Developmental and Reproductive Toxicology (DART) Committee

 

Developmental and Reproductive Toxicology (DART) Committee

Mission Statement

The DART committee provides a forum where scientists from industry, government and academia can exchange information and initiate activities to advance science related to DART, and to develop consensus on the appropriate use of experimental data for human health risk assessment.

Announcements

Thyroid hormone assessment survey and historical control data collection

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology (DART) Technical Committee Thyroid Hormone Workgroup, in collaboration with the European Teratology Society (ETS) Thyroid Hormone Task Force, has initiated a comprehensive effort to survey and collect historical data for thyroid hormones measurements from nonclinical studies. Regulatory test guideline requirements for the measurement of thyroid hormones are already in place for several study types, and deliberations continue for other guidelines. This HESI DART-ETS joint effort aims to provide clarification and guidance regarding the collection, assessment and interpretation of thyroid hormone data for regulatory toxicology and risk assessment. The data collected will be anonymously archived in a database that will ultimately be available for public use and incorporated into a workshop planned for Spring 2019. The facility/laboratory, assay and strain-specific data collected will ultimately contribute to improved data interpretation, the establishment of biologically relevant ranges for each assessment and recommendations for best practices for thyroid assessment.

If your organization conducts these assays and you are interested participating in the survey and contributing to the data collection effort, please contact Connie Chen (cchen@hesiglobal.org) for more information.

Committee Contacts

HESI Staff

Connie Chen, PhD, MPH
cchen@hesiglobal.org

Leadership Team

Susan Makris, MS
US Environmental Protection Agency

Kary Thompson, PhD
Bristol-Myers Squibb

Members and Fact Sheet

Committee Resources

Committee SharePoint Site

Log-in here.

Committee Events

Rethinking Developmental Toxicity Testing: Evolution or Revolution

Washington, DC, USA

This workshop will consider new strategies to identify developmental hazards taking into account the current state of science which may include alternative possibilities or improvements to the current Segment 2 design. These considerations could include the use of new technology to overcome some of the limitations in predicting human response with current animal models or completely new radical approach to developmental toxicity hazard identification. These may range from having a critical paradigm to deciding when non-clinical studies are needed to the use of biotechnology and computational models or hazard characterization. Working groups can consider either strategy, or combinations of the two.

Read more

Labels Without Categories: A Workshop on FDA’s Pregnancy and Lactation Labeling Rule

Arlington, Virginia, USA

The recently finalized Pregnancy Labeling and Lactation Labeling Rule changes the organization of the current Pregnancy and Nursing Mothers section of the US package insert of prescription drugs. In response to these changes in prescription drug labeling, the HESI Developmental and Reproductive Toxicology (DART) Technical committee sponsored a two-day workshop on this topic.

Read more

WP_Query Object
(
    [query] => Array
        (
            [post_type] => event
            [posts_per_page] => 5
            [type] => 
            [area] => 
            [before] => 2050-01-01
            [after] => 
            [tags] => DART
            [showtitle] => false
            [meta_query] => Array
                (
                    [relation] => AND
                    [0] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2050-01-01
                            [compare] => <=
                        )

                )

            [paged] => 1
            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => post_tag
                            [field] => name
                            [terms] => DART
                        )

                )

            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
        )

    [query_vars] => Array
        (
            [post_type] => event
            [posts_per_page] => 5
            [type] => 
            [area] => 
            [before] => 2050-01-01
            [after] => 
            [tags] => DART
            [showtitle] => false
            [meta_query] => Array
                (
                    [relation] => AND
                    [0] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2050-01-01
                            [compare] => <=
                        )

                )

            [paged] => 1
            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => post_tag
                            [field] => name
                            [terms] => DART
                        )

                )

            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
            [error] => 
            [m] => 
            [p] => 0
            [post_parent] => 
            [subpost] => 
            [subpost_id] => 
            [attachment] => 
            [attachment_id] => 0
            [name] => 
            [static] => 
            [pagename] => 
            [page_id] => 0
            [second] => 
            [minute] => 
            [hour] => 
            [day] => 0
            [monthnum] => 0
            [year] => 0
            [w] => 0
            [category_name] => 
            [tag] => 
            [cat] => 
            [tag_id] => 107
            [author] => 
            [author_name] => 
            [feed] => 
            [tb] => 
            [meta_value] => 
            [preview] => 
            [s] => 
            [sentence] => 
            [title] => 
            [fields] => 
            [menu_order] => 
             => 
            [category__in] => Array
                (
                )

