1 Set up

Setting up the R/RStudio environment is out of scope for this CE and attendees are expected to have already done so if they wish to follow along. Download the latest version of R as well as the RStudio integrated development environment (IDE). Check out online resources for more information on installing R and RStudio, e.g. https://rstudio-education.github.io/hopr/starting.html

R packages contain code, data, and documentation in a standardized format that can be installed by users of R. Comprehensive R Archive Network (CRAN) is R’s central software repository for R packages. If new to R, first install packages from CRAN then load packages into your local session. The following packages below were required to create this vignette.

## install packages
install.packages("tcpl", "data.table", "ctxR", "dplyr", "ggplot2", "kableExtra")

## load tcpl and dependency packages
library(tcpl)
library(data.table)
library(ctxR)

## load formatting packages
library(dplyr)
library(ggplot2)
library(kableExtra)

There are a number of resources available on the web for learning R programming and using R in different computing and data science contexts.

2 Introduction to the CompTox Chemicals Dashboard (CCD)

Accessing chemical data is a vital step in many workflows related to chemical, biological, and environmental modeling. While there are many resources available from which one can pull data, the CompTox Chemicals Dashboard (CCD), built and maintained by the United States Environmental Protection Agency, is particularly well-designed and suitable for these purposes. Originally introduced in The CompTox Chemistry Dashboard: a community data resource for environmental chemistry, the CCD contains information on over 1.2 million chemicals as of May 2024 and has been cited 612 times according to CrossRef. To learn more about the CCD, please visit the About CCD page.

The CCD includes chemical information from many different domains, including physicochemical, environmental fate and transport, exposure, usage, in vivo toxicity, and in vitro bioassay data. For information on data sources and current versions, please review the CCD Release Notes. CCD provides a graphical user interface that allows for an interactive user experience and is easy to navigate. As such, users can explore the data available on the CCD without any programming background.

The CCD can be queried for one chemical at a time or using batch search for many chemicals.

2.1 Single Chemical Search

In single-substance search, the user enters a full or partial chemical identifier (name, CASRN, InChiKey, or DSSTox ID) into a search box on the CCD homepage. Autocomplete can provide a list of possible matches. The figure below shows an example: the CCD landing page for the chemical Bisphenol A. This page is generated for Bisphenol A, an example data-rich chemical and focus throughout this vignette. Each chemical represented in the CCD has its own page similar to this, with varying levels of available information.

Bisphenol A CCD landing page

The different domains of data available for this chemical are shown by the tabs on the left side of the page: for example, “Physchem Prop.” (physico-chemical properties), “Env. Fate/Transport” (environmental fate and transport data), and “Hazard Data” (in vivo hazard and toxicity data), among others.

2.2 Bioactivity > ToxCast: Summary

CCD’s ToxCast bioactivity module presents a view of potency and relative efficacy metrics across ToxCast endpoints for chemicals of interest for multi-concentration data only. Single concentration data may also be available for this chemical and can be found in the Dashboard on the individual Assay pages, under List of Assays. All ToxCast associated materials, including the MySQL database, release notes, summary files, assay information and concentration response plots as well as processing package, are available on the data downloads page: https://www.epa.gov/comptox-tools/exploring-toxcast-data.

Summary Plot: In the summary plot, the scaled top value for each chemical by assay endpoint pair is calculated by dividing the maximal modeled response (top) value from the fitted curve by the activity cutoff for that assay endpoint, thereby enabling response comparisons across assay endpoints that originally had different y-axis units. Estimated cytotoxicity median and lower bound threshold values are included to contextualize response values, i.e. where generalized cell death may be confounding bioactivity. The cytotoxicity median and lower bound threshold are based on many cytotoxicity assay endpoints, and so this provides a general context (as described in https://doi.org/10.1093/toxsci/kfw092 and the tcpl manual for function tcplCytoPt: https://cran.r-project.org/web/packages/tcpl/tcpl.pdf) in contrast to more specific context from cytotoxicity assays that may be run in parallel for cell-based assays.

Summary Grid: In the summary grid, all ToxCast data for the given chemical is provided and users can easily sort, filter, and export ToxCast results and assay descriptions. Select the Bioactivity Summary Grid column header ☰ to filter, rearrange, and add additional annotation and potency columns. Assay endpoints specific to a Gene Symbol or Intended Target Family can be identified using the filters by column in the grid.

ToxCast Summary Plot of BPA on CCD

2.3 Batch Chemical Search

In CCD Batch Search, the user enters a list of search inputs, separated by new lines, into a search box. The user selects the type(s) of inputs by selecting one or more checkboxes, i.e. chemical identifiers, monoisotopic masses, or molecular formulas. Then, the user selects “Display All Chemicals” to display the list of substances matching the batch-search inputs, or “Choose Export Options” to choose options for exporting the batch-search results as a spreadsheet. The exported spreadsheet may include data from most of the domains available on an individual substance’s CCD page.

CCD Batch Search

The user can download the selected information in various formats, such as Excel (.xlsx), comma-separated values (.csv), or different types of chemical table files (.e.g, MOL). NOTE: that .xlsx file format is necessary for inclusion of “Enhanced Data Sheets” from Batch Search.

CCD Batch Search Customized Export

The web interface for Batch Search only allows input of 10,000 identifiers at a time. If a user wants to retrieve information for more than 10,000 chemicals, identifiers will need to be separated into multiple batches and searched separately. Users may export ToxCast relevant metadata or enhanced data sheet:

Assay Hit Count: Checking this Assay Hit Count box inserts the number of ToxCast assays that the chemical is tested in as well as the percent of assays for which the chemical is active.

ToxCast Assays: AC50: Selecting this checkbox provides a separate Excel worksheet with concentrations at 50% of maximal activity (uM) across ToxCast endpoints for chemicals listed in input, where responses are deemed active, i.e., continuous hit call value >= 0.9. AC50 values for active hit calls are in arithmetic units. If the activity hit call is considered inactive, AC50 will display as 1e6 (1000000).

2.4 Learning Check Point: CCD Objectives

Users should be able to:

Single Chemical Search > Navigate to ToxCast tab >
- ToxCast Summary plot (AC50 vs Scaled Top (max modeled response/cutoff), cytotoxicity burst median and lower bounds)
- Bioactivity grid (Adding additional fields like Annotations, Inspecting concentration-response plots)
Search by gene
Search by assay name
Lists of Assay vs Chemicals > Send to Batch
Batch Search Export of ToxCast AC50 values for a list of Chemicals

2.5 Challenges of web-based dashboard search

Practicing researchers may follow a workflow that looks something like this:

Start with a dataset that includes your chemical identifiers of interest. These may include chemical names, Chemical Abstract Service Registry Numbers (CASRNs), Distributed Searchable Structure-Toxicity Database (DSSTox) identifiers, or InChIKeys.
Export the chemical identifiers to a spreadsheet. Often, this is done by importing the data into an environment such as R or Python, in order to do some data wrangling (e.g., to select only the unique substance identfiers; to clean up improperly-formatted CASRNs; etc.). Then, the identifiers are saved in a spreadsheet (an Excel, .csv, or .txt file), one chemical identifier per row.
Copy and paste the chemical identifiers from the spreadsheet into the CCD Batch Search box. If there are more than 10,000 total chemical identifiers, divide them into batches of 10,000 or less, and search each batch separately.
Choose your desired export options on the CCD Batch Search page.
Download the exported spreadsheet of CCD data. By default, the downloaded spreadsheet will be given a file name that includes the timestamp of the download.
Repeat steps 3-5 for each batch of 10,000 identifiers produced in step 2.
Import the downloaded spreadsheet(s) of CCD data into the analysis tool you are using (e.g. R or Python).
Merge the table(s) of downloaded CCD data with your original dataset of interest.
Proceed with research-related data analysis using the chemical data downloaded from the CCD (e.g., statistical modeling, visualization, etc.).

Because each of these workflow steps requires manual interaction with the search and download process, the risk of human error inevitably creeps in. Here are a few real-world possibilities (the authors can neither confirm nor deny that they have personally committed any of these errors):

Researchers could copy/paste the wrong identifiers into the CCD batch search, especially if more than 10,000 identifiers need to be divided into separate batches.
Chemical identifiers could be corrupted during the process of exporting to a spreadsheet.
- If a researcher opens and resaves a CSV file using Microsoft Excel, any information that appears to be in date-like format will be automatically converted to a date (unless the researcher has the most recently-updated version of Excel and has selected the option in Settings that will stop Excel from auto-detecting dates). This behavior has long been identified as a problem in genomics, where gene names can appear date-like to Excel (Abeysooriya et al. 2021). It also affects cheminformatics, where chemical identifiers can appear date-like to Excel. For example, the valid CASRN “1990-07-4” would automatically be converted to “07/04/1990” (if Excel is set to use MM/DD/YYYY date formats). CCD batch search cannot recognize “07/04/1990” as a valid chemical identifier and will be unable to return any chemical data.
Researchers could accidentally rename a downloaded CCD data file to overwrite a previous download, e.g. when searching multiple batches of identifiers.
Researchers could mistakenly import the wrong CCD download file back into their analysis environment e.g. when searching multiple batches of identifiers.
In the research product produced, it is unlikely that the date of the files downloaded from CCD, and the version of the data or the version of CCD, will be recorded, limiting the reproducibility of the research product because the source data is not versioned.

Moreover, the manual stages of this kind of workflow are also non-transparent and not easily reproducible. Utilizing APIs for data exploration and retrieval can start to alleviate these concerns.

3 Introduction to CTX APIs

CTX APIs, or Computational Toxicology and Exposure APIs, are Application Programming Interfaces (APIs) that allow users to access data from many of the US EPA’s computational toxicology and exposure resources. These APIs are free to use and are available to the public.

Here are some things to know about CTX APIs:

How to access: Users need a free API key to access the APIs, which can be requested by emailing the CTX admins at ccte_api@epa.gov. An API key identifies the user to the EPA servers and verifies that they have permission to access the database. This is to help us understand who is using data to better serve stakeholder needs!
Where to find: The APIs are hosted on cloud.gov, a secure cloud environment for US federal government applications.
How to use: The APIs use the Hypertext Transfer Protocol (HTTP) to communicate between clients and servers. The CTX API web documentation includes colored boxes next to each endpoint to indicate the type of HTTP method associated with it.
What the data is used for: The data from the CTX APIs can be leveraged in various research applications and user interfaces, such as the CompTox Chemicals Dashboard. The EPA uses the data to evaluate the potential health effects of thousands of chemicals.

The ToxCast Data Analysis Pipeline (tcpl) R Package has been integrated with the Computational Toxicology and Exposure (CTX) APIs) via (ctxR). See tcpl’s vignette for more guidance on data retrieval and plotting capabilities with tcpl.

NOTE: As of Sept 2024, invitrodb v4.1 data is available on the CTX Bioactivity API. Check here for current version information. As of Sept 2024, invitrodb v4.2 data has been released for download but is not currently in the CTX Bioactivity API or the CCD. For this latest version, you can retrieve it here: https://www.epa.gov/comptox-tools/exploring-toxcast-data

3.1 CTX Bioactivity API

The Bioactivity API endpoints are organized into two different resources, “Assay” and “Data”. “Assay” resource endpoints provide assay metadata for specific or all invitrodb ‘aeids’ (assay endpoint ids). These include annotations from invitrodb’s assay, assay_component, assay_component_endpoint, assay_list, assay_source, and gene tables, all returned in a by-aeid format.

“Data” resource endpoints are split into summary data (by ‘aeid’) and bioactivity data by ‘m4id’ (i.e. both ‘aeid’ and ‘spid’). The summary endpoint returns the number of active hits and total multi- and single-concentration chemicals tested for specific ‘aeids’. The other endpoints return chemical information, level 3 concentration-response values, level 4 fit parameters, level 5 hit parameters, and level 6 flags for individual chemicals tested for given ‘AEIDs’, ‘m4ids’, ‘SPIDs’, or ‘DTXSIDs’.

Regular ToxCast/invitrodb users may find it easier to use tcpl, which has integrated ctxR’s bioactivity functions to make the API data retrievable in a familiar format. However, several ctxR functions can be used to access the CTX Bioactivity API data if desired.

For general use of the package, the user may use the function register_ctx_api_key() to store the API key in the current session or more permanently for access across sessions.

## This stores the key in the current session
register_ctx_api_key(key = '<YOUR API KEY>')

## This stores the key across multiple sessions and only needs to be run once. 
## If the key changes, rerun this with the new key.
register_ctx_api_key(key = '<YOUR API KEY>', write = TRUE)

3.1.1 Bioactivity Resource

The function get_bioactivity_details() retrieves all multi-concentration bioactivity data for a given chemical based on input DTXSID. In this example, query for Bisphenol A (BPA), which has DTXSID “DTXSID7020182”

## Load ToxCast data for BPA
bpa_bioactivity <- get_bioactivity_details(DTXSID = 'DTXSID7020182')

Click here to preview the first six rows of bioactivity data available for BPA.

