrates how these indices can help a policy maker determine control strategies that are dominated from an efficiency and equality standpoint, those that are dominated for some but not all societal viewpoints on inequality averseness, and those that are on the optimal efficiency-equality frontier, allowing for more informed pollution control policies

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5 × 10−5, 5 × 10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9–10 weeks age) via nose-only inhalation (INH) exposure for 1 h. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal injection (IP) and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated time points and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 h post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the TK and genotoxicity of NNK.</jats:p

14-Day Nose-Only Inhalation Toxicity and Haber’s Rule Study of NNK in Sprague-Dawley Rats

Abstract 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. However, repeated inhalation toxicity data on NNK, which is more directly relevant to cigarette smoking, are currently limited. In the present study, the subacute inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9–10 weeks age; 16 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.8, 3.2, 12.5, or 50 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.03, 0.11, 0.41, or 1.65 mg/L air) for 1 h/day for 14 consecutive days. Toxicity was evaluated by assessing body and organ weights; food consumption; clinical pathology; histopathology observations; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); O6-methylguanine DNA adduct formation; and blood and bone marrow micronucleus frequency. Whether the subacute inhalation toxicity of NNK followed Haber’s Rule was also determined using additional animals exposed 4 h/day. The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic histopathological lesions in the nose. The lowest-observed-adverse-effect level (LOAEL) was 0.8 mg/kg BW/day or 0.03 mg/L air for 1 h/day for both sexes. An assessment of Haber’s Rule indicated that 14-day inhalation exposure to the same dose at a lower concentration of NNK aerosol for a longer time (4 h daily) resulted in greater adverse effects than exposure to a higher concentration of NNK aerosol for a shorter time (1 h daily).</jats:p