            [category__not_in] => Array
                (
                )

            [category__and] => Array
                (
                )

            [post__in] => Array
                (
                )

            [post__not_in] => Array
                (
                )

            [post_name__in] => Array
                (
                )

            [tag__in] => Array
                (
                )

            [tag__not_in] => Array
                (
                )

            [tag__and] => Array
                (
                )

            [tag_slug__in] => Array
                (
                )

            [tag_slug__and] => Array
                (
                )

            [post_parent__in] => Array
                (
                )

            [post_parent__not_in] => Array
                (
                )

            [author__in] => Array
                (
                )

            [author__not_in] => Array
                (
                )

            [ignore_sticky_posts] => 
            [suppress_filters] => 
            [cache_results] => 1
            [update_post_term_cache] => 1
            [lazy_load_term_meta] => 1
            [update_post_meta_cache] => 1
            [nopaging] => 
            [comments_per_page] => 50
            [no_found_rows] => 
        )

    [tax_query] => WP_Tax_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => post_tag
                            [terms] => Array
                                (
                                    [0] => DART
                                )

                            [field] => name
                            [operator] => IN
                            [include_children] => 1
                        )

                )

            [relation] => AND
            [table_aliases:protected] => Array
                (
                    [0] => wp_11_term_relationships
                )

            [queried_terms] => Array
                (
                    [post_tag] => Array
                        (
                            [terms] => Array
                                (
                                    [0] => DART
                                )

                            [field] => name
                        )

                )

            [primary_table] => wp_11_posts
            [primary_id_column] => ID
        )

    [meta_query] => WP_Meta_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [key] => _ilsi_date
                        )

                    [1] => Array
                        (
                            [0] => Array
                                (
                                    [key] => _ilsi_date
                                    [value] => 2050-01-01
                                    [compare] => <=
                                )

                            [relation] => OR
                        )

                    [relation] => AND
                )

            [relation] => AND
            [meta_table] => wp_11_postmeta
            [meta_id_column] => post_id
            [primary_table] => wp_11_posts
            [primary_id_column] => ID
            [table_aliases:protected] => Array
                (
                    [0] => wp_11_postmeta
                    [1] => mt1
                )

            [clauses:protected] => Array
                (
                    [wp_11_postmeta] => Array
                        (
                            [key] => _ilsi_date
                            [compare] => =
                            [compare_key] => =
                            [alias] => wp_11_postmeta
                            [cast] => CHAR
                        )

                    [mt1] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2050-01-01
                            [compare] => <=
                            [compare_key] => =
                            [alias] => mt1
                            [cast] => CHAR
                        )

                )

            [has_or_relation:protected] => 
        )

    [date_query] => 
    [request] => SELECT SQL_CALC_FOUND_ROWS  wp_11_posts.ID FROM wp_11_posts  LEFT JOIN wp_11_term_relationships ON (wp_11_posts.ID = wp_11_term_relationships.object_id) INNER JOIN wp_11_postmeta ON ( wp_11_posts.ID = wp_11_postmeta.post_id )  INNER JOIN wp_11_postmeta AS mt1 ON ( wp_11_posts.ID = mt1.post_id ) WHERE 1=1  AND ( 
  wp_11_term_relationships.term_taxonomy_id IN (107)
) AND ( 
  wp_11_postmeta.meta_key = '_ilsi_date' 
  AND 
  ( 
    ( mt1.meta_key = '_ilsi_date' AND mt1.meta_value <= '2050-01-01' )
  )
) AND wp_11_posts.post_type = 'event' AND (wp_11_posts.post_status = 'publish') GROUP BY wp_11_posts.ID ORDER BY wp_11_postmeta.meta_value DESC LIMIT 0, 5
    [posts] => Array
        (
            [0] => WP_Post Object
                (
                    [ID] => 20795
                     => 105
                     => 2019-01-10 10:45:01
                    [post_date_gmt] => 2019-01-10 15:45:01
                    [post_content] => 
				Thyroid Workshop_Logo1 (003)
	

Recent updates to OECD developmental/reproductive toxicology guidelines and other regulatory guidelines and guidance require the measurement of thyroid hormone levels in the blood of mammalian laboratory species during development.  Preliminary analyses indicate that there is a wide variability across laboratories in the methods being used to measure thyroid hormones in young rodents, as well as in the success of obtaining reliable data.  Even though publicly available regulatory guidelines and guidance address study design, they allow varied approaches to thyroid hormone measurement in rodents, and an optimal study design or logical approach to thyroid hormone testing in young rodents has not yet been established in a regulatory testing context.  Validity, accuracy, sensitivity and reproducibility of the assays are issues of concern.  It is not clear to what extent variability in the data can be attributed to methodological issues or to innate biological variability.