tmpi	m5id	modl	fitc	coff	actp	modelType	chidRep	stkc	stkcUnit	testedConcUnit	logc	resp	pow_a	pow_p	exp2_a	exp2_b	exp3_a	exp3_b	exp3_p	exp5_p	gnls_p	gnls_q	hill_p	pow_er	cnst_er	exp2_er	exp3_er	exp4_er	exp4_ga	exp4_tp	exp5_er	exp5_ga	exp5_tp	gnls_er	gnls_ga	gnls_la	gnls_tp	hill_er	hill_ga	hill_tp	poly1_a	poly2_a	poly2_b	pow_aic	pow_cov	pow_rme	pow_top	cnst_aic	cnst_rme	exp2_aic	exp2_cov	exp2_rme	exp2_top	exp3_aic	exp3_cov	exp3_rme	exp3_top	exp4_aic	exp4_cov	exp4_rme	exp4_top	exp5_aic	exp5_cov	exp5_rme	exp5_top	gnls_aic	gnls_cov	gnls_rme	gnls_top	hill_aic	hill_cov	hill_rme	hill_top	poly1_er	poly2_er	pow_a_sd	pow_ac50	pow_p_sd	all_onesd	exp2_a_sd	exp2_ac50	exp2_b_sd	exp3_a_sd	exp3_ac50	exp3_b_sd	exp3_p_sd	exp4_ac50	exp5_ac50	exp5_p_sd	gnls_ac50	gnls_p_sd	gnls_q_sd	hill_ac50	hill_p_sd	poly1_aic	poly1_cov	poly1_rme	poly1_top	poly2_aic	poly2_cov	poly2_rme	poly2_top	pow_er_sd	exp2_er_sd	exp3_er_sd	exp4_er_sd	exp4_ga_sd	exp4_tp_sd	exp5_er_sd	exp5_ga_sd	exp5_tp_sd	gnls_er_sd	gnls_ga_sd	gnls_la_sd	gnls_tp_sd	hill_er_sd	hill_ga_sd	hill_tp_sd	poly1_a_sd	poly1_ac50	poly2_a_sd	poly2_ac50	poly2_b_sd	poly1_er_sd	poly2_er_sd	pow_success	cnst_success	exp2_success	exp3_success	exp4_success	exp5_success	gnls_success	hill_success	poly1_success	poly2_success	gnls_ac50_loss	p	er	ga	tp	ac5	bmr	mll	top	ac10	ac20	ac50	rmse	caikwt	top_over_cutoff	a	bmd	bmdl	bmdu	ac1sd	q	la	ac50_loss	acc	b	flag	mc6MthdId	aeid	m4id	spid	chid	casn	chnm	dtxsid	bmad	respMax	respMin	maxMean	maxMeanConc	maxMed	maxMedConc	logcMax	logcMin	nconc	npts	nrep
716	4787296	exp5	13	0.0791812	NA	2	0	20.0	mM	uM	1.00000, 0.00000, 1.60206, 0.60206	-0.020, 0.008, -0.049, 0.001	-0.0014428	0.9592987	-4.6448208	3753.223844	-0.0353311	47.31448	0.7860427	7.9999999	7.9999999	2.497212	7.9999995	-5.068015	-3.866838	-5.064046	-4.986425	-5.061595	17.730331	-0.0588000	-6.079040	10.354609	-0.0490002	-6.077958	10.47740	686.7938	-0.0490416	-6.077936	10.47567	-0.0490014	-0.0012439	-6.8404953	5.537761e+03	-21.98427	1	0.0066778	-0.0496647	-15.56073	0.0267675	-21.96011	1	0.0066940	-0.0497669	-19.53428	1	0.0070553	-0.0495371	-21.67067	1	0.0071217	-0.0588000	-25.55154	1	0.0040322	-0.0490002	-21.54910	1	0.0040325	-0.0490120	-25.54909	1	0.0040325	-0.0490014	-5.065595	-5.062728	0.0015788	19.420385	0.2994375	0.1560347	49.9228699	20.05329	4.012005e+04	0.0897782	21.159764	98.94007	0.4298393	17.730331	10.354609	12.4430868	10.47590	NA	NA	10.47567	6.7570679	-23.96775	1	0.0066876	-0.0497550	-21.95744	1	0.0066963	-0.0497667	0.4173604	0.4176039	0.4298381	0.4808176	9.506270	0.0173181	0.6586148	0.5777096	0.0020450	NA	NA	NA	NA	0.6590755	0.4313022	0.0020411	0.0001400	20	64.8364066	20.07171	5.210984e+04	0.4173350	0.4178536	1	1	1	1	1	1	1	1	1	1	687.126	7.9999999	-6.079040	10.35461	-0.0490002	7.478046	0.2104908	16.77577	-0.0490002	8.182109	8.986769	10.354609	0.0040322	0.0067235	0.6188365	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	13, 14	146	392721	TP0000077C05	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	0.0080000	-0.0490000	0.0080000	0.00000	0.0080000	0.00000	1.60206	0.00000	4	4	1
1405	4787985	poly1	13	0.0791812	NA	2	0	20.3	mM	uM	1.60206, 0.30103, 1.00000, 1.60206, 0.69897, 0.30103, 1.00000, 0.69897	-0.0162930040, 0.0009765513, -0.0040055670, -0.0527708230, -0.0084209870, -0.0188779660, -0.0175304400, -0.0142500770	-0.0047526	0.4718645	-6.7732303	6434.987816	-0.0169112	41.98541	0.3580042	0.5638685	0.5897359	6.569511	0.5895251	-4.643124	-4.096128	-4.567034	-4.638488	-4.594978	11.623193	-0.0329091	-4.664331	24.088362	-0.0414382	-4.658047	80.63318	3973.4440	-0.0633250	-4.658091	80.70038	-0.0633250	-0.0010560	-9.3991818	8.932530e+03	-42.06359	1	0.0118185	-0.0270949	-36.63585	0.0223743	-40.94052	1	0.0125351	-0.0422336	-40.12324	1	0.0116245	-0.0282745	-41.59935	1	0.0118204	-0.0329091	-39.96494	1	0.0122098	-0.0414382	-35.96631	0	0.0121691	-0.0544430	-39.96631	1	0.0121700	-0.0633250	-4.566625	-4.566803	0.0049698	9.206645	0.4209828	0.1560347	98.3423031	20.03108	9.320505e+04	NA	10.438421	NA	NA	11.623193	24.088362	0.5653226	49.95301	NA	NA	80.70038	0.6376805	-42.94527	1	0.0125330	-0.0422383	-40.93844	1	0.0125421	-0.0422782	0.3612291	0.3462718	NA	0.3513932	21.949710	0.0413074	0.3646821	110.6663101	0.0761294	NA	NA	NA	NA	0.3650052	550.6860491	0.1509537	0.0003566	20	114.4215999	20.04458	1.082021e+05	0.3462516	0.3464412	1	1	1	1	1	1	1	1	1	1	4040.330	NA	-4.566625	NA	NA	2.000000	0.2104908	23.47263	-0.0422383	4.000000	8.000000	20.000000	0.0125330	0.0409060	0.5334376	-0.0010560	199.3367	141.6199	474.6410	147.7662	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4 , Bmd > ac50, indication of high baseline variability	14, 9	146	393410	TP0000496A08	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	0.0009766	-0.0527708	-0.0089507	0.30103	-0.0089507	0.30103	1.60206	0.30103	4	8	2
1423	4788003	pow	13	0.0791812	NA	2	1	20.3	mM	uM	1.60206, 0.30103, 1.00000, 0.69897, 0.30103, 1.00000, 0.69897, 1.60206	-0.058351750, -0.022358924, -0.025285470, -0.022031331, -0.018866405, -0.035500716, -0.006874923, -0.021082722	-0.0139307	0.3000000	-12.3832514	9679.864437	-0.0434129	105.87011	0.3000011	0.3641961	0.3831522	7.890175	0.3831893	-4.648191	-3.627362	-4.108325	-4.615223	-4.659977	1.529477	-0.0279641	-4.653095	5.845479	-0.0476607	-4.651029	32.87705	3754.6495	-0.0700221	-4.651011	32.87115	-0.0700221	-0.0012817	-18.0726077	1.414194e+04	-42.21215	1	0.0114495	-0.0421299	-30.51788	0.0298697	-34.46179	1	0.0178031	-0.0512770	-40.02269	1	0.0121238	-0.0481957	-41.11048	1	0.0132999	-0.0279641	-40.14713	1	0.0115997	-0.0476607	-36.15238	0	0.0115622	-0.0576111	-40.15238	1	0.0115621	-0.0700221	-4.109078	-4.108627	0.0069597	3.968503	0.2533258	0.1560347	143.2676220	20.02066	1.116325e+05	0.1000142	6.939221	538.72442	0.1906033	1.529477	5.845479	0.4361952	12.90624	NA	NA	32.87115	0.5388169	-36.46933	1	0.0177949	-0.0512669	-34.45904	1	0.0178048	-0.0512623	0.3323388	0.3046685	0.3661416	0.4087137	2.387444	0.0096831	0.3447170	38.8186464	0.0786779	NA	NA	NA	NA	0.3418461	382.4619541	0.1713404	0.0003754	20	179.3710746	20.02820	1.398150e+05	0.3045941	0.3045916	1	1	1	1	1	1	1	1	1	1	3796.678	0.3000000	-4.648191	NA	NA	NA	0.2104908	24.10608	-0.0421299	NA	NA	3.968503	0.0114495	0.0028798	0.5320695	-0.0139307	NA	NA	NA	NA	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4	14	146	393428	TP0000498A08	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	-0.0068749	-0.0583518	-0.0144531	0.69897	-0.0144531	0.69897	1.60206	0.30103	4	8	2
1434	4788014	pow	13	0.0791812	NA	2	0	20.3	mM	uM	1.00000, 0.69897, 0.69897, 1.60206, 0.30103, 1.00000, 1.60206, 0.30103	-0.042423830, -0.018199127, -0.039300120, -0.070243575, -0.034689017, -0.026189076, -0.042190440, -0.004385219	-0.0159883	0.3399982	-17.0130357	10522.355008	-0.0392648	52.20333	0.3000006	0.5499441	0.6323059	5.781948	0.6345849	-4.418804	-3.324452	-3.988125	-4.372431	-4.402534	5.466988	-0.0541936	-4.416659	8.256625	-0.0674604	-4.416469	15.48482	1175.5642	-0.0842923	-4.417604	15.44867	-0.0842923	-0.0016196	-23.9969775	1.486670e+04	-39.90897	1	0.0123060	-0.0560401	-25.88774	0.0392080	-32.28963	1	0.0206072	-0.0647970	-37.67170	1	0.0125742	-0.0595805	-39.22067	1	0.0131935	-0.0541936	-37.84524	1	0.0123777	-0.0674604	-33.83603	1	0.0123897	-0.0753860	-37.83597	1	0.0123894	-0.0842923	-3.989664	-3.989254	0.0073330	5.208024	0.1590385	0.1560347	190.3152226	20.01901	1.174087e+05	0.0735880	7.764359	205.40892	0.1915197	5.466988	8.256625	0.4903405	11.07184	0.6959329	20835.5099	15.44867	0.7135147	-34.29770	1	0.0205975	-0.0647854	-32.28631	1	0.0206107	-0.0647394	0.2844967	0.3081117	0.2965407	0.2975840	3.362452	0.0138993	0.2856747	20.4895366	0.0585480	0.2858832	61.01501	14317870	0.0991375	0.2856987	62.2552443	0.1016970	0.0003563	20	226.2142000	20.02683	1.397848e+05	0.3079642	0.3079437	1	1	1	1	1	1	1	1	1	1	1195.421	0.3399982	-4.418804	NA	NA	NA	0.2104908	22.95449	-0.0560401	NA	NA	5.208024	0.0123060	0.0009014	0.7077452	-0.0159883	NA	NA	NA	NA	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4	14	146	393439	TP0000499A10	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	-0.0043852	-0.0702436	-0.0195371	0.30103	-0.0195371	0.30103	1.60206	0.30103	4	8	2
716	4789331	poly1	13	0.0791812	NA	2	0	20.0	mM	uM	0.60206, 1.60206, 0.00000, 1.00000	-0.004, -0.026, 0.019, -0.001	-0.0000210	1.9298414	-0.0016851	14.292354	-0.0150948	39.97355	1.5616831	2.5720118	3.4353461	4.245239	3.4375239	-5.105207	-4.269141	-5.119732	-5.111167	-4.784525	23.483014	-0.0312000	-5.098243	27.687923	-0.0312000	-5.094068	25.08753	1084.0390	-0.0312000	-5.094090	25.09852	-0.0312000	-0.0006208	-0.0001298	2.930628e+00	-20.32558	1	0.0096963	-0.0259813	-19.19290	0.0162327	-20.34607	1	0.0097224	-0.0259890	-18.33919	1	0.0096996	-0.0259795	-18.87484	1	0.0107752	-0.0312000	-18.30678	1	0.0096990	-0.0312000	-14.29357	1	0.0097036	-0.0311514	-18.29357	1	0.0097036	-0.0312000	-4.957939	-5.109174	0.0002462	27.930138	3.1772449	0.1748452	0.0095168	30.93808	2.714077e+01	0.6055772	29.459402	649.28415	8.3282625	23.483014	27.687923	6.2508295	25.06480	17.4516974	5629.6852	25.09852	16.5873187	-21.67413	1	0.0101951	-0.0248308	-20.32728	1	0.0097082	-0.0259481	0.5904399	0.6019969	0.6169114	0.5241570	26.510136	0.0238649	0.5875827	83.9234059	0.1094183	0.5865875	122.93077	4740412	0.1292349	0.5863450	116.3790611	0.1223919	0.0001549	20	0.0013238	27.87339	1.549231e+01	0.5361260	0.5925829	1	1	1	1	1	1	1	1	1	1	1084.834	NA	-4.957939	NA	NA	2.000000	0.2358661	12.83706	-0.0248308	4.000000	8.000000	20.000000	0.0101951	0.2243287	0.3135943	-0.0006208	379.9576	263.9718	750.4563	281.6587	NA	NA	NA	NA	NA	Average number of replicates per conc is less than 2, Bmd > ac50, indication of high baseline variability , Number of concentrations tested is less than 4	13, 9, 14	148	394756	TP0000077C05	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0257590	0.0190000	-0.0260000	0.0190000	0.00000	0.0190000	0.00000	1.60206	0.00000	4	4	1
1405	4790020	poly1	13	0.0791812	NA	2	0	20.3	mM	uM	1.60206, 0.30103, 1.60206, 0.69897, 0.30103, 1.00000, 1.00000, 0.69897	-0.0195828230, -0.0065298300, -0.0368289760, -0.0094431750, -0.0198203400, 0.0202787030, -0.0003974539, 0.0159239450	0.0000000	7.4669657	-0.0000014	4.023976	-0.0190818	40.49855	7.8399712	7.9999918	7.9468189	1.503535	7.9520649	-4.441523	-4.078191	-4.441933	-4.441199	-4.322145	28.545146	-0.0338471	-4.441346	34.189416	-0.0309185	-4.441518	36.07627	3466.8814	-0.0406638	-4.441393	37.24481	-0.0441948	-0.0006259	-0.0000004	1.430626e-01	-39.66564	1	0.0129343	-0.0282016	-37.65645	0.0191359	-39.66287	1	0.0129370	-0.0281575	-37.66576	1	0.0129342	-0.0282031	-37.41739	1	0.0151599	-0.0338471	-37.66559	1	0.0129343	-0.0309185	-33.66552	1	0.0129344	-0.0404684	-37.66557	1	0.0129344	-0.0441948	-4.365286	-4.479115	0.0000004	36.453992	0.0861014	0.1748452	0.0000016	37.21099	1.307239e-01	NA	37.553893	NA	NA	28.545146	34.189416	82.7038416	36.04208	75.8717424	271.3305	37.24481	NA	-40.13079	1	0.0145042	-0.0250370	-39.24680	1	0.0133075	-0.0275892	0.3020025	0.3019179	NA	0.3184006	34.869636	0.0304292	0.3019906	359.2796286	0.6586123	0.3019695	272.42214	2782192	0.8085816	NA	NA	NA	0.0002342	20	0.0000011	28.26337	2.302960e-02	0.3106562	0.2973885	1	1	1	1	1	1	1	1	1	1	3489.111	NA	-4.365286	NA	NA	2.000000	0.2358661	22.06539	-0.0250370	4.000000	8.000000	20.000000	0.0145042	0.2249296	0.3161988	-0.0006259	376.8280	232.5859	1104.4237	279.3387	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4 , Bmd > ac50, indication of high baseline variability	14, 9	148	395445	TP0000496A08	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0257590	0.0202787	-0.0368290	0.0099406	1.00000	0.0099406	1.00000	1.60206	0.30103	4	8	2

Using a different input, get_bioactivity_details() can also be used to retrieve all multi-concentration bioactivity data for a given endpoint, based on input AEID (assay endpoint identifier). Let’s consider assay endpoint id 146.

