Publications

INTRODUCTION

The U.S. Environmental Protection Agency's (EPA's) Toxicity Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk assessment. We conducted a case study to compare ToxCast data with endpoints from other in vitro and in vivo studies for two data-rich pesticides: endosulfan and methidathion.

METHODS

ToxCast assays for endocrine disruption, development (zebrafish), and neurotoxicity were qualitatively compared to traditional neurotoxicity, developmental and reproductive toxicity findings. We also used in vitro-in vivo extrapolation to convert half-maximal activity concentrations in active ToxCast assays to rat oral equivalent doses, and quantitatively compared these to the lowest observable effect level (LOEL) from in vivo studies.

RESULTS

Endosulfan was inactive for GABAA R, unlike in vivo; but active with dopamine transporter assays and was neurotoxic in zebrafish as expected. Methidathion was not active for these endpoints in vivo or in vitro. Acetylcholinesterase inhibition was ToxCast-inactive, although both pesticides are inhibitors in vivo. ToxCast results were generally inactive for endosulfan estrogen receptor agonism and androgen receptor antagonism unlike in vivo. Calculated oral equivalent doses for estrogen receptor and androgen receptor pathways and for zebrafish assays for both compounds were generally consistent with in vivo LOELs. Endosulfan showed neurotoxicity and both pesticides showed developmental effects in the zebrafish assays, although methidathion is not developmentally toxic in vivo.

CONCLUSIONS

ToxCast's predictions showed concordance on some endpoints and nonconcordance, consisting mainly of false inactives, in several critical endpoints, likely due to a lack of metabolic activation and limitations in assay design. Zebrafish assays were good predictors of developmental toxicity and neurotoxicity for endosulfan.

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical neuroradiological condition characterized by insidious onset of neurological symptoms associated with radiological findings indicating posterior leukoencephalopathy. PRES secondary to cerebrospinal fluid (CSF) leak leading to intracranial hypotension is not well recognized etiology of this condition. Herein, we report a case of PRES that occurred in the setting of CSF leak due to inadvertent dural puncture. Patient underwent suturing of the dural defect. Subsequently, his symptoms resolved and a repeated brain MRI showed resolution of brain lesions. The pathophysiology and mechanistic model for developing PRES in the setting of intracranial hypotension were discussed. We further highlighted the importance of tight blood pressure control in patients with CSF leak and suspected intracranial hypotension because they are more vulnerable to develop PRES with normal or slightly elevated bleed pressure values.

BACKGROUND

One of the most common causes of death among homeless and unstably housed women is acute intoxication where cocaine is present. While correlates of stimulant use have been determined in prior research, few studies have assessed risk factors of use specifically in this high-risk population.

METHODS

We sampled biological women with a history of housing instability from community-based venues to participate in a cohort study. Baseline and 6-month follow-up data were used to determine the relative risk of stimulant use (crack cocaine, powder cocaine or methamphetamine) among individuals who did not use at baseline.

RESULTS

Among 260 study participants, the median age was 47 years, 70% were women of color; 47% reported having unmet subsistence needs and 53% reported abstinence from stimulants at baseline. In analyses adjusting for baseline sociodemographics and drug treatment, the risk of using stimulants within 6 months was significantly higher among women who reported recent sexual violence (Adjusted Relative Risk [ARR]=4.31; 95% CI:1.97-9.45), sleeping in a shelter or public place (ARR=2.75; 95% CI:1.15-6.57), and using unprescribed opioid analgesics (ARR=2.54; 95% CI:1.01-6.38).

CONCLUSION

We found that almost half of homeless and unstably housed women used stimulants at baseline and 14% of those who did not use began within 6 months. Addressing homelessness and sexual violence is critical to reduce stimulant use among impoverished women.