WORKSHOP AIMS

  1. Present the state-of-the-science on thyroid hormone assessments, specifically as it relates to preclinical methods and data collection, and identify gaps and knowledge as it relates to regulatory DART testing,
  2. Provide clarification and guidance regarding the collection (timing and methods), assessment (standardization and validation), and interpretation of thyroid hormone data (as it relates to adversity) for regulatory toxicology and risk assessment,
  3. Discuss and come to consensus on recommendations on how to improve data interpretation/understanding of thyroid changes and their relationship to adverse outcomes
dreamstime_s_127655942

WORKSHOP AGENDA

Click here to download the workshop agenda.

 

Session 1: Setting the Stage

The Thyroid Axis - Overview of Anatomy, Physiology, Regulation in Mammalian Systems
Mary Gilbert, U.S. EPA (Download presentation) An AOP Network for Thyroid Hormone Disruption and Adverse Outcomes
Kevin Crofton, R3Fellows, LLC (Download presentation) Mild Thyroid Dysfunction During Pregnancy; Consequences for Pregnancy Outcome and Fetal Development
Robin Peeters, Erasmus University (Download presentation)

 

Session 2: Methodologies & Interpretation

Pathology Endpoints: Evaluation of Thyrotoxicants in Animal Studies
Brent Walling, Charles River (Download presentation) Overview of In Vitro Assays to Investigate Chemicals for Thyroid-Axis Disrupting Potential
Michael Hornung, U.S. EPA (Download presentation)

 

Session 3: Global Thyroid Activities

Overview of Ongoing Thyroid Activities in the European Union and United States
Manon Beekhuijzen, Charles River (Download presentation) HESI DART - ETS Thyroid Hormone Survey - Results & the Path Forward
Pragati Coder, Charles River (Download presentation) [post_title] => HESI DART Committee Thyroid Hormone Assessment Workshop [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => hesi-dart-committee-thyroid-hormone-assessment-workshop [to_ping] => [pinged] => [post_modified] => 2019-05-20 12:41:23 [post_modified_gmt] => 2019-05-20 17:41:23 [post_content_filtered] => [post_parent] => 0 [guid] => http://hesiglobal.org/?post_type=event&p=20795 [menu_order] => 0 [post_type] => event [post_mime_type] => [comment_count] => 0 [filter] => raw ) [1] => WP_Post Object ( [ID] => 4892 => 28 => 2017-08-02 14:26:43 [post_date_gmt] => 2017-08-02 19:26:43 [post_content] => [post_title] => Best Practices in Interpreting Developmental Toxicity Data for Classification and Labeling [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => clp-cmr [to_ping] => [pinged] => [post_modified] => 2018-01-12 10:14:28 [post_modified_gmt] => 2018-01-12 15:14:28 [post_content_filtered] => [post_parent] => 0 [guid] => http://hesiglobal.org/?post_type=event&p=4892 [menu_order] => 0 [post_type] => event [post_mime_type] => [comment_count] => 0 [filter] => raw ) [2] => WP_Post Object ( [ID] => 4241 => 28 => 2016-09-29 12:07:01 [post_date_gmt] => 2016-09-29 17:07:01 [post_content] => [post_title] => Rethinking Developmental Toxicity Testing: Evolution or Revolution [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => rethinkingdevtox [to_ping] => [pinged] => [post_modified] => 2017-05-04 14:50:17 [post_modified_gmt] => 2017-05-04 19:50:17 [post_content_filtered] => [post_parent] => 0 [guid] => http://hesiglobal.org/?post_type=event&p=4241 [menu_order] => 0 [post_type] => event [post_mime_type] => [comment_count] => 0 [filter] => raw ) [3] => WP_Post Object ( [ID] => 2065 => 12 => 2016-04-28 09:02:34 [post_date_gmt] => 2016-04-28 14:02:34 [post_content] => [post_title] => Pregnancy and Lactation Labeling Workshop [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => pregnancy-and-lactation-labeling-workshop [to_ping] => [pinged] => [post_modified] => 2016-04-28 09:19:40 [post_modified_gmt] => 2016-04-28 14:19:40 [post_content_filtered] => [post_parent] => 0 [guid] => https://ilsi.org/hesi/?post_type=event&p=2065 [menu_order] => 0 [post_type] => event [post_mime_type] => [comment_count] => 0 [filter] => raw ) [4] => WP_Post Object ( [ID] => 2418 => 12 => 2016-04-28 09:17:54 [post_date_gmt] => 2016-04-28 14:17:54 [post_content] => [post_title] => Labels Without Categories: A Workshop on FDA's Pregnancy and Lactation Labeling Rule [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => labels-without-categories-a-workshop-on-fdas-pregnancy-and-lactation-labeling-rule [to_ping] => [pinged] => [post_modified] => 2016-05-20 20:37:33 [post_modified_gmt] => 2016-05-21 01:37:33 [post_content_filtered] => [post_parent] => 0 [guid] => https://ilsi.org/hesi/?post_type=event&p=2418 [menu_order] => 0 [post_type] => event [post_mime_type] => [comment_count] => 0 [filter] => raw ) ) [post_count] => 5 [current_post] => -1 [in_the_loop] => [post] => WP_Post Object ( [ID] => 20795 => 105 => 2019-01-10 10:45:01 [post_date_gmt] => 2019-01-10 15:45:01 [post_content] => Thyroid Workshop_Logo1 (003)