## Load ToxCast data for endpoint 146
assay_id_search <- get_bioactivity_details(AEID = 146)

Click here to preview six rows of bioactivity data available for assay endpoint 146.

tmpi	m5id	modl	hitc	fitc	coff	actp	modelType	chidRep	stkc	stkcUnit	testedConcUnit	logc	resp	pow_a	pow_p	exp2_a	exp2_b	exp3_a	exp3_b	exp3_p	exp5_p	gnls_p	gnls_q	hill_p	pow_er	cnst_er	exp2_er	exp3_er	exp4_er	exp4_ga	exp4_tp	exp5_er	exp5_ga	exp5_tp	gnls_er	gnls_ga	gnls_la	gnls_tp	hill_er	hill_ga	hill_tp	poly1_a	poly2_a	poly2_b	pow_aic	pow_cov	pow_rme	pow_top	cnst_aic	cnst_rme	exp2_aic	exp2_cov	exp2_rme	exp2_top	exp3_aic	exp3_cov	exp3_rme	exp3_top	exp4_aic	exp4_cov	exp4_rme	exp4_top	exp5_aic	exp5_cov	exp5_rme	exp5_top	gnls_aic	gnls_cov	gnls_rme	gnls_top	hill_aic	hill_cov	hill_rme	hill_top	poly1_er	poly2_er	pow_a_sd	pow_ac50	pow_p_sd	all_onesd	exp2_a_sd	exp2_ac50	exp2_b_sd	exp3_a_sd	exp3_ac50	exp3_b_sd	exp3_p_sd	exp4_ac50	exp5_ac50	exp5_p_sd	gnls_ac50	gnls_p_sd	gnls_q_sd	hill_ac50	hill_p_sd	poly1_aic	poly1_cov	poly1_rme	poly1_top	poly2_aic	poly2_cov	poly2_rme	poly2_top	pow_er_sd	exp2_er_sd	exp3_er_sd	exp4_er_sd	exp4_ga_sd	exp4_tp_sd	exp5_er_sd	exp5_ga_sd	exp5_tp_sd	gnls_er_sd	gnls_ga_sd	gnls_la_sd	gnls_tp_sd	hill_er_sd	hill_ga_sd	hill_tp_sd	poly1_a_sd	poly1_ac50	poly2_a_sd	poly2_ac50	poly2_b_sd	poly1_er_sd	poly2_er_sd	pow_success	cnst_success	exp2_success	exp3_success	exp4_success	exp5_success	gnls_success	hill_success	poly1_success	poly2_success	gnls_ac50_loss	a	p	er	ac5	bmd	bmr	mll	top	ac10	ac20	ac50	bmdl	bmdu	rmse	ac1sd	caikwt	hitcall	top_over_cutoff	b	acc	ga	tp	q	la	ac50_loss	flag	mc6MthdId	aeid	m4id	spid	chid	casn	chnm	dtxsid	bmad	respMax	respMin	maxMean	maxMeanConc	maxMed	maxMedConc	logcMax	logcMin	nconc	npts	nrep
1	4786581	pow	0.0000000	13	0.0791812	NA	2	0	20	mM	uM	0.9542425, 0.4771213, 0.0000000, 1.4771213	-0.001480822, -0.002563255, -0.002034287, 0.021769969	0.0000000	8.0125928	0.0000001	2.470937	0.0025060	26.59934	6.8172277	7.973673	8.000000	3.4185233	7.999961	-6.390228	-5.1279488	-6.390936	-6.390347	-5.215022	21.167721	0.0261240	-6.389569	26.6316222	0.0261239	-6.388683	24.535595	2978.8579	0.0261240	-6.388624	24.5356040	0.0261240	0.0006668	0.0000000	0.0193999	-32.52113	1	0.0017962	0.0217684	-23.351422	0.0110321	-32.51743	1	0.0017969	0.0217655	-30.52096	1	0.0017962	0.0217733	-23.229130	1	0.0056835	0.0261240	-30.51919	1	0.0017966	0.0261239	-26.513245	1	0.0017977	0.0261235	-30.51324	1	0.0017977	0.0261240	-5.466858	-6.081291	0.0000006	27.513868	0.0301072	0.1560347	0.0000014	28.28729	1.554830e-02	NA	28.69256	NA	NA	21.167721	26.6316222	25.8672932	24.535480	15.93627	9277.402	24.5356040	15.9284642	-27.01299	1	0.0046696	0.0200029	-30.06790	1	0.0024358	0.0215460	0.4205928	0.4213698	NA	0.4626810	19.2340288	0.0196127	0.4206191	17.4802864	0.0698468	0.4253872	10.64875	37144089	0.0251744	0.4253906	10.6443410	0.0251593	0.0001349	15	0.0000008	21.21036	9.237000e-04	0.4322381	0.4191065	1	1	1	1	1	1	1	1	1	1	2978.8906	0.0000000	8.012593	-6.390228	20.6418252	39.82020	0.2104908	19.26056	0.0217684	22.5070050	24.5407211	27.51387	39.21448	40.52157	0.0017962	38.35990	0.0101022	0.0000000	0.2749188	NA	NA	NA	NA	NA	NA	NA	Bmd > ac50, indication of high baseline variability , Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	9, 13, 14	146	392006	1210314457	892443	2806-15-7	Sodium perfluorodecanesulfonate	DTXSID60892443	0.0227491	0.0217700	-0.0025633	0.0217700	1.477121	0.0217700	1.477121	1.477121	0.00000	4	4	1
2	4786582	poly2	0.9999992	42	0.0791812	NA	2	0	30	mM	uM	0.845098, 1.301030, 0.301030, 1.778151	-0.070258416, -0.255427870, 0.006490851, -1.252998400	-0.0034804	1.4375824	-0.4561853	45.421404	-1.3984346	86.61881	1.2165920	2.047674	2.897449	7.6893591	2.897450	-4.699353	-0.8984087	-4.689525	-5.080423	-1.817028	35.823915	-1.5035981	-4.345736	37.7636381	-1.5035981	-4.136759	34.478861	5936.3367	-1.5035981	-4.136755	34.4788519	-1.5035981	-0.0202851	-0.3668273	42.4120788	-18.68631	1	0.0104245	-1.2527648	9.235886	0.6403567	-17.30967	1	0.0139008	-1.2531541	-17.78784	1	0.0105423	-1.2529708	4.017042	1	0.1721837	-1.5035981	-12.61649	1	0.0193847	-1.5035981	-6.035649	0	0.0280231	-1.5035448	-10.03565	1	0.0280231	-1.5035981	-2.561102	-5.074494	0.0000256	37.046832	0.0039959	0.1560347	0.0031830	39.26097	2.088259e-01	0.0074393	38.26998	0.3321145	0.0080893	35.823915	37.7636381	0.0628293	34.478018	NA	NA	34.4788519	0.1079174	-3.62743	1	0.0883623	-1.2171067	-18.80750	1	0.0123110	-1.2530977	0.4506082	0.5556919	0.6299482	0.5398363	22.8264679	0.7813928	0.5695792	0.5699134	0.0219467	NA	NA	NA	NA	0.6628952	0.6998570	0.0230703	0.0012578	30	0.0018722	38.14089	1.638130e-01	0.4437396	0.7703037	1	1	1	1	1	1	1	1	1	1	5936.3909	-0.3668273	NA	-5.074494	6.3063640	17.28896	0.2104908	12.40375	-1.2530977	11.4155574	19.7651828	38.14089	17.19925	17.37922	0.0123110	13.64840	0.0000008	0.9999992	15.8256877	42.41208	7.741698	NA	NA	NA	NA	NA	Less than 50% efficacy , Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	17, 13, 14	146	392007	1210314462	379721	2264-01-9	1H,1H,6H,6H-Perfluorohexane-1,6-diol diacrylate	DTXSID80379721	0.0227491	0.0064909	-1.2529984	0.0064909	0.301030	0.0064909	0.301030	1.778151	0.30103	4	4	1
3	4786583	poly1	0.0000000	13	0.0791812	NA	2	0	30	mM	uM	1.301030, 0.845098, 0.301030, 1.778151	-0.011810144, -0.005167083, 0.006786961, -0.001329999	-0.0014352	0.3000000	-0.2375612	3793.986464	-0.0031065	79.75032	0.3000065	7.999702	6.665641	0.7622325	7.999964	-5.128673	-5.0238463	-5.065897	-5.112091	-5.232791	4.607925	-0.0059388	-5.345668	6.3334303	-0.0065697	-5.420323	6.415949	202.8901	-0.0090130	-5.345672	5.9502366	-0.0065719	-0.0000633	-0.2014930	3389.9717091	-22.42629	1	0.0063500	-0.0049018	-25.442392	0.0073145	-21.87218	1	0.0068478	-0.0037868	-20.32090	1	0.0064241	-0.0046743	-23.272647	1	0.0057078	-0.0059388	-22.23201	1	0.0050246	-0.0065697	-18.771607	1	0.0047283	-0.0079575	-22.23152	1	0.0050249	-0.0065719	-5.064136	-5.066297	0.0031726	5.952755	0.5626814	0.1560347	4.3651553	30.11861	6.859992e+04	0.0159137	11.61073	862.7261643	0.9791490	4.607925	6.3334303	75.5720570	6.311938	NA	NA	5.9502366	44.1594957	-23.87527	1	0.0068443	-0.0037993	-21.86795	1	0.0068594	-0.0036294	0.4236958	0.4246747	0.4336333	0.4200032	5.5494497	0.0044213	0.4154584	6.2878603	0.0046983	NA	NA	NA	NA	0.4154644	6.3949199	0.0046898	0.0000993	30	2.6026638	30.26085	4.401981e+04	0.4249240	0.4253428	1	1	1	1	1	1	1	1	1	1	276.2592	-0.0000633	NA	-5.064136	3.0000000	3324.11814	0.2104908	13.93764	-0.0037993	6.0000000	12.0000000	30.00000	740.44403	NA	0.0068443	2464.13502	0.6864469	0.0000000	0.0479828	NA	NA	NA	NA	NA	NA	NA	Bmd > ac50, indication of high baseline variability , Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	9, 13, 14	146	392008	1210314463	194615	4180-26-1	1H,1H,9H-Perfluorononyl acrylate	DTXSID00194615	0.0227491	0.0067870	-0.0118101	0.0067870	0.301030	0.0067870	0.301030	1.778151	0.30103	4	4	1
4	4786584	exp5	1.0000000	42	0.0791812	NA	2	1	30	mM	uM	1.778151, 0.845098, 1.301030, 0.301030	-1.31150340, -0.06231948, -0.33237708, -0.00653846	-0.0071508	1.2730815	-0.9859215	70.903548	-85.6072880	1625.99017	1.2685112	1.837040	2.653020	7.6139726	2.653386	-4.473250	-0.7913534	-3.914530	-4.460883	-1.873418	34.901073	-1.5738041	-5.919333	35.7908257	-1.5738041	-4.500113	32.774866	3503.2400	-1.5738041	-4.503396	32.7691430	-1.5738041	-0.0213585	-1.1670589	89.2304918	-16.84086	1	0.0132910	-1.3124578	9.816643	0.6772079	-12.32817	1	0.0234064	-1.3120838	-14.73526	1	0.0134539	-1.3124554	3.513427	1	0.1607464	-1.5738041	-24.62091	1	0.0044653	-1.5738041	-9.244881	0	0.0185225	-1.5735202	-13.24457	1	0.0185236	-1.5738041	-2.751389	-3.971020	0.0000629	34.809156	0.0040765	0.1560347	0.0179501	36.16586	8.963198e-01	0.7517882	34.84507	11.5671240	0.0037828	34.901073	35.7908257	0.0110556	32.770410	NA	NA	32.7691430	0.0626243	-5.40073	1	0.0685497	-1.2815087	-12.86700	1	0.0216983	-1.3124266	0.4485116	0.4507880	0.4452619	0.5479037	21.3379040	0.7705117	0.6296245	0.1308211	0.0052220	NA	NA	NA	NA	0.6317275	0.4399943	0.0140766	0.0010265	30	0.0198155	35.80512	1.107124e+00	0.4243834	0.4433945	1	1	1	1	1	1	1	1	1	1	3503.4022	NA	1.837040	-5.919333	8.6743187	15.19064	0.2104908	16.31045	-1.5738041	12.8354128	19.3116024	35.79083	15.12601	15.25563	0.0044653	12.77231	0.0000000	1.0000000	19.8759701	NA	8.704514	35.79083	-1.5738041	NA	NA	NA	Less than 50% efficacy , Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	17, 13, 14	146	392009	1210314467	379721	2264-01-9	1H,1H,6H,6H-Perfluorohexane-1,6-diol diacrylate	DTXSID80379721	0.0227491	-0.0065385	-1.3115034	-0.0065385	0.301030	-0.0065385	0.301030	1.778151	0.30103	4	4	1
5	4786585	exp4	0.0000000	13	0.0791812	NA	2	1	30	mM	uM	1.301030, 0.845098, 0.301030, 1.778151	0.018372728, -0.001430542, 0.020026820, 0.018612841	0.0058769	0.3000000	2.2233904	6271.805464	0.0125654	66.08219	0.3000020	1.627375	5.762975	3.6499593	6.834475	-4.815071	-4.7039154	-4.625669	-4.781388	-5.146298	0.200000	0.0172009	-5.147252	0.2376505	0.0171991	-5.147265	0.200000	5999.4901	0.0171992	-5.147270	0.2004545	0.0171992	0.0003562	3.0968756	8757.3799867	-19.75324	1	0.0090062	0.0200721	-16.624974	0.0164857	-18.04049	1	0.0114362	0.0213724	-17.45790	1	0.0093515	0.0206294	-20.560216	1	0.0094681	0.0172009	-18.56354	1	0.0094662	0.0171991	-14.563530	1	0.0094662	0.0171992	-18.56354	1	0.0094662	0.0171992	-4.627004	-4.625577	NA	5.952754	NA	0.1560347	32.2304044	30.07175	9.041326e+04	NA	11.99383	NA	NA	0.200000	0.2376505	NA	0.200000	667.99179	3000.504	0.2004545	2467.5944974	-20.04531	1	0.0114302	0.0213708	-18.03845	1	0.0114390	0.0213632	NA	0.4521090	NA	0.6945552	0.8372202	0.0037167	NA	NA	NA	0.6947704	53.32599	22783702	0.0037121	0.6947718	166.4405381	0.0037121	0.0001466	30	37.9244716	30.10207	1.064481e+05	0.4519259	0.4521476	1	1	1	1	1	1	1	1	1	1	5999.4901	NA	NA	-5.146298	0.0148001	NA	0.2104908	13.28011	0.0172009	0.0304006	0.0643856	0.20000	NA	NA	0.0094681	NA	0.1226447	0.0000000	0.2172351	NA	NA	0.20000	0.0172009	NA	NA	NA	Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	13, 14	146	392010	1210314470	108559	62037-80-3	Ammonium perfluoro-2-methyl-3-oxahexanoate	DTXSID40108559	0.0227491	0.0200268	-0.0014305	0.0200268	0.301030	0.0200268	0.301030	1.778151	0.30103	4	4	1
6	4786586	poly1	0.0000000	13	0.0791812	NA	2	0	30	mM	uM	1.301030, 0.301030, 1.778151, 0.845098	0.003245117, -0.009243081, 0.002971467, 0.006367412	0.0007578	0.3989088	0.2246532	3467.471943	0.0028401	64.11300	4.9796674	7.999991	7.994584	0.6584067	8.000000	-5.407266	-5.1915838	-5.325140	-5.255187	-5.507630	3.572414	0.0036485	-5.695721	5.0424996	0.0041371	-5.805463	3.815568	120.6589	0.0057212	-5.690555	3.8510732	0.0041356	0.0000657	0.1930213	3013.9736770	-23.92925	1	0.0056693	0.0038803	-26.892849	0.0060278	-23.66154	1	0.0056459	0.0039212	-21.26145	1	0.0058407	0.0029877	-24.375186	1	0.0055327	0.0036485	-23.65093	1	0.0048114	0.0041371	-20.026506	1	0.0047345	0.0049244	-23.62159	1	0.0048250	0.0041356	-5.327226	-5.326333	0.0022196	10.556443	0.7581634	0.1560347	4.5214590	30.12978	6.933602e+04	NA	53.93063	NA	NA	3.572414	5.0424996	33.8601445	3.766718	NA	NA	3.8510732	13.0269648	-25.66410	1	0.0056447	0.0039416	-23.65837	1	0.0056473	0.0039190	0.4950916	0.4506043	NA	0.5245560	6.6051577	0.0025111	0.5266723	9.2000784	0.0018706	NA	NA	NA	NA	0.5276939	3.9242803	0.0018875	0.0000699	30	2.6564097	30.29275	4.063818e+04	0.4503765	0.4503601	1	1	1	1	1	1	1	1	1	1	184.7137	0.0000657	NA	-5.327226	3.0000000	3204.17724	0.2104908	14.83205	0.0039416	6.0000000	12.0000000	30.00000	1038.88793	NA	0.0056447	2375.22405	0.6489382	0.0000000	0.0497789	NA	NA	NA	NA	NA	NA	NA	Bmd > ac50, indication of high baseline variability , Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	9, 13, 14	146	392011	1210314471	108559	62037-80-3	Ammonium perfluoro-2-methyl-3-oxahexanoate	DTXSID40108559	0.0227491	0.0063674	-0.0092431	0.0063674	0.845098	0.0063674	0.845098	1.778151	0.30103	4	4	1

