DOI: 10.5061/dryad.hdr7sqvkr
title: Differences in neurotoxic outcomes of organophosphorus pesticides revealed via multi-dimensional screening in adult and regenerating planarians

description: Organophosphorus pesticides (OPs) are a chemically diverse class of
 commonly used insecticides. Epidemiological studies suggest that low dose
 chronic prenatal and infant exposures can lead to life-long neurological
 damage and behavioral disorders. While inhibition of acetylcholinesterase
 (AChE) is the shared mechanism of acute OP neurotoxicity, OP-induced
 developmental neurotoxicity (DNT) can occur independently and/or in the
 absence of significant AChE inhibition, suggesting alternative targets.
 Moreover, different OPs can cause different adverse outcomes, suggesting
 that different OPs act through different mechanisms, emphasizing the
 importance of comparative studies of OP toxicity. Freshwater planarians
 are an invertebrate system that uniquely allows for automated, rapid and
 inexpensive testing of adult and developing organisms in parallel to
 differentiate neurotoxicity from DNT. Effects found only in regenerating
 planarians would be indicative of DNT, whereas shared effects may
 represent general neurotoxicity. We leverage this feature to investigate
 potential differential effects of these OPs on the adult and developing
 brain by performing a comparative high-throughput screen to test 7 OPs
 (acephate, chlorpyrifos, dichlorvos, diazinon, malathion, parathion and
 profenofos) across 10 concentrations in quarter-log steps. Neurotoxicity
 was evaluated using a wide range of quantitative morphological and
 behavioral readouts. AChE activity was measured using an Ellman assay. The
 toxicological profiles of the 7 OPs differed across the OPs and between
 adult and regenerating planarians. Toxicological profiles were not
 correlated with levels of AChE inhibition. Twenty-two “mechanistic control
 compounds” known to target pathways suggested in the literature to be
 affected by OPs (cholinergic neurotransmission, serotonin
 neurotransmission, endocannabinoid system, cytoskeleton, adenyl cyclase
 and oxidative stress) and 2 negative controls were also screened. When
 compared with the mechanistic control compounds, the phenotypic profiles
 of the different OPs separated into distinct clusters. The phenotypic
 profiles of adult vs regenerating planarians exposed to the OPs clustered
 differently, suggesting some developmental-specific mechanisms. These
 results further support findings in other systems that OPs cause different
 adverse outcomes in the (developing) brain and build the foundation for
 future comparative studies focused on delineating the mechanisms of OP
 neurotoxicity in planarians.
description: Adult (A) and Regenerating (R) planarians of the species
 <em>Dugesia japonica</em> were screened for a multitude of
 morphological and behavioral endpoints on days 7(d7) and 12 (d12) of
 exposure. Experiments were performed in at least triplicate with n=8 per
 replicate (total n&gt;=24). For binary endpoints (lethality, body
 shape, stickiness, scrunching and eye regeneration), the data are shown as
 the number of planarians affected (n_in) and the total number of
 planarians analyzed (N). For stickiness and scrunching, the incidence
 number (n_in) by normalized by the incidence number of the in-plate
 vehicle controls. For continuous endpoints, the data are provided as the
 normalized response ("resp"), which has been normalized by the
 in-plate vehicle controls. These datasets were used as input for the
 Rcurvep package to calculate the benchmark response and benchmark
 concentration. For more details, please see the corresponding
 publication.
description: Files are named in the format “endpoint_D#WormType” where day (D)
 can be either 7 or 12 and Worm Type is either A (Adult) or R
 (Regenerating). E.g., Resting_D7A contains the individual responses for
 the resting endpoint on day 7 in adult planarians. The
 concentration of each chemical ("conc") is listed in log10
 (molar concentration).  Missing data are shown as
 "NA".