Recent updates to OECD developmental/reproductive toxicology guidelines and other regulatory guidelines and guidance require the measurement of thyroid hormone levels in the blood of mammalian laboratory species during development.  Preliminary analyses indicate that there is a wide variability across laboratories in the methods being used to measure thyroid hormones in young rodents, as well as in the success of obtaining reliable data.  Even though publicly available regulatory guidelines and guidance address study design, they allow varied approaches to thyroid hormone measurement in rodents, and an optimal study design or logical approach to thyroid hormone testing in young rodents has not yet been established in a regulatory testing context.  Validity, accuracy, sensitivity and reproducibility of the assays are issues of concern.  It is not clear to what extent variability in the data can be attributed to methodological issues or to innate biological variability.

WORKSHOP AIMS

  1. Present the state-of-the-science on thyroid hormone assessments, specifically as it relates to preclinical methods and data collection, and identify gaps and knowledge as it relates to regulatory DART testing,
  2. Provide clarification and guidance regarding the collection (timing and methods), assessment (standardization and validation), and interpretation of thyroid hormone data (as it relates to adversity) for regulatory toxicology and risk assessment,
  3. Discuss and come to consensus on recommendations on how to improve data interpretation/understanding of thyroid changes and their relationship to adverse outcomes
dreamstime_s_127655942

WORKSHOP AGENDA

Click here to download the workshop agenda.

 

Session 1: Setting the Stage

The Thyroid Axis - Overview of Anatomy, Physiology, Regulation in Mammalian Systems
Mary Gilbert, U.S. EPA (Download presentation) An AOP Network for Thyroid Hormone Disruption and Adverse Outcomes
Kevin Crofton, R3Fellows, LLC (Download presentation) Mild Thyroid Dysfunction During Pregnancy; Consequences for Pregnancy Outcome and Fetal Development
Robin Peeters, Erasmus University (Download presentation)

 

Session 2: Methodologies & Interpretation

Pathology Endpoints: Evaluation of Thyrotoxicants in Animal Studies
Brent Walling, Charles River (Download presentation) Overview of In Vitro Assays to Investigate Chemicals for Thyroid-Axis Disrupting Potential
Michael Hornung, U.S. EPA (Download presentation)

 