Several ctxR functions are used to access the CTX Bioactivity API data, however regular ToxCast/invitrodb users may find it easier to use tcpl, which has integrated ctxR’s bioactivity functions to make the API data retrievable in a familiar format. For the remainder of the vignette, explore how to leverage tcpl’s new API integration.

4 Introduction to tcpl API Integration

The ToxCast Data Analysis Pipeline (tcpl) is an R package that manages, curve-fits, plots, and stores ToxCast data to populate its linked MySQL database, invitrodb. To support different ToxCast data retrieval needs, there are a number of tcpl functions that can be used to query the API and return information to a local R environment. Abbreviations may be used to refer to processing steps or data. Single-concentration “SC” assay data is not currently available via API. “MC” describes multiple-concentration assay data. A particular data or processing level is indicated by appending the level id/number to the end of the SC or MC designation. For example, multiple concentration data from level 3 processing uses the abbreviation MC3.

After loading tcpl library, the function tcplConf is used to establish connection to a database server or the API.

NOTE: When tcpl is loaded, the default configuration sets the options to tcpl’s application API key to support new users testing out the package. This default API key is not intended for regular users; instead, it is highly recommended to obtain a personal API key to also access other CTX APIs. For this, send an email request to CTX API support at ccte_api@epa.gov.

## Install the latest version of tcpl available on CRAN
install.packages('tcpl')

## Advanced users may consider installing the 'dev'branch of tcpl from GitHub for latest features
devtools::install_git('https://github.com/USEPA/CompTox-ToxCast-tcpl.git', branch="dev", force=TRUE)

## Load the tcpl library
library(tcpl) 

## Establish connection. While a typical database connection requires 5 parameters to be provided, 
## using an API connection requires the user to only specify password (`pass`) and driver (`drvr`):
tcplConf(pass = "API key provided by emailing CTX API support at ccte_api@epa.gov",
         drvr = "API")

Every time the package is loaded in a new R session, a message similar to the following will print showing the default package settings:

tcpl (v3.1.0) loaded with the following settings:
  TCPL_DB:    NA
  TCPL_USER:  NA
  TCPL_HOST:  https://api-ccte.epa.gov/bioactivity
  TCPL_DRVR:  API
Default settings stored in tcpl config file. See ?tcplConf for more information.

4.1 Assay Elements

The tcplLoadAsid, tcplLoadAid, tcplLoadAcid, and tcplLoadAeid functions load relevant identifers and names for the respective assay elements based on the user specified parameters whether user has database or API connection.

4.2 Assay Information

Assay source, assay, assay component, and assay endpoint are registered via tcpl scripting into a collection of database tables within invitrodb. For the API, these tables were joined to create a singular “assay” annotations view, which can be returned using tcplQueryAPI.

## Load all ToxCast assay information
assays <- tcplQueryAPI(resource = "assay")

Click here to preview the first six rows of ToxCast assay annotations.

aeid	assay_component_endpoint_name	export_ready	internal_ready	assay_component_endpoint_desc	assay_function_type	normalized_data_type	key_positive_control	signal_direction	intended_target_type	intended_target_type_sub	intended_target_family	intended_target_family_sub	data_usability	acid	assay_component_name	assay_component_desc	assay_component_target_desc	parameter_readout_type	assay_design_type	assay_design_type_sub	biological_process_target	detection_technology_type	detection_technology_type_sub	detection_technology	key_assay_reagent_type	key_assay_reagent	technological_target_type	technological_target_type_sub	aid	assay_name	assay_desc	timepoint_hr	organism_id	organism	tissue	cell_format	cell_free_component_source	cell_short_name	cell_growth_mode	assay_footprint	assay_format_type	assay_format_type_sub	content_readout_type	dilution_solvent	asid	assay_source_name	assay_source_long_name	assay_source_desc	gene	assay_list	citations
2574	ERF_CR_ENZ_hELANE	1	1	Data from the assay component ERF_CR_ENZ_hELANE was analyzed at the assay endpoint, ERF_CR_ENZ_hELANE, in the positive analysis fitting direction relative to DMSO as the negative control and baseline of activity. Using a type of enzyme reporter, loss-of-signal activity can be used to understand changes in enzymatic activity as they relate to gene ELANE. To generalize the intended target to other relatable targets, this assay endpoint is annotated to the protease intended target family, where the subfamily is serine peptidase.	enzymatic activity	percent_activity	3’,4’dichloroisocoumarin	loss	protein	enzyme	protease	serine peptidase	1	2527	ERF_CR_ENZ_hELANE	ERF_CR_ENZ_hELANE is an assay component calculated from the ERF_CR_ENZ_hELANE assay. It is designed to measure enzyme activity using a type of enzyme reporter as detected by absorbance with spectrophotometry technology.	Changes in absorbance produced from the regulation of catalytic activity reaction involving the key substrate, MeO-Suc-Ala-Ala-Pro-Val-p-Nitroanilide, are indicative of changes in enzyme function and kinetics related to the gene ELANE.	single	enzyme reporter	enzyme activity	regulation of catalytic activity	Colorimetric	Absorbance	spectrophotometry	substrate	MeO-Suc-Ala-Ala-Pro-Val-p-Nitroanilide	protein	enzyme	729	ERF_CR_ENZ_hELANE	ERF_CR_ENZ_hELANE is a biochemical, single-readout assay that uses extracted gene-proteins in a cell-free assay. Measurements were taken 0.5 hour after chemical dosing in a 96-well plate. See Neutrophil Elastase Human Chymotrypsin Serine Peptidase Enzymatic Assay, Cerep.	0.50	9606	human	NA	cell-free	human neutrophils	NA	NA	microplate: 96-well plate	biochemical	protein single format	single	DMSO	28	ERF	Eurofins	Eurofins is an international group of laboratories headquartered in Luxembourg, providing testing and support services to the pharmaceutical, food, environmental, agriscience and consumer products industries and to governments.	111 , elastase, neutrophil expressed, NA , ELANE , 1 , live , 1991 , ELANE , elastase, neutrophil expressed, P08246	NA, NA	NA, NA, NA, NA, NA, NA, NA, NA, NA
2575	ERF_CR_ENZ_hEPHA1	1	1	Data from the assay component ERF_CR_ENZ_hEPHA1 was analyzed at the assay endpoint, ERF_CR_ENZ_hEPHA1, in the positive analysis fitting direction relative to DMSO as the negative control and baseline of activity. Using a type of enzyme reporter, loss-of-signal activity can be used to understand changes in enzymatic activity as they relate to gene EPHA1. To generalize the intended target to other relatable targets, this assay endpoint is annotated to the kinase intended target family, where the subfamily is receptor tyrosine kinase.	enzymatic activity	percent_activity	staurosporine	loss	protein	enzyme	kinase	receptor tyrosine kinase	1	2528	ERF_CR_ENZ_hEPHA1	ERF_CR_ENZ_hEPHA1 is an assay component calculated from the ERF_CR_ENZ_hEPHA1 assay. It is designed to measure enzyme activity using a type of enzyme reporter as detected by fluorescence intensity with HTRF technology.	Changes in fluorescence intensity produced from the regulation of catalytic activity reaction involving the key substrate, ATP + biotinyl-beta Abeta Abeta AAEEEIYEEIEAKKK, are indicative of changes in receptor function and kinetics related to the gene EPHA1.	single	enzyme reporter	enzyme activity	regulation of catalytic activity	Fluorescence	Fluorescence intensity	HTRF	substrate	ATP + biotinyl-beta Abeta Abeta AAEEEIYEEIEAKKK	protein	receptor	731	ERF_CR_ENZ_hEPHA1	ERF_CR_ENZ_hEPHA1 is a biochemical, single-readout assay that uses extracted gene-proteins in a cell-free assay. Measurements were taken 0.5 hour after chemical dosing in a 96-well plate. See EphA1 Human RTK Kinase Enzymatic HTRF Assay [Km ATP], Cerep.	0.50	9606	human	NA	cell-free	human recombinant insect cells	NA	NA	microplate: 96-well plate	biochemical	protein single format	single	DMSO	28	ERF	Eurofins	Eurofins is an international group of laboratories headquartered in Luxembourg, providing testing and support services to the pharmaceutical, food, environmental, agriscience and consumer products industries and to governments.	113 , EPH receptor A1, NA , EPHA1 , 1 , live , 2041 , EPHA1 , EPH receptor A1, P21709	NA, NA	NA, NA, NA, NA, NA, NA, NA, NA, NA
2576	ERF_CR_ENZ_hEPHA2	1	1	Data from the assay component ERF_CR_ENZ_hEPHA2 was analyzed at the assay endpoint, ERF_CR_ENZ_hEPHA2, in the positive analysis fitting direction relative to DMSO as the negative control and baseline of activity. Using a type of enzyme reporter, loss-of-signal activity can be used to understand changes in enzymatic activity as they relate to gene EPHA2. To generalize the intended target to other relatable targets, this assay endpoint is annotated to the kinase intended target family, where the subfamily is receptor tyrosine kinase.	enzymatic activity	percent_activity	staurosporine	loss	protein	enzyme	kinase	receptor tyrosine kinase	1	2529	ERF_CR_ENZ_hEPHA2	ERF_CR_ENZ_hEPHA2 is an assay component calculated from the ERF_CR_ENZ_hEPHA2 assay. It is designed to measure enzyme activity using a type of enzyme reporter as detected by fluorescence intensity with LANCE technology.	Changes in fluorescence intensity produced from the regulation of catalytic activity reaction involving the key substrate, ATP + Ulight-TK peptide , are indicative of changes in receptor function and kinetics related to the gene EPHA2.	single	enzyme reporter	enzyme activity	regulation of catalytic activity	Fluorescence	Fluorescence intensity	LANCE	substrate	ATP + Ulight-TK peptideÂ	protein	receptor	790	ERF_CR_ENZ_hEPHA2	ERF_CR_ENZ_hEPHA2 is a biochemical, single-readout assay that uses extracted gene-proteins in a cell-free assay. Measurements were taken 0.5 hour after chemical dosing in a 96-well plate. See EphA2 Human RTK Kinase Enzymatic LANCE Assay [Km ATP], Cerep.	0.50	9606	human	NA	cell-free	human recombinant cells	NA	NA	microplate: 96-well plate	biochemical	protein single format	single	DMSO	28	ERF	Eurofins	Eurofins is an international group of laboratories headquartered in Luxembourg, providing testing and support services to the pharmaceutical, food, environmental, agriscience and consumer products industries and to governments.	110 , EPH receptor A2, NA , EPHA2 , 1 , live , 1969 , EPHA2 , EPH receptor A2, P29317	NA, NA	NA, NA, NA, NA, NA, NA, NA, NA, NA
2577	ERF_CR_ENZ_hEPHB2	1	1	Data from the assay component ERF_CR_ENZ_hEPHB2 was analyzed at the assay endpoint, ERF_CR_ENZ_hEPHB2, in the positive analysis fitting direction relative to DMSO as the negative control and baseline of activity. Using a type of enzyme reporter, loss-of-signal activity can be used to understand changes in enzymatic activity as they relate to gene EPHB2. To generalize the intended target to other relatable targets, this assay endpoint is annotated to the kinase intended target family, where the subfamily is receptor tyrosine kinase.	enzymatic activity	percent_activity	PP2	loss	protein	enzyme	kinase	receptor tyrosine kinase	1	2530	ERF_CR_ENZ_hEPHB2	ERF_CR_ENZ_hEPHB2 is an assay component calculated from the ERF_CR_ENZ_hEPHB2 assay. It is designed to measure enzyme activity using a type of enzyme reporter as detected by fluorescence intensity with LANCE technology.	Changes in fluorescence intensity produced from the regulation of catalytic activity reaction involving the key substrate, ATP + Ulight-TK peptide, are indicative of changes in receptor function and kinetics related to the gene EPHB2.	single	enzyme reporter	enzyme activity	regulation of catalytic activity	Fluorescence	Fluorescence intensity	LANCE	substrate	ATP + Ulight-TK peptide	protein	receptor	789	ERF_CR_ENZ_hEPHB2	ERF_CR_ENZ_hEPHB2 is a biochemical, single-readout assay that uses extracted gene-proteins in a cell-free assay. Measurements were taken 0.25 hour after chemical dosing in a 96-well plate. See EphB2 Human RTK Kinase Enzymatic LANCE Assay [Km ATP], Cerep.	0.25	9606	human	NA	cell-free	human recombinant cells	NA	NA	microplate: 96-well plate	biochemical	protein single format	single	DMSO	28	ERF	Eurofins	Eurofins is an international group of laboratories headquartered in Luxembourg, providing testing and support services to the pharmaceutical, food, environmental, agriscience and consumer products industries and to governments.	115 , EPH receptor B2, NA , EPHB2 , 1 , live , 2048 , EPHB2 , EPH receptor B2, P29323	NA, NA	NA, NA, NA, NA, NA, NA, NA, NA, NA
2578	ERF_CR_ENZ_hFGFR1	1	1	Data from the assay component ERF_CR_ENZ_hFGFR1 was analyzed at the assay endpoint, ERF_CR_ENZ_hFGFR1, in the positive analysis fitting direction relative to DMSO as the negative control and baseline of activity. Using a type of enzyme reporter, loss-of-signal activity can be used to understand changes in enzymatic activity as they relate to gene FGFR1. To generalize the intended target to other relatable targets, this assay endpoint is annotated to the kinase intended target family, where the subfamily is receptor tyrosine kinase.	enzymatic activity	percent_activity	Staurosporine	loss	protein	enzyme	kinase	receptor tyrosine kinase	1	2531	ERF_CR_ENZ_hFGFR1	ERF_CR_ENZ_hFGFR1 is an assay component calculated from the ERF_CR_ENZ_hFGFR1 assay. It is designed to measure enzyme activity using a type of enzyme reporter as detected by fluorescence intensity with LANCE technology.	Changes in fluorescence intensity produced from the regulation of catalytic activity reaction involving the key substrate, ATP + Ulight-CAGAGAIETDKEYYTVKD , are indicative of changes in receptor function and kinetics related to the gene FGFR1.	single	enzyme reporter	enzyme activity	regulation of catalytic activity	Fluorescence	Fluorescence intensity	LANCE	substrate	ATP + Ulight-CAGAGAIETDKEYYTVKD	protein	receptor	770	ERF_CR_ENZ_hFGFR1	ERF_CR_ENZ_hFGFR1 is a biochemical, single-readout assay that uses extracted gene-proteins in a cell-free assay. Measurements were taken 1 hour after chemical dosing in a 96-well plate. See FGFR Human RTK Kinase Enzymatic LANCE Assay [Km ATP], Cerep.	1.00	9606	human	NA	cell-free	human recombinant insect cells	NA	NA	microplate: 96-well plate	biochemical	protein single format	single	DMSO	28	ERF	Eurofins	Eurofins is an international group of laboratories headquartered in Luxembourg, providing testing and support services to the pharmaceutical, food, environmental, agriscience and consumer products industries and to governments.	126 , fibroblast growth factor receptor 1, NA , FGFR1 , 1 , live , 2260 , FGFR1 , fibroblast growth factor receptor 1, P11362	NA, NA	NA, NA, NA, NA, NA, NA, NA, NA, NA
2579	ERF_CR_ENZ_hFGFR3	1	1	Data from the assay component ERF_CR_ENZ_hFGFR3 was analyzed at the assay endpoint, ERF_CR_ENZ_hFGFR3, in the positive analysis fitting direction relative to DMSO as the negative control and baseline of activity. Using a type of enzyme reporter, loss-of-signal activity can be used to understand changes in enzymatic activity as they relate to gene FGFR3. To generalize the intended target to other relatable targets, this assay endpoint is annotated to the kinase intended target family, where the subfamily is receptor tyrosine kinase.	enzymatic activity	percent_activity	staurosporine	loss	protein	enzyme	kinase	receptor tyrosine kinase	1	2532	ERF_CR_ENZ_hFGFR3	ERF_CR_ENZ_hFGFR3 is an assay component calculated from the ERF_CR_ENZ_hFGFR3 assay. It is designed to measure enzyme activity using a type of enzyme reporter as detected by fluorescence intensity with LANCE technology.	Changes in fluorescence intensity produced from the regulation of catalytic activity reaction involving the key substrate, ATP + Ulight-CAGAGAIETDKEYYTVKD, are indicative of changes in receptor function and kinetics related to the gene FGFR3.	single	enzyme reporter	enzyme activity	regulation of catalytic activity	Fluorescence	Fluorescence intensity	LANCE	substrate	ATP + Ulight-CAGAGAIETDKEYYTVKD	protein	receptor	775	ERF_CR_ENZ_hFGFR3	ERF_CR_ENZ_hFGFR3 is a biochemical, single-readout assay that uses extracted gene-proteins in a cell-free assay. Measurements were taken 1.5 hour after chemical dosing in a 96-well plate. See FGFR3 Human RTK Kinase Enzymatic LANCE Assay [Km ATP], Cerep.	1.50	9606	human	NA	cell-free	human recombinant cells	NA	NA	microplate: 96-well plate	biochemical	protein single format	single	DMSO	28	ERF	Eurofins	Eurofins is an international group of laboratories headquartered in Luxembourg, providing testing and support services to the pharmaceutical, food, environmental, agriscience and consumer products industries and to governments.	127 , fibroblast growth factor receptor 3, NA , FGFR3 , 1 , live , 2261 , FGFR3 , fibroblast growth factor receptor 3, P22607	NA, NA	NA, NA, NA, NA, NA, NA, NA, NA, NA

