Pesticide use and inflammatory bowel disease in licensed pesticide applicators and spouses in the Agricultural Health Study.

BACKGROUND: Pesticide exposure has been linked to some autoimmune diseases and colorectal cancer, possibly via alteration of gut microbiota or other mechanisms. While pesticides have been linked to gut dysbiosis and inflammation in animal models, few epidemiologic studies have examined pesticides in relation to inflammatory bowel disease (IBD). OBJECTIVES: We evaluated use of pesticides and incident IBD in 68,480 eligible pesticide applicators and spouses enrolled in the Agricultural Health Study. METHODS: Self-reported IBD cases were identified from follow-up questionnaires between enrollment (1993-1997) and 2022. We evaluated IBD incidence in relation to self-reported ever use of 50 pesticides among applicators and spouses. We also explored associations with intensity-weighted lifetime days (IWLD) of pesticide use among male applicators. Covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression. RESULTS: We identified 454 IBD cases, including 227 among male applicators. In analyses with applicators and spouses combined, associations were positive (HR > 1.2) for ever vs. never use of five organochlorine insecticides, three organophosphate insecticides, one fungicide, and five herbicides. HRs were highest for dieldrin (HR = 1.59, 95%CI: 1.03, 2.44), toxaphene (HR = 1.61, 95%CI: 1.17, 2.21), parathion (HR = 1.42, 95%CI: 1.03, 1.95), and terbufos (HR = 1.53, 95%CI: 1.19, 1.96). We had limited power in many IWLD of pesticide use analyses and did not find clear evidence of exposure-response trends; however, we observed elevated HRs in all tertiles of IWLD use of terbufos compared to never use (T1 vs. never use HR = 1.52, 95%CI: 1.03, 2.24; T2 vs. never use HR = 1.53, 95%CI: 1.04, 2.26; T3 vs. never use HR = 1.51, 95%CI: 1.03, 2.23). CONCLUSIONS: Exposure to specific pesticides was associated with elevated hazards of IBD. These findings may have public health importance given the widespread use of pesticides and the limited number of known modifiable environmental risk factors for IBD.

Urinary metabolite concentrations of phthalate and plasticizers in infancy and childhood in the UNC baby connectome project.

INTRODUCTION: Existing evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood. METHODS: Urine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples). RESULTS: Most phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58-60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10-0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed. CONCLUSION: Metabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy.

Health Care Team Interventions to Reduce Distress Behaviors in Older Adults: A Systematic Review.

OBJECTIVES: This review examines health care team-focused interventions on managing persistent or recurrent distress behaviors among older adults in long-term residential or inpatient health care settings. METHODS: We searched interventions addressing health care worker (HCW) knowledge and skills related to distress behavior management using Ovid MEDLINE, Elsevier Embase, and Ovid PsycINFO from December 2002 through December 2022. RESULTS: We screened 6,582 articles; 29 randomized trials met inclusion criteria. Three studies on patient-facing HCW interactions (e.g. medication management, diagnosing distress) showed mixed results on agitation; one study found no effect on quality of life. Six HCW-focused studies suggested short-term reduction in distress behaviors. Quality-of-life improvement or decreased antipsychotic use was not evidenced. Among 17 interventions combining HCW-focused and patient-facing activities, 0 showed significant distress reduction, 8 showed significant antipsychotic reduction (OR = 0.79, 95%CI [0.69, 0.91]) and 9 showed quality of life improvements (SMD = 0.71, 95%CI [0.39, 1.04]). One study evaluating HCW, patient-, and environmental-focused intervention activities showed short-term improvement in agitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Novel health care models combining HCW training and patient management improve patient quality of life, reduce antipsychotic use, and may reduce distress behaviors. Evaluation of intervention's effects on staff burnout and utilization is needed.

Nontraditional Occupational Exposures to Crude Oil Combustion Disasters and Respiratory Disease Risk: A Narrative Review of Literature.