4.3 Single Chemical Search

As described in greater detail within the Data Processing sections of the tcpl vignette, a goal of multi-concentration, or MC, processing is to derive the efficacy and potency estimates for for each modeled endpoint-sample dose response. API data is available for MC levels 3 through 6, herein users can inspect the MC data including efficacy and potency estimates, model parameters, raw concentration response values, cautionary flags, and applied methods.

Loading data is completed for a given endpoint (aeid), sample (spid), chemical (dtxsid), or endpoint-sample (m4id) by specifying “fld”. To replicate the example above, query for Bisphenol A (BPA), which has DTXSID “DTXSID7020182”

## Load ToxCast data (level 5) for BPA
bpa_mc5 <- tcplLoadData(lvl = 5,          # data level
                    fld = "dtxsid",       # fields to query on
                    val = "DTXSID7020182",# values should match their corresponding 'fld'
                    type = "mc",          # default. Note: SC data is not available on APIs yet
                    add.fld = FALSE)

Set add.fld = FALSE is the option used to limit fields to those which are defaults for each level when loading from invitrodb directly. Leaving add.fld = TRUE (default) will return all available fields, i.e. all information from levels 3 through 6.

Click here to preview the first six rows of bioactivity data available for BPA.

tmpi	m5id	modl	fitc	coff	actp	model_type	chid_rep	stkc	stkc_unit	tested_conc_unit	logc	resp	pow_a	pow_p	exp2_a	exp2_b	exp3_a	exp3_b	exp3_p	exp5_p	gnls_p	gnls_q	hill_p	pow_er	cnst_er	exp2_er	exp3_er	exp4_er	exp4_ga	exp4_tp	exp5_er	exp5_ga	exp5_tp	gnls_er	gnls_ga	gnls_la	gnls_tp	hill_er	hill_ga	hill_tp	poly1_a	poly2_a	poly2_b	pow_aic	pow_cov	pow_rme	pow_top	cnst_aic	cnst_rme	exp2_aic	exp2_cov	exp2_rme	exp2_top	exp3_aic	exp3_cov	exp3_rme	exp3_top	exp4_aic	exp4_cov	exp4_rme	exp4_top	exp5_aic	exp5_cov	exp5_rme	exp5_top	gnls_aic	gnls_cov	gnls_rme	gnls_top	hill_aic	hill_cov	hill_rme	hill_top	poly1_er	poly2_er	pow_a_sd	pow_ac50	pow_p_sd	all_onesd	exp2_a_sd	exp2_ac50	exp2_b_sd	exp3_a_sd	exp3_ac50	exp3_b_sd	exp3_p_sd	exp4_ac50	exp5_ac50	exp5_p_sd	gnls_ac50	gnls_p_sd	gnls_q_sd	hill_ac50	hill_p_sd	poly1_aic	poly1_cov	poly1_rme	poly1_top	poly2_aic	poly2_cov	poly2_rme	poly2_top	pow_er_sd	exp2_er_sd	exp3_er_sd	exp4_er_sd	exp4_ga_sd	exp4_tp_sd	exp5_er_sd	exp5_ga_sd	exp5_tp_sd	gnls_er_sd	gnls_ga_sd	gnls_la_sd	gnls_tp_sd	hill_er_sd	hill_ga_sd	hill_tp_sd	poly1_a_sd	poly1_ac50	poly2_a_sd	poly2_ac50	poly2_b_sd	poly1_er_sd	poly2_er_sd	pow_success	cnst_success	exp2_success	exp3_success	exp4_success	exp5_success	gnls_success	hill_success	poly1_success	poly2_success	gnls_ac50_loss	p	er	ga	tp	ac5	bmr	mll	top	ac10	ac20	ac50	rmse	caikwt	top_over_cutoff	a	bmd	bmdl	bmdu	ac1sd	q	la	ac50_loss	acc	b	flag	mc6Mthd_id	aeid	m4id	spid	chid	casn	chnm	dtxsid	bmad	resp_max	resp_min	max_mean	max_mean_conc	max_med	max_med_conc	logc_max	logc_min	nconc	npts	nrep	dsstox_substance_id	conc
716	4787296	exp5	13	0.0791812	NA	2	0	20.0	mM	uM	1.00000, 0.00000, 1.60206, 0.60206	-0.020, 0.008, -0.049, 0.001	-0.0014428	0.9592987	-4.6448208	3753.223844	-0.0353311	47.31448	0.7860427	7.9999999	7.9999999	2.497212	7.9999995	-5.068015	-3.866838	-5.064046	-4.986425	-5.061595	17.730331	-0.0588000	-6.079040	10.354609	-0.0490002	-6.077958	10.47740	686.7938	-0.0490416	-6.077936	10.47567	-0.0490014	-0.0012439	-6.8404953	5.537761e+03	-21.98427	1	0.0066778	-0.0496647	-15.56073	0.0267675	-21.96011	1	0.0066940	-0.0497669	-19.53428	1	0.0070553	-0.0495371	-21.67067	1	0.0071217	-0.0588000	-25.55154	1	0.0040322	-0.0490002	-21.54910	1	0.0040325	-0.0490120	-25.54909	1	0.0040325	-0.0490014	-5.065595	-5.062728	0.0015788	19.420385	0.2994375	0.1560347	49.9228699	20.05329	4.012005e+04	0.0897782	21.159764	98.94007	0.4298393	17.730331	10.354609	12.4430868	10.47590	NA	NA	10.47567	6.7570679	-23.96775	1	0.0066876	-0.0497550	-21.95744	1	0.0066963	-0.0497667	0.4173604	0.4176039	0.4298381	0.4808176	9.506270	0.0173181	0.6586148	0.5777096	0.0020450	NA	NA	NA	NA	0.6590755	0.4313022	0.0020411	0.0001400	20	64.8364066	20.07171	5.210984e+04	0.4173350	0.4178536	1	1	1	1	1	1	1	1	1	1	687.126	7.9999999	-6.079040	10.35461	-0.0490002	7.478046	0.2104908	16.77577	-0.0490002	8.182109	8.986769	10.354609	0.0040322	0.0067235	0.6188365	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Average number of replicates per conc is less than 2, Number of concentrations tested is less than 4	13, 14	146	392721	TP0000077C05	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	0.0080000	-0.0490000	0.0080000	0.00000	0.0080000	0.00000	1.60206	0.00000	4	4	1	DTXSID7020182	10, 1, 40, 4
1405	4787985	poly1	13	0.0791812	NA	2	0	20.3	mM	uM	1.60206, 0.30103, 1.00000, 1.60206, 0.69897, 0.30103, 1.00000, 0.69897	-0.0162930040, 0.0009765513, -0.0040055670, -0.0527708230, -0.0084209870, -0.0188779660, -0.0175304400, -0.0142500770	-0.0047526	0.4718645	-6.7732303	6434.987816	-0.0169112	41.98541	0.3580042	0.5638685	0.5897359	6.569511	0.5895251	-4.643124	-4.096128	-4.567034	-4.638488	-4.594978	11.623193	-0.0329091	-4.664331	24.088362	-0.0414382	-4.658047	80.63318	3973.4440	-0.0633250	-4.658091	80.70038	-0.0633250	-0.0010560	-9.3991818	8.932530e+03	-42.06359	1	0.0118185	-0.0270949	-36.63585	0.0223743	-40.94052	1	0.0125351	-0.0422336	-40.12324	1	0.0116245	-0.0282745	-41.59935	1	0.0118204	-0.0329091	-39.96494	1	0.0122098	-0.0414382	-35.96631	0	0.0121691	-0.0544430	-39.96631	1	0.0121700	-0.0633250	-4.566625	-4.566803	0.0049698	9.206645	0.4209828	0.1560347	98.3423031	20.03108	9.320505e+04	NA	10.438421	NA	NA	11.623193	24.088362	0.5653226	49.95301	NA	NA	80.70038	0.6376805	-42.94527	1	0.0125330	-0.0422383	-40.93844	1	0.0125421	-0.0422782	0.3612291	0.3462718	NA	0.3513932	21.949710	0.0413074	0.3646821	110.6663101	0.0761294	NA	NA	NA	NA	0.3650052	550.6860491	0.1509537	0.0003566	20	114.4215999	20.04458	1.082021e+05	0.3462516	0.3464412	1	1	1	1	1	1	1	1	1	1	4040.330	NA	-4.566625	NA	NA	2.000000	0.2104908	23.47263	-0.0422383	4.000000	8.000000	20.000000	0.0125330	0.0409060	0.5334376	-0.0010560	199.3367	141.6199	474.6410	147.7662	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4 , Bmd > ac50, indication of high baseline variability	14, 9	146	393410	TP0000496A08	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	0.0009766	-0.0527708	-0.0089507	0.30103	-0.0089507	0.30103	1.60206	0.30103	4	8	2	DTXSID7020182	40, 2, 10, 40, 5, 2, 10, 5
1423	4788003	pow	13	0.0791812	NA	2	1	20.3	mM	uM	1.60206, 0.30103, 1.00000, 0.69897, 0.30103, 1.00000, 0.69897, 1.60206	-0.058351750, -0.022358924, -0.025285470, -0.022031331, -0.018866405, -0.035500716, -0.006874923, -0.021082722	-0.0139307	0.3000000	-12.3832514	9679.864437	-0.0434129	105.87011	0.3000011	0.3641961	0.3831522	7.890175	0.3831893	-4.648191	-3.627362	-4.108325	-4.615223	-4.659977	1.529477	-0.0279641	-4.653095	5.845479	-0.0476607	-4.651029	32.87705	3754.6495	-0.0700221	-4.651011	32.87115	-0.0700221	-0.0012817	-18.0726077	1.414194e+04	-42.21215	1	0.0114495	-0.0421299	-30.51788	0.0298697	-34.46179	1	0.0178031	-0.0512770	-40.02269	1	0.0121238	-0.0481957	-41.11048	1	0.0132999	-0.0279641	-40.14713	1	0.0115997	-0.0476607	-36.15238	0	0.0115622	-0.0576111	-40.15238	1	0.0115621	-0.0700221	-4.109078	-4.108627	0.0069597	3.968503	0.2533258	0.1560347	143.2676220	20.02066	1.116325e+05	0.1000142	6.939221	538.72442	0.1906033	1.529477	5.845479	0.4361952	12.90624	NA	NA	32.87115	0.5388169	-36.46933	1	0.0177949	-0.0512669	-34.45904	1	0.0178048	-0.0512623	0.3323388	0.3046685	0.3661416	0.4087137	2.387444	0.0096831	0.3447170	38.8186464	0.0786779	NA	NA	NA	NA	0.3418461	382.4619541	0.1713404	0.0003754	20	179.3710746	20.02820	1.398150e+05	0.3045941	0.3045916	1	1	1	1	1	1	1	1	1	1	3796.678	0.3000000	-4.648191	NA	NA	NA	0.2104908	24.10608	-0.0421299	NA	NA	3.968503	0.0114495	0.0028798	0.5320695	-0.0139307	NA	NA	NA	NA	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4	14	146	393428	TP0000498A08	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	-0.0068749	-0.0583518	-0.0144531	0.69897	-0.0144531	0.69897	1.60206	0.30103	4	8	2	DTXSID7020182	40, 2, 10, 5, 2, 10, 5, 40
1434	4788014	pow	13	0.0791812	NA	2	0	20.3	mM	uM	1.00000, 0.69897, 0.69897, 1.60206, 0.30103, 1.00000, 1.60206, 0.30103	-0.042423830, -0.018199127, -0.039300120, -0.070243575, -0.034689017, -0.026189076, -0.042190440, -0.004385219	-0.0159883	0.3399982	-17.0130357	10522.355008	-0.0392648	52.20333	0.3000006	0.5499441	0.6323059	5.781948	0.6345849	-4.418804	-3.324452	-3.988125	-4.372431	-4.402534	5.466988	-0.0541936	-4.416659	8.256625	-0.0674604	-4.416469	15.48482	1175.5642	-0.0842923	-4.417604	15.44867	-0.0842923	-0.0016196	-23.9969775	1.486670e+04	-39.90897	1	0.0123060	-0.0560401	-25.88774	0.0392080	-32.28963	1	0.0206072	-0.0647970	-37.67170	1	0.0125742	-0.0595805	-39.22067	1	0.0131935	-0.0541936	-37.84524	1	0.0123777	-0.0674604	-33.83603	1	0.0123897	-0.0753860	-37.83597	1	0.0123894	-0.0842923	-3.989664	-3.989254	0.0073330	5.208024	0.1590385	0.1560347	190.3152226	20.01901	1.174087e+05	0.0735880	7.764359	205.40892	0.1915197	5.466988	8.256625	0.4903405	11.07184	0.6959329	20835.5099	15.44867	0.7135147	-34.29770	1	0.0205975	-0.0647854	-32.28631	1	0.0206107	-0.0647394	0.2844967	0.3081117	0.2965407	0.2975840	3.362452	0.0138993	0.2856747	20.4895366	0.0585480	0.2858832	61.01501	14317870	0.0991375	0.2856987	62.2552443	0.1016970	0.0003563	20	226.2142000	20.02683	1.397848e+05	0.3079642	0.3079437	1	1	1	1	1	1	1	1	1	1	1195.421	0.3399982	-4.418804	NA	NA	NA	0.2104908	22.95449	-0.0560401	NA	NA	5.208024	0.0123060	0.0009014	0.7077452	-0.0159883	NA	NA	NA	NA	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4	14	146	393439	TP0000499A10	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0227491	-0.0043852	-0.0702436	-0.0195371	0.30103	-0.0195371	0.30103	1.60206	0.30103	4	8	2	DTXSID7020182	10, 5, 5, 40, 2, 10, 40, 2
716	4789331	poly1	13	0.0791812	NA	2	0	20.0	mM	uM	0.60206, 1.60206, 0.00000, 1.00000	-0.004, -0.026, 0.019, -0.001	-0.0000210	1.9298414	-0.0016851	14.292354	-0.0150948	39.97355	1.5616831	2.5720118	3.4353461	4.245239	3.4375239	-5.105207	-4.269141	-5.119732	-5.111167	-4.784525	23.483014	-0.0312000	-5.098243	27.687923	-0.0312000	-5.094068	25.08753	1084.0390	-0.0312000	-5.094090	25.09852	-0.0312000	-0.0006208	-0.0001298	2.930628e+00	-20.32558	1	0.0096963	-0.0259813	-19.19290	0.0162327	-20.34607	1	0.0097224	-0.0259890	-18.33919	1	0.0096996	-0.0259795	-18.87484	1	0.0107752	-0.0312000	-18.30678	1	0.0096990	-0.0312000	-14.29357	1	0.0097036	-0.0311514	-18.29357	1	0.0097036	-0.0312000	-4.957939	-5.109174	0.0002462	27.930138	3.1772449	0.1748452	0.0095168	30.93808	2.714077e+01	0.6055772	29.459402	649.28415	8.3282625	23.483014	27.687923	6.2508295	25.06480	17.4516974	5629.6852	25.09852	16.5873187	-21.67413	1	0.0101951	-0.0248308	-20.32728	1	0.0097082	-0.0259481	0.5904399	0.6019969	0.6169114	0.5241570	26.510136	0.0238649	0.5875827	83.9234059	0.1094183	0.5865875	122.93077	4740412	0.1292349	0.5863450	116.3790611	0.1223919	0.0001549	20	0.0013238	27.87339	1.549231e+01	0.5361260	0.5925829	1	1	1	1	1	1	1	1	1	1	1084.834	NA	-4.957939	NA	NA	2.000000	0.2358661	12.83706	-0.0248308	4.000000	8.000000	20.000000	0.0101951	0.2243287	0.3135943	-0.0006208	379.9576	263.9718	750.4563	281.6587	NA	NA	NA	NA	NA	Average number of replicates per conc is less than 2, Bmd > ac50, indication of high baseline variability , Number of concentrations tested is less than 4	13, 9, 14	148	394756	TP0000077C05	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0257590	0.0190000	-0.0260000	0.0190000	0.00000	0.0190000	0.00000	1.60206	0.00000	4	4	1	DTXSID7020182	4, 40, 1, 10
1405	4790020	poly1	13	0.0791812	NA	2	0	20.3	mM	uM	1.60206, 0.30103, 1.60206, 0.69897, 0.30103, 1.00000, 1.00000, 0.69897	-0.0195828230, -0.0065298300, -0.0368289760, -0.0094431750, -0.0198203400, 0.0202787030, -0.0003974539, 0.0159239450	0.0000000	7.4669657	-0.0000014	4.023976	-0.0190818	40.49855	7.8399712	7.9999918	7.9468189	1.503535	7.9520649	-4.441523	-4.078191	-4.441933	-4.441199	-4.322145	28.545146	-0.0338471	-4.441346	34.189416	-0.0309185	-4.441518	36.07627	3466.8814	-0.0406638	-4.441393	37.24481	-0.0441948	-0.0006259	-0.0000004	1.430626e-01	-39.66564	1	0.0129343	-0.0282016	-37.65645	0.0191359	-39.66287	1	0.0129370	-0.0281575	-37.66576	1	0.0129342	-0.0282031	-37.41739	1	0.0151599	-0.0338471	-37.66559	1	0.0129343	-0.0309185	-33.66552	1	0.0129344	-0.0404684	-37.66557	1	0.0129344	-0.0441948	-4.365286	-4.479115	0.0000004	36.453992	0.0861014	0.1748452	0.0000016	37.21099	1.307239e-01	NA	37.553893	NA	NA	28.545146	34.189416	82.7038416	36.04208	75.8717424	271.3305	37.24481	NA	-40.13079	1	0.0145042	-0.0250370	-39.24680	1	0.0133075	-0.0275892	0.3020025	0.3019179	NA	0.3184006	34.869636	0.0304292	0.3019906	359.2796286	0.6586123	0.3019695	272.42214	2782192	0.8085816	NA	NA	NA	0.0002342	20	0.0000011	28.26337	2.302960e-02	0.3106562	0.2973885	1	1	1	1	1	1	1	1	1	1	3489.111	NA	-4.365286	NA	NA	2.000000	0.2358661	22.06539	-0.0250370	4.000000	8.000000	20.000000	0.0145042	0.2249296	0.3161988	-0.0006259	376.8280	232.5859	1104.4237	279.3387	NA	NA	NA	NA	NA	Number of concentrations tested is less than 4 , Bmd > ac50, indication of high baseline variability	14, 9	148	395445	TP0000496A08	20182	80-05-7	Bisphenol A	DTXSID7020182	0.0257590	0.0202787	-0.0368290	0.0099406	1.00000	0.0099406	1.00000	1.60206	0.30103	4	8	2	DTXSID7020182	40, 2, 40, 5, 2, 10, 10, 5

4.4 Plotting

tcplPlot is tcpl’s single flexible plotting function, allowing for interactive yet consistent visualization of concentration-response curves via customizable parameters. The standalone plotting utility is built with the R libraries plotly and ggplot2 to display the additional curve-fitting models. The tcplPlot function requires the selection of a type (type), field (fld), and value (val) to load the necessary data and display the associated plots.

While supplying multiple identifiers (through val) is valid, supplying multiple fields is not. For example, if fld = “spid”, no aeid can be specified, meaning every matching spid will be plotted. If fld = “aeid”, every sample within the given endpoint(s) will be plotted. If fld = “m4id”, only one plot will output for every each m4id input. Combinations of fields are currently not supported with tcplPlot using API connections. Therefore, if looking for a specific aeid and spid combo, one should determine the corresponding m4id to plot, like so:

Example plot for a single m4id, i.e. endpoint-sample of BPA tested in the OT_ER_ERaERa_1440, is displayed

## Plot endpoint-sample (M4ID)
tcplPlot(val = 1222891, output = "console", verbose = TRUE, flags = TRUE)

4.5 Learning Check Point: tcpl and API Objectives

Users should be able to:

Load required R packages for use with tcpl and/or ctxR
Query API with tcpl for Assay Annotations and Data
Explore plotting functionality from tcpl

5 Additional API Examples

The following guided examples provide users the opportunity to interact with CTX API data using tcpl and ctxR. The following solutions are provided for demonstrative purposes, and additional alternate solutions are possible.

5.1 Batch Chemical Search by Chemical List

Chemical lists are curated and made publicly available by the US EPA in the Distributed Structure-Searchable Toxicity (DSSTox) database. ctxR functions can be used to query the CTX Chemical API and retrieve the chemical lists associated with a particular chemical. In this example, query for chemical lists containing for Bisphenol A (BPA), which has DTXSID “DTXSID7020182”

BPA_lists <- get_lists_containing_chemical(DTXSID = 'DTXSID7020182')

Click here to reveal the first six chemical lists containing BPA.