PURPOSE OF REVIEW: Burning of petroleum products has been consistently associated with adverse respiratory health effects. Combustion of crude oil, specifically, produces toxic byproducts, but there have been relatively few studies of health effects. Burning of crude oil is increasingly employed as a means of mitigating environmental disasters despite the potential health risks to workers involved in clean-up efforts. Here, we review epidemiological studies of respiratory effects following unique crude oil burning events to (1) characterize respiratory health effects from this nontraditional occupational exposure and (2) identify approaches used to characterize exposures that could be applied to future disaster-related studies. RECENT FINDINGS: We searched PubMed and EMBASE for references from inception to January 30, 2023. We also manually screened references cited in eligible articles. We identified 14 eligible publications. Our review suggests that exposure to crude oil combustion has adverse respiratory effects, including reduced lung function and increased occurrence of respiratory symptoms and disease. However, the evidence is inconsistent, and quality of data varied across studies. While some studies used quantitative, modeled exposure estimates, most used self-reported proxies of exposure. Although disasters involving crude oil combustion are relatively rare, limited evidence suggests that some worker populations may be at risk for respiratory effects from burning exposures in disaster settings. Future studies that use improved exposure assessment methods (e.g., personal monitors, remote sensing data) may help further quantify the respiratory risk from crude oil burning exposures.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. OBJECTIVES: To investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. RESULTS: We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 µg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 µg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). CONCLUSIONS: Among oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

Exposure to volatile hydrocarbons and neurologic function among oil spill workers up to 6 years after the Deepwater Horizon disaster.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, oil spill response and cleanup (OSRC) workers were exposed to toxic volatile components of crude oil. Few studies have examined exposure to individual volatile hydrocarbon chemicals below occupational exposure limits in relation to neurologic function among OSRC workers. OBJECTIVES: To investigate the association of several spill-related chemicals (benzene, toluene, ethylbenzene, xylene, n-hexane, i.e., BTEX-H) and total petroleum hydrocarbons (THC) with neurologic function among DWH spill workers enrolled in the Gulf Long-term Follow-up Study. METHODS: Cumulative exposure to THC and BTEX-H across the oil spill cleanup period were estimated using a job-exposure matrix that linked air measurement data to detailed self-reported DWH OSRC work histories. We ascertained quantitative neurologic function data via a comprehensive test battery at a clinical examination that occurred 4-6 years after the DWH disaster. We used multivariable linear regression and modified Poisson regression to evaluate relationships of exposures (quartiles (Q)) with 4 neurologic function measures. We examined modification of the associations by age at enrollment (<50 vs. ≥50 years). RESULTS: We did not find evidence of adverse neurologic effects from crude oil exposures among the overall study population. However, among workers ≥50 years of age, several individual chemical exposures were associated with poorer vibrotactile acuity of the great toe, with statistically significant effects observed in Q3 or Q4 of exposures (range of log mean difference in Q4 across exposures: 0.13-0.26 µm). We also observed suggestive adverse associations among those ≥ age 50 years for tests of postural stability and single-leg stance, although most effect estimates did not reach thresholds of statistical significance (p < 0.05). CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest deficits in neurologic function among OSRC workers who were age 50 years or older at study enrollment.

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore.

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.

Prediagnostic serum concentrations of organochlorine pesticides and non-Hodgkin lymphoma: A nested case-control study in the Norwegian Janus Serum Bank Cohort.

BACKGROUND: Much of the marked increase in incidence of non-Hodgkin lymphoma (NHL) over the past few decades remains unexplained. Organochlorines, including organochlorine pesticides (OCPs), have been implicated as possible contributors to the increase, but the evidence is inconsistent. OBJECTIVES: To investigate the relation between pre-diagnostic levels of OCPs and risk of NHL in a case-control study nested within the population-based Janus Serum Bank Cohort in Norway. METHODS: Prediagnostic concentrations of 11 OCPs or OCP metabolites were measured in baseline blood samples collected between 1972 and 1978 from 190 cases and 190 controls matched on sex, county, age at blood draw, and date of blood draw. We conducted conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for each quartile of lipid-corrected OCP/metabolite relative to the lowest quartile. RESULTS: We observed non-significantly elevated ORs across quartiles of ß-hexachlorocyclohexane compared to the lowest quartile (OR range: 1.40-1.82) although with no apparent monotonic exposure-response relationship. We also found an inverse association between risk of NHL and o,p'-DDT (OR for Q4 vs. Q1 = 0.44, 95% CI: 0.19, 1.01; p-trend = 0.05). In analyses stratified by age at blood collection and duration of follow-up, several other analytes, primarily chlordane-related compounds, showed inverse associations among younger participants or those with longer follow-up time between blood draw and NHL diagnosis. CONCLUSIONS: We found only limited evidence of positive association between selected OCPs and development of NHL.