BIOSOLIDS	Navigation Panel to Biosolid Lists	federal	PUBLIC	Biosolids lists change over time and are versioned iteratively. This panel navigates between the various versions.	Biosolids lists change over time and are versioned iteratively. This panel navigates between the various versions which will be released over time. The list of substances displayed below represents the latest iteration of biosolids (BIOSOLOIDS2021 - November 2021). For the versioned lists please use the hyperlinked lists below.<br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/BIOSOLIDS2021’ target=’_blank’>BIOSOLIDS2021 - November 2021</a><br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/BIOSOLIDS2022’ target=’_blank’>BIOSOLIDS2022 - December 2022</a><br/><br/>	\|726 \|2021-12-19T11:00:24.	00+00:00 \|2023-09-26T13:28:20.
BIOSOLIDS2021	LIST: Chemicals in biosolids (2021)	federal	PUBLIC	Chemicals detected in biosolids (nutrient-rich organic materials produced from wastewater treatment facilities) (Last Updated November 9th 2021)	Biosolids are a product of the wastewater treatment process. During wastewater treatment the liquids are separated from the solids. Those solids are then treated physically and chemically to produce a semisolid, nutrient-rich product known as biosolids. The terms ‘biosolids’ and ‘sewage sludge’ are often used interchangeably. <a href=‘https://www.epa.gov/sites/default/files/2017-08/documents/federal-water-pollution-control-act-508full.pdf’ target=’_blank’>Section 405(d) of the Clean Water Act (CWA)</a>  requires the United States Environmental Protection Agency (EPA) to (1) develop a regulation to establish pollutant limits and management practices to protect human health and the environment from any reasonably anticipated adverse effects of pollutants that might be present in sewage sludge; and (2) review sewage sludge regulations every two years to identify any additional pollutants that may occur in biosolids and to set regulations for pollutants identified in biosolids if sufficient scientific evidence shows they may harm human health or the environment. The regulation <a href=‘https://www.epa.gov/biosolids/biosolids-laws-and-regulations#standards’ target=’_blank’>40 CFR Part 503, Standards for the Use or Disposal of Sewage Sludge</a> , was published on February 19, 1993 (58 FR 9248). Part 503 established pollutants limits for ten metals. Since 1993, EPA has conducted eight <a href=‘https://www.epa.gov/biosolids/biennial-reviews-sewage-sludge-standards’ target=’_blank’>biennial reviews</a> and three <a href=‘https://www.epa.gov/biosolids/sewage-sludge-surveys’ target=’_blank’>national sewage sludge surveys</a> to review additional pollutants found in biosolids and assess possible exposure from those chemicals. To date, 726 chemicals have been found in biosolids. You can learn more about the curation of the list of chemical pollutants here: <a href=‘https://www.nature.com/articles/s41597-022-01267-9’ target=’_blank’>https://www.nature.com/articles/s41597-022-01267-9</a>;. Concentration data is also available for 484 chemical pollutants detected in the three national sewage sludge surveys here: <a href=‘https://www.nature.com/articles/s41597-022-01267-9#Sec11’ target=’_blank’>Supplementary Information Table 4 (https://www.nature.com/articles/s41597-022-01267-9#Sec11)</a>;. To view all the microbial pollutants found in biosolids see Table B-1, Chemical and Microbial Pollutants Identified in Biosolids in <a href=‘https://www.epa.gov/biosolids/biennial-report-no-8-reporting-period-2018-2019’ target=’_blank’>Biennial Review No. 8</a>. (Last Updated November 9th 2021)	\|726 \|2021-11-09T16:57:37.00	+00:00 \|2022-10-05T22:30:53.00
BIOSOLIDS2022	LIST: Chemicals in biosolids (2022)	federal	PUBLIC	Chemicals detected in biosolids (nutrient-rich organic materials produced from wastewater treatment facilities) (Last Updated December 21st 2022)	Biosolids are a product of the wastewater treatment process. During wastewater treatment the liquids are separated from the solids. Those solids are then treated physically and chemically to produce a semisolid, nutrient-rich product known as biosolids. The terms ‘biosolids’ and ‘sewage sludge’ are often used interchangeably though biosolids typically means treated sewage sludge that meet federal and state requirements and are applied to land as a soil amendment. <a href=‘https://www.epa.gov/sites/default/files/2017-08/documents/federal-water-pollution-control-act-508full.pdf’ target=’_blank’>Section 405(d) of the Clean Water Act (CWA)</a>  requires the United States Environmental Protection Agency (EPA) to (1) develop a regulation to establish pollutant limits and management practices to protect human health and the environment from any reasonably anticipated adverse effects of pollutants that might be present in sewage sludge; and (2) review sewage sludge regulations every two years to identify any additional pollutants that may occur in biosolids and to set regulations for pollutants identified in biosolids if sufficient scientific evidence shows they may harm human health or the environment. The regulation <a href=‘https://www.epa.gov/biosolids/biosolids-laws-and-regulations#standards’ target=’_blank’>40 CFR Part 503, Standards for the Use or Disposal of Sewage Sludge</a> , was published on February 19, 1993 (58 FR 9248). Part 503 established pollutants limits for ten metals. Since 1993, EPA has conducted nine <a href=‘https://www.epa.gov/biosolids/biennial-reviews-sewage-sludge-standards’ target=’_blank’>biennial reviews</a> and three <a href=‘https://www.epa.gov/biosolids/sewage-sludge-surveys’ target=’_blank’>national sewage sludge surveys</a> to identify additional pollutants found in biosolids. To date, 739 chemicals have been found in biosolids. You can learn more about the curation of the list of chemical pollutants through 2021 here: <a href=‘https://www.nature.com/articles/s41597-022-01267-9’ target=’_blank’>https://www.nature.com/articles/s41597-022-01267-9</a>;. Concentration data is also available for 484 chemical pollutants detected in the three national sewage sludge surveys here: <a href=‘https://www.nature.com/articles/s41597-022-01267-9#Sec11’ target=’_blank’>Supplementary Information Table 4 (https://www.nature.com/articles/s41597-022-01267-9#Sec11)</a>;. To view all the microbial pollutants found in biosolids see Appendix B, ‘Table B-3: Microbial Pollutants Identified in Biosolids’ in <a href=‘https://www.epa.gov/biosolids/biennial-reviews-sewage-sludge-standards’ target=’_blank’>Biennial Report No.9 (Reporting Period 2020-2021)</a>. (Last Updated December 21st,	\|739 \|2022-10-05T22:32:34.00	+00:00 \|2022-12-23T00:41:26.00
CCL	WATER\|EPA: Chemical Contaminants - Navigation Panel to Chemical Candidate Lists	federal	PUBLIC	Chemical Candidate Lists are versioned iteratively and this panel navigates between the various versions.	The Safe Drinking Water Act (SDWA), as amended in 1996, requires the United States Environmental Protection Agency (EPA) to publish every five years a list of drinking water contaminants, known as the Contaminant Candidate List (CCL), that at the time of publication:<br/> • are not subject to any proposed or promulgated National Primary Drinking Water Regulation,<br/> • are known or anticipated to occur in public water systems (PWSs), and <br/> • may require regulation under the SDWA. <br/><br/> The CCLs provided in the CompTox dashboard are versioned iteratively and this description navigates between the various versions of the lists. The list of substances displayed below represents the latest iteration of the list (CCL 5 - November 2022) and only display the chemical contaminants. The CCL 5 PFAS list is listed separately. For the versioned lists please use the hyperlinked lists below.<br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL5’ target=’_blank’>CCL5 - November 2022</a> This list <br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL4’ target=’_blank’>CCL4 - November 2016</a> <br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL3’ target=’_blank’>CCL3 - October 2009</a> <br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL2’ target=’_blank’>CCL2 - February 2005</a><br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL1’ target=’_blank’>CCL1 - March 1998</a><br/><br/>	\|93 \|2022-	0-21T18:35:26.000+00:00 \|2022-
CCL5	WATER\|EPA: Chemical Contaminants - CCL 5	federal	PUBLIC	The Contaminant Candidate List (CCL) is a list of contaminants that are known or anticipated to occur in public water systems. Version 5 is known as CCL 5.	The Contaminant Candidate List (CCL) is a list of contaminants that, at the time of publication, are not subject to any proposed or promulgated national primary drinking water regulations, but are known or anticipated to occur in public water systems. Contaminants listed on the CCL may require future regulation under the Safe Drinking Water Act (SDWA). EPA announced the <a href=‘https://www.epa.gov/ccl/contaminant-candidate-list-5-ccl-5’ target=’_blank’>fifth Drinking Water Contaminant Candidate List (CCL 5)</a> on November 2nd 2022. The CCL 5 includes 66 individually listed chemicals, 3 chemical groups (cyanotoxins, disinfection byproducts (DBPs), per- and polyfluoroalkyl substances (PFAS)), and 12 microbial contaminants (not displayed in the CompTox List below). The group of cyanotoxins include, but is not limited to: anatoxin-a, cylindrospermopsin, microcystins, and saxitoxin. The DBP group includes 23 unregulated DBPs that were either publicly nominated and/or among the top chemicals in the CCL 5 Universe. For the purposes of CCL 5, the PFAS group includes chemicals that contain at least one of these three structures: <br/><br/> • R-(CF2)-CF(R′)R′′, where both the CF2 and CF moieties are saturated carbons, and none of the R groups can be hydrogen <br/> • R-CF2OCF2-R′, where both the CF2 moieties are saturated carbons, and none of the R groups can be hydrogen<br/> • CF3C(CF3)RR′, where all the carbons are saturated, and none of the R groups can be hydrogen<br/><br/> The CompTox dashboard also includes a separate list of PFAS (<a href=‘https://comptox.epa.gov/dashboard/chemical-lists/CCL5PFAS’ target=’_blank’>WATER\|EPA: Chemical Contaminants - CCL 5 PFAS subset</a>) that meet the CCL 5 structural definition. <br/><br/> The CCL Chemical Candidate Lists are versioned iteratively and this description navigates between the various versions of the lists. The list of substances displayed below represents only the chemical CCL 4 contaminants. For the versioned lists, please use the hyperlinked lists below.<br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL5’ target=’_blank’>CCL5 - November 2022</a> This list <br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL4’ target=’_blank’>CCL4 - November 2016</a> <br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL3’ target=’_blank’>CCL3 - October 2009</a> <br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL2’ target=’_blank’>CCL2 - February 2005</a><br/><br/> <a href=‘https://comptox.epa.gov/dashboard/chemical_lists/CCL1’ target=’_blank’>CCL1 - March 1998</a><br/><br/>	\|93 \|2	22-10-26T21:40:56.000+00:00 \|2
CDR2016	CDR: Chemical Data Reporting 2016	federal	PUBLIC	Chemical Data Reporting (CDR) 2016 Use data.	The <a href=‘https://www.epa.gov/chemical-data-reporting/basic-information-about-chemical-data-reporting#what’ target=’_blank’>Chemical Data Reporting (CDR) rule</a> under the Toxic Substances Control Act (TSCA), requires manufacturers (including importers) to provide EPA with information on the production and use of chemicals in commerce. <br/> Under the CDR rule, EPA collects basic exposure-related information including information on the types, quantities and uses of chemical substances produced domestically and imported into the United States. The CDR database constitutes the most comprehensive source of basic screening-level, exposure-related information on chemicals available to EPA, and is used by the Agency to protect the public from potential chemical risks. <br/> The information is collected every four years from manufacturers (including importers) of certain chemicals in commerce generally when production volumes for the chemical are 25,000 lbs or greater for a specific reporting year. Collecting the information every four years assures that EPA and (for non-confidential data) the public have access to up-to-date information on chemicals. <br/> The CDR rule is required by section 8(a) of the Toxic Substances Control Act (TSCA) and was formerly known as the Inventory Update Rule (IUR). <br/>	\|8035 \|2021-10-18T21:59:4	.000+00:00 \|2021-10-18T22:25:4

BPA is included on the Contaminant Candidate Lists (CCLs). CCLs are lists of contaminants that, at the time of publication, are not subject to any proposed or promulgated national primary drinking water regulations, but are known or anticipated to occur in public water systems. Contaminants listed on the CCL may require future regulation under the Safe Drinking Water Act (SDWA). EPA announced the first Drinking Water Contaminant Candidate List (CCL1) on March 2, 1998 with the most recent update (CCL5) released on November 2nd, 2022. The CCL Chemical Candidate Lists are versioned iteratively and the past versions of the lists available on via CTX APIs. The CCL5 list also contains PFAS compounds that meet 3 structural definitions, available under the ‘CCL5PFAS’ list acronym. The purposes of this example, only the main ‘CCL5’ list will be considered.

Leveraging the CTX APIs, ToxCast bioactivity data will be compared between versions of the water contaminant priority lists. Using the CCD chemical list acronyms and ctxR functions for the CTX Chemical API, chemicals associated with each list will be retrieved.

## Retrieve chemicals in lists
ccl1 <- get_chemicals_in_list('ccl1')
ccl5 <- get_chemicals_in_list('ccl5')

## Get chemical counts per list
length(ccl1$dtxsid)

## [1] 50

length(ccl5$dtxsid)

## [1] 93

id	cpdataCount	inchikey	wikipediaArticle	monoisotopicMass	percentAssays	pubchemCount	pubmedCount	sourcesCount	qcLevel	qcLevelDesc	totalAssays	pubchemCid	relatedSubstanceCount	relatedStructureCount	casrn	compoundId	genericSubstanceId	preferredName	activeAssays	molFormula	hasStructureImage	iupacName	smiles	inchiString	qcNotes	qsarReadySmiles	msReadySmiles	irisLink	pprtvLink	descriptorStringTsv	isMarkush	dtxsid	dtxcid	toxcastSelect
552395	51	XMTQQYYKAHVGBJ-UHFFFAOYSA-N	DCMU	232.01702	12	165	1257	146	1	Level 1: Expert curated, highest confidence in accuracy and consistency of unique chemical identifiers	701	3120	13	9	330-54-1	446	20446	Diuron	86	C9H10Cl2N2O	1	N’-(3,4-Dichlorophenyl)-N,N-dimethylurea	CN(C)C(=O)NC1=CC(Cl)=C(Cl)C=C1	InChI=1S/C9H10Cl2N2O/c1-13(2)9(14)12-6-3-4-7(10)8(11)5-6/h3-5H,1-2H3,(H,12,14)	NA	CN(C)C(=O)NC1=CC(Cl)=C(Cl)C=C1	CN(C)C(=O)NC1=CC(Cl)=C(Cl)C=C1	233	NA	0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0	0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0 0
1677289	24	UFBJCMHMOXMLKC-UHFFFAOYSA-N	2,4-Dinitrophenol	184.01202	23	183	1694	132	1	Level 1: Expert curated, highest confidence in accuracy and consistency of unique chemical identifiers	572	1493	1	1	51-28-5	523	20523	2,4-Dinitrophenol	129	C6H4N2O5	1	2,4-Dinitrophenol	OC1=C(C=C(C=C1)N+=O)[N+	([O-])=O\|InChI=1S/C6H4N2O5/c9-6-2-1-4(7(10)11)3-5(6)8(12)13/h1-3,9H	\|NA	\|OC1=C(C=C(C=C1)N+=O)N+=O\|OC1=C(C=C(C=C	)N+=O)N+=O\|	52 \|Dinitrophenol24 \|0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0	0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0 0
1041244	38	RMBFBMJGBANMMK-UHFFFAOYSA-N	2,4-Dinitrotoluene	182.03276	3	134	379	119	1	Level 1: Expert curated, highest confidence in accuracy and consistency of unique chemical identifiers	601	8461	11	11	121-14-2	529	20529	2,4-Dinitrotoluene	21	C7H6N2O4	1	1-Methyl-2,4-dinitrobenzene	CC1=C(C=C(C=C1)N+=O)[N+	([O-])=O\|InChI=1S/C7H6N2O4/c1-5-2-3-6(8(10)11)4-7(5)9(12)13/h2-4H,1H3	\|NA	\|CC1=C(C=C(C=C1)N+=O)N+=O\|CC1=C(C=C(C=C	)N+=O)N+=O\|	24 \|NA \|0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0	0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0 0
1287806	23	DOFZAZXDOSGAJZ-UHFFFAOYSA-N	Disulfoton	274.02848	7	106	102	111	1	Level 1: Expert curated, highest confidence in accuracy and consistency of unique chemical identifiers	731	3118	4	4	298-04-4	2018	22018	Disulfoton	51	C8H19O2PS3	1	O,O-Diethyl S-[2-(ethylsulfanyl)ethyl] phosphorodithioate	CCOP(=S)(OCC)SCCSCC	InChI=1S/C8H19O2PS3/c1-4-9-11(12,10-5-2)14-8-7-13-6-3/h4-8H2,1-3H3	NA	CCOP(=S)(OCC)SCCSCC	CCOP(=S)(OCC)SCCSCC	154	Disulfoton	0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0	0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0 0
577791	37	SCYULBFZEHDVBN-UHFFFAOYSA-N	1,1-Dichloroethane	97.96901	0	219	23	101	1	Level 1: Expert curated, highest confidence in accuracy and consistency of unique chemical identifiers	234	6365	NA	NA	75-34-3	437	20437	1,1-Dichloroethane	1	C2H4Cl2	1	1,1-Dichloroethane	CC(Cl)Cl	InChI=1S/C2H4Cl2/c1-2(3)4/h2H,1H3	NA	CC(Cl)Cl	CC(Cl)Cl	409	Dichloroethane11	0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0	0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0 0
44001	19	HFZWRUODUSTPEG-UHFFFAOYSA-N	2,4-Dichlorophenol	161.96392	3	163	429	132	1	Level 1: Expert curated, highest confidence in accuracy and consistency of unique chemical identifiers	595	8449	4	4	120-83-2	439	20439	2,4-Dichlorophenol	19	C6H4Cl2O	1	2,4-Dichlorophenol	OC1=C(Cl)C=C(Cl)C=C1	InChI=1S/C6H4Cl2O/c7-4-1-2-6(9)5(8)3-4/h1-3,9H	2,4-DCP Metabolite of 2,4-	\|OC1=C(Cl)C=C(Cl)C=C1	\|OC1=C(Cl)C=C(Cl)C=C1	\|41	\|Dichlorophenol2	\|0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0	0 0 0 0 0	0 0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0 0

Not shown, but the format between lists will be identical.

The CCL1 list includes 50 chemicals whereas CCL5 list includes 93 chemicals. With the two chemical lists available, consider ToxCast bioactivity assay coverage. NOTE: Given the amount of data being returned, this may take awhile to run and some DTXSIDs may not return any ToxCast data.

## Load ToxCast data for each chemical list
ccl1_mc5 <- tcplLoadData(lvl = 5, fld = "dtxsid",val = ccl1$dtxsid, type = "mc", add.fld = TRUE) 
ccl5_mc5 <- tcplLoadData(lvl = 5, fld = "dtxsid",val = ccl5$dtxsid, type = "mc", add.fld = TRUE)

With Level 5 data loaded for the two chemical lists, summary statistics and potency distributions between chemical lists can be examined.

Click here to reveal summary statistics and potency distributions between chemical lists.

## Compute summary statistics
length(unique(ccl1_mc5$dtxsid))

## [1] 38

length(unique(ccl1_mc5$aeid))

## [1] 1067

length(unique(ccl5_mc5$dtxsid))

## [1] 69

length(unique(ccl5_mc5$aeid))

## [1] 1200

median(ccl1_mc5$ac50, na.rm=TRUE)

## [1] 40

median(ccl5_mc5$ac50, na.rm=TRUE)

## [1] 35

## Format
ccl1_mc5$list <- "ccl1"
ccl5_mc5$list <- "ccl5"
mc5_lists_combined <- rbind(ccl1_mc5, ccl5_mc5)
mc5_lists_combined$log_ac50 <- log10(mc5_lists_combined$ac50)

## Plot
ggplot()+
  geom_density(data=mc5_lists_combined, aes(x=log_ac50, fill=list), alpha=0.25) +
  xlim(-5,5) +
  labs(y= NULL, x = "Log 10 AC50 (uM)") +
  theme_minimal()

ToxCast data is available for 38 out of the original 50 chemicals in the CCL1 list tested across 1067 endpoints compared to 69 out of the original 93 chemicals in the CCL5 list tested across 1200 endpoints.The median of ToxCast AC50 across chemicals in the CCL1 list was 40 uM whereas the median ToxCast AC50 in the CCL5 list was 35 uM.

5.2 Leveraging Assay Annotations

BPA is a known endocrine-disrupting chemical (EDC). The BPA mc5 can be filtered to examine endpoints annotated as estrogen receptor to assess target-specific potency.

Click here to reveal how to subset BPA processed data at ER endpoints.

## Load mc5 for BPA
bpa_mc5 <- tcplLoadData(lvl = 5, fld = "dtxsid", val = "DTXSID7020182", type = "mc", add.fld = TRUE)   

## Load annotations
assays <- tcplQueryAPI(resource = "assay")

## Subset annotations
er_assays <- assays[like(gene,"ESR1|ESR2")]

## Subset mc5
bpa_er_mc5 <- bpa_mc5[aeid %in% er_assays$aeid,]  

## Calculate median AC50
median(bpa_er_mc5$ac50, na.rm=TRUE)

## [1] 0.6501345

The median of ToxCast AC50 for BPA across estrogen receptor specific endpoints was 0.6501345 uM

5.3 Adminstered Equivalent Doses

The highest level assumption in the in vitro to in vivo extrapolation (IVIVE) approach employed here is that the in vitro bioactive concentration in a ToxCast assay endpoint is roughly equivalent to a human plasma concentration in vivo. For a review of IVIVE and HTTK models for it, please see: Breen et al, 2021

Using the target-specific potency derived above, consider extrapolating to a human administered equivalent dose using the simplified derivation below. Assuming steady-state kinetics in human plasma, AED values in mg/kg/day units can be calculated from bioactivity using the following equation:

\[\text{AED prediction = AC50 or LEC } (micromolar) * \frac{1 mg/kg/day}{Css(micromolar)} \]

Where the Css (steady-state concentration) values for the median and 95th individual based on Monte Carlo simulation of species-specific physiological parameters(Pearce et al. 2017) were generated using the 3-compartment steady state model.

Using the ctxR functions for the CTX Hazard API, retrieve the HTTK parameters from the High throughput toxicokinetics (httk) R package. httk optionally implements multiple models that can have increasing complexity based on data available (e.g., using pbtk model or including interindividual toxicokinetic variability).

## Load httk parameters for BPA
bpa_httk <- get_httk_data(DTXSID = 'DTXSID7020182')

Click here to preview the available HTTK parameters for BPA by API.

id	dtxsid	parameter	measuredText	measured	predictedText	predicted	units	model	reference	percentile	species	dataSourceSpecies	dataVersion	importDate
101171	DTXSID7020182	Css	0.0083	0.0083	1.114	1.1140	mg/L	PBTK	Wambaugh et al. (2018)	95%	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101172	DTXSID7020182	Css	0.0083	0.0083	0.5297	0.5297	mg/L	PBTK	Wambaugh et al. (2018)	50%	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101173	DTXSID7020182	Css	0.0083	0.0083	1.076	1.0760	mg/L	3compartmentss	Wambaugh et al. (2018)	95%	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101174	DTXSID7020182	Css	0.0083	0.0083	0.5116	0.5116	mg/L	3compartmentss	Wambaugh et al. (2018)	50%	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101175	DTXSID7020182	TK.Half.Life	0.19	0.1900	139.5	139.5000	hours	1compartment	Wambaugh et al. (2018)	NA	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101176	DTXSID7020182	Days.Css	NA	NA	112	112.0000	Days	PBTK	NA	NA	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101177	DTXSID7020182	Vd	1.4	1.4000	12.66	12.6600	L/kg	1compartment	Wambaugh et al. (2018)	NA	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101178	DTXSID7020182	Fup	0.7181	0.7181	NA	NA	NA	NA	https://doi.org/10.1093/toxsci/kft012	NA	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101179	DTXSID7020182	Clint	0	0.0000	NA	NA	uL/min/million hepatocytes	NA	https://doi.org/10.1093/toxsci/kft012	NA	Rat	Rat	NA	2024-06-13T16:53:14.622350Z
101180	DTXSID7020182	Css	NA	NA	3.357	3.3570	mg/L	PBTK	NA	95%	Human	Human	NA	2024-06-13T16:53:14.622350Z
101181	DTXSID7020182	Css	NA	NA	0.4776	0.4776	mg/L	PBTK	NA	50%	Human	Human	NA	2024-06-13T16:53:14.622350Z
101182	DTXSID7020182	Css	NA	NA	3.357	3.3570	mg/L	3compartmentss	NA	95%	Human	Human	NA	2024-06-13T16:53:14.622350Z
101183	DTXSID7020182	Css	NA	NA	0.4778	0.4778	mg/L	3compartmentss	NA	50%	Human	Human	NA	2024-06-13T16:53:14.622350Z
101184	DTXSID7020182	TK.Half.Life	NA	NA	39.54	39.5400	hours	1compartment	NA	NA	Human	Human	NA	2024-06-13T16:53:14.622350Z
101185	DTXSID7020182	Days.Css	NA	NA	4	4.0000	Days	PBTK	NA	NA	Human	Human	NA	2024-06-13T16:53:14.622350Z
101186	DTXSID7020182	Vd	NA	NA	6.337	6.3370	L/kg	1compartment	NA	NA	Human	Human	NA	2024-06-13T16:53:14.622350Z
101187	DTXSID7020182	Fup	0.0385	0.0385	NA	NA	NA	NA	https://doi.org/10.1093/toxsci/kfz205	NA	Human	Human	NA	2024-06-13T16:53:14.622350Z
101188	DTXSID7020182	Clint	19.9	19.9000	NA	NA	uL/min/million hepatocytes	NA	https://doi.org/10.1093/toxsci/kfz205	NA	Human	Human	NA	2024-06-13T16:53:14.622350Z

Using the equation outlined above, considering the 95th percentile (more sensitive inter-individual toxicokinetic variability) estimate for steady-state plasma concentration (Css) using the 3-compartment steady state (3compartmentss) model, and the median AC50 for BPA in in vitro ER-related assay endpoints, extrapolate an AED:

Click here to show AED calculation for BPA.

\[ \frac{3.357 mg}{L} * \frac{g}{1000 mg} * \frac{mol}{228.29 g} * \frac{1e6 μmol}{mol} = \frac{14.705 μmol}{L} = 14.705 μm \]

\[ 0.6501345 μm * \frac{1 mg/kg/day}{14.705 μm} = 11.634 mg/kg/day \]

With the AED for BPA computed, consider deriving a Bioactivity:Exposure Ratio (BER).

## Load exposure predictions for BPA by demographic
bpa_demographic_exposure_prediction <- get_demographic_exposure_prediction(DTXSID = 'DTXSID7020182')

Click here to preview general exposure prediction for BPA.

id	dtxsid	demographic	predictor	median	medianText	l95	l95Text	u95	u95Text	units	ad	reference	dataVersion	importDate
768361	DTXSID7020182	Total	Food.Contact	0.0176600	0.01766	NA	NA	NA	NA	mg/kg/day	1	Biryol 2017	NA	2024-06-13T19:25:16.277317Z
769393	DTXSID7020182	Total	FINE	0.0000095	9.46e-06	NA	NA	NA	NA	mg/day	1	Shin 2012	NA	2024-06-13T19:25:16.277317Z
772655	DTXSID7020182	Total	RAIDAR	3.7700000	3.77	NA	NA	NA	NA	mg/kg/day	1	Arnot 2008	NA	2024-06-13T19:25:16.277317Z
784083	DTXSID7020182	Total	USETox.Pest	0.0562400	0.05624	NA	NA	NA	NA	intake fraction	1	Fantke 2013	NA	2024-06-13T19:25:16.277317Z
785935	DTXSID7020182	Total	USETox.Indust	0.0001372	0.0001372	NA	NA	NA	NA	intake fraction	1	Rosenbaum 2008	NA	2024-06-13T19:25:16.277317Z
749502	DTXSID7020182	Age 66+	SEEM2 Heuristic	0.0000661	6.60834995383669e-05	3e-07	2.7986341540408e-07	0.0194779	0.0194778699251516	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
751534	DTXSID7020182	BMI > 30	SEEM2 Heuristic	0.0000707	7.07304192271297e-05	3e-07	3.13621919723853e-07	0.0185761	0.0185760522525412	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
760855	DTXSID7020182	Total	SHEDS.Indirect	0.0000715	7.15e-05	NA	NA	NA	NA	mg/kg/day	1	Isaacs 2017	NA	2024-06-13T19:25:16.277317Z
761591	DTXSID7020182	Total	SHEDS.Direct	0.0000000	0	NA	NA	NA	NA	mg/kg/day	1	Isaacs 2017	NA	2024-06-13T19:25:16.277317Z
763267	DTXSID7020182	BMI <= 30	SEEM2 Heuristic	0.0000625	6.2450508333388e-05	3e-07	2.59182177179327e-07	0.0136211	0.0136211249503816	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
488214	DTXSID7020182	Total	SEEM3 Consensus	0.0000550	5.497e-05	2e-07	1.923e-07	0.0204400	0.02044	mg/kg/day	1	Ring 2018	NA	2024-06-13T19:25:16.277317Z
797784	DTXSID7020182	Total	USETox.Res	0.0439500	0.04395	NA	NA	NA	NA	intake fraction	1	Huang 2016	NA	2024-06-13T19:25:16.277317Z
807431	DTXSID7020182	Total	USETox.Diet	0.0001498	0.0001498	NA	NA	NA	NA	intake fraction	1	Ernstoff 2016	NA	2024-06-13T19:25:16.277317Z
709226	DTXSID7020182	Males	SEEM2 Heuristic	0.0000387	3.86795578537834e-05	3e-07	2.84671057884619e-07	0.0063062	0.00630617035849566	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
735410	DTXSID7020182	Age 12-19	SEEM2 Heuristic	0.0000587	5.87195691748974e-05	3e-07	2.80963221822448e-07	0.0171856	0.0171855959252902	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
697139	DTXSID7020182	Repro. Age Females	SEEM2 Heuristic	0.0000136	1.36427543462443e-05	1e-07	5.63723993835891e-08	0.0041766	0.00417661734132225	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
711258	DTXSID7020182	Females	SEEM2 Heuristic	0.0000124	1.24443070751952e-05	0e+00	4.90110833197268e-08	0.0028978	0.00289779809405841	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
737451	DTXSID7020182	Age 20-65	SEEM2 Heuristic	0.0000568	5.67594250809775e-05	2e-07	2.08028872989558e-07	0.0115093	0.0115092672875229	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z
723306	DTXSID7020182	Age 6-11	SEEM2 Heuristic	0.0000630	6.29620332442998e-05	3e-07	3.04991342892185e-07	0.0105371	0.0105370896882791	mg/kg/day	1	Wambaugh 2014	NA	2024-06-13T19:25:16.277317Z

6 Reproducibility

ToxCast provides a standard for consistent and reproducible data processing for diverse, targeted bioactivity assay data with readily available documentation and a unified FAIR software approach. As part of EPA’s commitment to gather and share its chemical data in open and transparent ways, all ToxCast chemical data is publicly available. For more information, visit the ToxCast Home Page

See tcpl’s vignette for more guidance on how ToxCast data are managed and how fields are defined. Data Downloads (out of scope for this vignette) allow users to set up their own personal instance of the invitrodb MySQL database and interact with the data directly via the tcpl R package. This is a preferred option for more customized or programmatic ToxCast data needs, or if users want to do their own data processing.

Here is information about R session used to generate this html document:

print(sessionInfo())

## R version 4.3.2 (2023-10-31 ucrt)
## Platform: x86_64-w64-mingw32/x64 (64-bit)
## Running under: Windows 11 x64 (build 22621)
## 
## Matrix products: default
## 
## 
## locale:
## [1] LC_COLLATE=English_United States.utf8 
## [2] LC_CTYPE=English_United States.utf8   
## [3] LC_MONETARY=English_United States.utf8
## [4] LC_NUMERIC=C                          
## [5] LC_TIME=English_United States.utf8    
## 
## time zone: America/New_York
## tzcode source: internal
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
## [1] kableExtra_1.4.0  ggplot2_3.4.4     dplyr_1.1.4       ctxR_1.0.0       
## [5] data.table_1.15.4 tcpl_3.1.0       
## 
## loaded via a namespace (and not attached):
##  [1] gtable_0.3.4        xfun_0.41           bslib_0.6.1        
##  [4] htmlwidgets_1.6.4   RMariaDB_1.3.1      numDeriv_2016.8-1.1
##  [7] crosstalk_1.2.1     vctrs_0.6.5         tools_4.3.2        
## [10] generics_0.1.3      curl_5.2.0          parallel_4.3.2     
## [13] tibble_3.2.1        fansi_1.0.6         RSQLite_2.3.4      
## [16] highr_0.10          chron_2.3-61        blob_1.2.4         
## [19] pkgconfig_2.0.3     proto_1.0.0         RColorBrewer_1.1-3 
## [22] lifecycle_1.0.4     farver_2.1.1        compiler_4.3.2     
## [25] stringr_1.5.1       munsell_0.5.0       htmltools_0.5.7    
## [28] sass_0.4.8          yaml_2.3.8          lazyeval_0.2.2     
## [31] plotly_4.10.4       pillar_1.9.0        jquerylib_0.1.4    
## [34] tcplfit2_0.1.6      tidyr_1.3.0         ellipsis_0.3.2     
## [37] cachem_1.0.8        gsubfn_0.7          tidyselect_1.2.0   
## [40] digest_0.6.34       stringi_1.8.3       purrr_1.0.2        
## [43] labeling_0.4.3      fastmap_1.1.1       grid_4.3.2         
## [46] colorspace_2.1-0    cli_3.6.2           sqldf_0.4-11       
## [49] magrittr_2.0.3      utf8_1.2.4          withr_3.0.0        
## [52] scales_1.3.0        bit64_4.0.5         rmarkdown_2.27     
## [55] httr_1.4.7          bit_4.0.5           gridExtra_2.3      
## [58] hms_1.1.3           memoise_2.0.1       evaluate_0.24.0    
## [61] knitr_1.45          viridisLite_0.4.2   rlang_1.1.3        
## [64] glue_1.7.0          DBI_1.2.0           xml2_1.3.6         
## [67] svglite_2.1.3       rstudioapi_0.15.0   jsonlite_1.8.8     
## [70] R6_2.5.1            systemfonts_1.0.5

ToxCast Tools for Users: Guided Use Case Examples

Madison Feshuk, Jason Brown, Carter Thunes, Sarah Davidson-Fritz, Katie Paul Friedman

Vignette for ASCCT ToxCast CE Course, October 29 2024