Distinguishing Linkage Position and Anomeric Configuration of Glucose-Glucose Disaccharides by Water Adduction to Lithiated Molecules.

A method was developed to distinguish both the linkage position and the anomericity of all reducing and two nonreducing glucopyransosyl-glucose disaccharides using only electrospray ionization-mass spectrometry/mass spectrometry (ESI-MS/MS). Carbohydrates are well-known to form complexes with metal cations during electrospray ionization. Addition of a lithium salt to a solution containing a disaccharide, M, results in [M + Li]+ after ESI. Collision-induced dissociation of these ions creates product ions at m/z 187 and m/z 169 from cleavage of the glycosidic bond and are present for all disaccharides studied. Both of these product ions were found to adduct water after their formation in a quadrupole ion trap. The kinetics of this water adduction can be measured by isolating either of the product ions and waiting a short time (<1 s) before mass analysis. Additionally, for both product ions, only a fraction of the ions were able to adduct water. This unreactive fraction was measured along with the reaction rate, and the combination of these two values was found to be unique for each disaccharide. Additionally, after CID, a 1000 ms delay can be added, and the ratios of the resulting products ions of m/z 169, 187, and 205 can be used to distinguish linkage position and anomericity with a single tandem mass spectrometry experiment.

Distinguishing Biologically Relevant Hexoses by Water Adduction to the Lithium-Cationized Molecule.

A method to distinguish the four most common biologically relevant underivatized hexoses, d-glucose, d-galactose, d-mannose, and d-fructose, using only mass spectrometry with no prior separation/derivatization step has been developed. Electrospray of a solution containing hexose and a lithium salt generates [Hexose+Li]+. The lithium-cationized hexoses adduct water in a quadrupole ion trap. The rate of this water adduction reaction can be used to distinguish the four hexoses. Additionally, for each hexose, multiple lithiation sites are possible, allowing for multiple structures of [Hexose+Li]+. Electrospray produces at least one structure that reacts with water and at least one that does not. The ratio of unreactive lithium-cationized hexose to total lithium-cationized hexose is unique for the four hexoses studied, providing a second method for distinguishing the isomers. Use of the water adduction reaction rate or the unreactive ratio provides two separate methods for confidently (p ≤ 0.02) distinguishing the most common biologically relevant hexoses using only femtomoles of hexose. Additionally, binary mixtures of glucose and fructose were studied. A calibration curve was created by measuring the reaction rate of various samples with different ratios of fructose and glucose. The calibration curve was used to accurately measure the percentage of fructose in three samples of high fructose corn syrup (<4% error).

Childhood and adolescent residential and farm pesticide exposures and inflammatory bowel disease incidence in a U.S. cohort of women.

BACKGROUND AND AIMS: There are few known risk factors for inflammatory bowel disease (IBD), an autoimmune disease characterized by chronic intestinal inflammation. Use of specific pesticides has been associated with higher incidence of IBD among pesticide applicators and their spouses, but no study has examined pesticide exposure in early life, a period where the human immune system undergoes rapid changes. We evaluated pesticide use during childhood and adolescence and incidence of IBD among US women enrolled in the Sister Study. METHODS: Incident IBD diagnoses between enrollment (2003-2009) and 2021 were identified and validated with medication use and colectomy/colostomy surgery. We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for the relationship of childhood/adolescent residential and farm pesticide exposures with IBD incidence using Cox models, accounting for age, race and ethnicity, education, smoking, and birth year. RESULTS: We identified 277 incident IBD cases among 48,382 eligible participants. IBD hazard was elevated among those whose childhood residence was regularly treated with pesticides, especially among those who ever personally applied pesticides (HR = 1.39, 95%CI: 0.65, 2.99). We observed a positive association between IBD and exposure to broadcast pesticide sprays before DDT was banned (>6 times vs. never HR = 1.56, 95%CI: 1.06, 2.31). Among participants who lived on a farm during childhood/adolescence for ≥1 year (N = 9162), IBD hazards were higher among those who were in crop fields during pesticide application (HR = 2.06, 95%CI: 0.94, 4.51) and who ever personally applied pesticides on crops (HR = 1.85, 95%CI: 0.81, 4.18) or livestock (HR = 2.58, 95%CI: 1.14, 5.83). CONCLUSION: Early-life pesticide exposure may be a novel risk factor for IBD. Practices that reduce pesticide exposure during early life may help reduce the burden of this disease.

Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study.

BACKGROUND: Nitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD). OBJECTIVES: We investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation. METHODS: We performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993-1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999-2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake. RESULTS: We identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C

Volatile Hydrocarbon Exposures and Incident Coronary Heart Disease Events: Up to Ten Years of Follow-up among Deepwater Horizon Oil Spill Workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. OBJECTIVES: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. METHODS: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. RESULTS: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR=1.14-1.44). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with ≤high school education, and workers with body mass index <30 kg/m2. No apparent positive association was observed for the BTEX-H mixture. CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859.

Fine Particulate Matter and Lung Function among Burning-Exposed Deepwater Horizon Oil Spill Workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, controlled burning was conducted to remove oil from the water. Workers near combustion sites were potentially exposed to increased fine particulate matter [with aerodynamic diameter ≤2.5µm (PM2.5)] levels. Exposure to PM2.5 has been linked to decreased lung function, but to our knowledge, no study has examined exposure encountered in an oil spill cleanup. OBJECTIVE: We investigated the association between estimated PM2.5 only from burning/flaring of oil/gas and lung function measured 1-3 y after the DWH disaster. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster and had lung function measured at a subsequent home visit (n=2,316). PM2.5 concentrations were estimated using a Gaussian plume dispersion model and linked to work histories via a job-exposure matrix. We evaluated forced expiratory volume in 1 s (FEV1; milliliters), forced vital capacity (FVC; milliliters), and their ratio (FEV1/FVC; %) in relation to average and cumulative daily maximum exposures using multivariable linear regressions. RESULTS: We observed significant exposure-response trends associating higher cumulative daily maximum PM2.5 exposure with lower FEV1 (p-trend=0.04) and FEV1/FVC (p-trend=0.01). In comparison with the referent group (workers not involved in or near the burning), those with higher cumulative exposures had lower FEV1 [-166.8mL, 95% confidence interval (CI): -337.3, 3.7] and FEV1/FVC (-1.7, 95% CI: -3.6, 0.2). We also saw nonsignificant reductions in FVC (high vs. referent: -120.9, 95% CI: -319.4, 77.6; p-trend=0.36). Similar associations were seen for average daily maximum PM2.5 exposure. Inverse associations were also observed in analyses stratified by smoking and time from exposure to spirometry and when we restricted to workers without prespill lung disease. CONCLUSIONS: Among oil spill workers, exposure to PM2.5 specifically from controlled burning of oil/gas was associated with significantly lower FEV1 and FEV1/FVC when compared with workers not involved in burning. https://doi.org/10.1289/EHP8930.

Identifying the D-Pentoses Using Water Adduction to Lithium Cationized Molecule.

A method has been developed that is capable of distinguishing an exhaustive list of underivatized D-pentoses with only a mass spectrometer. Electrospray ionization (ESI) of a solution containing a pentose and a lithium salt yields [Pentose + Li]+. These lithiated pentoses adduct water in a quadrupole ion trap. The reaction rate of water adduction is unique for several of the pentose isomers. Additionally, there are multiple potential gas-phase lithiation sites to form [Pentose + Li]+. A mixture of ions with at least one reactive (water adducting) and at least one unreactive (non-adducting) lithiation site is formed for each pentose. The water adduction reaction rate along with the unreactive fraction of lithiated pentose can be used to completely discriminate all D-pentoses. Graphical Abstract ᅟ.