Session 3: Global Thyroid Activities

Overview of Ongoing Thyroid Activities in the European Union and United States
Manon Beekhuijzen, Charles River (Download presentation) HESI DART - ETS Thyroid Hormone Survey - Results & the Path Forward
Pragati Coder, Charles River (Download presentation) [post_title] => HESI DART Committee Thyroid Hormone Assessment Workshop [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => hesi-dart-committee-thyroid-hormone-assessment-workshop [to_ping] => [pinged] => [post_modified] => 2019-05-20 12:41:23 [post_modified_gmt] => 2019-05-20 17:41:23 [post_content_filtered] => [post_parent] => 0 [guid] => http://hesiglobal.org/?post_type=event&p=20795 [menu_order] => 0 [post_type] => event [post_mime_type] => [comment_count] => 0 [filter] => raw ) [comment_count] => 0 [current_comment] => -1 [found_posts] => 15 [max_num_pages] => 3 [max_num_comment_pages] => 0 [is_single] => [is_preview] => [is_page] => [is_archive] => 1 [is_date] => [is_year] => [is_month] => [is_day] => [is_time] => [is_author] => [is_category] => [is_tag] => 1 [is_tax] => [is_search] => [is_feed] => [is_comment_feed] => [is_trackback] => [is_home] => [is_404] => [is_embed] => [is_paged] => [is_admin] => [is_attachment] => [is_singular] => [is_robots] => [is_posts_page] => [is_post_type_archive] => [query_vars_hash:WP_Query:private] => 650c109bd94a86ddf7020a7f0751cbf8 [query_vars_changed:WP_Query:private] => [thumbnails_cached] => [stopwords:WP_Query:private] => [compat_fields:WP_Query:private] => Array ( [0] => query_vars_hash [1] => query_vars_changed ) [compat_methods:WP_Query:private] => Array ( [0] => init_query_flags [1] => parse_tax_query ) )

Committee Publications

All Publications

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

This review is part of a multisector collaborative research effort coordinated by the HESI Developmental and Reproductive Toxicology (DART) Committee to increase the knowledge base in the nonclinical neonatal space to better inform clinical treatment decisions made for the newborn patient population (De Schaepdrijver et al., 2018).

Read more

Rethinking developmental toxicity testing: Evolution or revolution?

Summary from the HESI workshop on embryo‐fetal development testing, considers how we might design developmental toxicity testing if we started over with 21st century knowledge and techniques. The paper considers what might make current protocols more predictive for human risk.

Read more

Comparing rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on systemic dose and developmental effects

A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects between rat and rabbit study outcomes for individual compounds, EFDT studies in two species have added value over single studies.

Read more

Comparison of rat and rabbit embryo–fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects

Regulatory non-clinical safety testing of human pharmaceuticals typically requires embryo–fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of rabbit studies identifying an EFDT signal. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo–fetal death was observed more often in the rabbit. Discordance across species may be attributed to factors such as maternal toxicity, study design differences, pharmacokinetic differences, and pharmacologic relevance of species. The current analysis suggests that in general both species are equally sensitive on the basis of an overall EFDT LOAEL comparison, but selective EFDT toxicity in one species is not uncommon. Also, there appear to be species differences in the prevalence of various EFDT manifestations (i.e. embryo–fetal death, growth retardation, and dysmorphogenesis) between rat and rabbit, suggesting that the use of both species has a higher probability of detecting developmental toxicants than either one alone.

Read more

WP_Query Object
(
    [query] => Array
        (
            [post_type] => publication
            [posts_per_page] => 5
            [type] => 
            [area] => 
            [committee] => DART
            [authors] => true
            [showtitle] => 
            [meta_query] => Array
                (
                    [relation] => AND
                )

            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => ilsi_committee
                            [field] => name
                            [terms] => DART
                        )

                )

            [paged] => 1
            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
        )

    [query_vars] => Array
        (
            [post_type] => publication
            [posts_per_page] => 5
            [type] => 
            [area] => 
            [committee] => DART
            [authors] => true
            [showtitle] => 
            [meta_query] => Array
                (
                    [relation] => AND
                )

            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => ilsi_committee
                            [field] => name
                            [terms] => DART
                        )

                )

            [paged] => 1
            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
            [error] => 
            [m] => 
            [p] => 0
            [post_parent] => 
            [subpost] => 
            [subpost_id] => 
            [attachment] => 
            [attachment_id] => 0
            [name] => 
            [static] => 
            [pagename] => 
            [page_id] => 0
            [second] => 
            [minute] => 
            [hour] => 
            [day] => 0
            [monthnum] => 0
            [year] => 0
            [w] => 0
            [category_name] => 
            [tag] => 
            [cat] => 
            [tag_id] => 
            [author] => 
            [author_name] => 
            [feed] => 
            [tb] => 
            [meta_value] => 
            [preview] => 
            [s] => 
            [sentence] => 
            [title] => 
            [fields] => 
            [menu_order] => 
             => 
            [category__in] => Array
                (
                )

            [category__not_in] => Array
                (
                )

            [category__and] => Array
                (
                )

            [post__in] => Array
                (
                )

            [post__not_in] => Array
                (
                )

            [post_name__in] => Array
                (
                )

            [tag__in] => Array
                (
                )

            [tag__not_in] => Array
                (
                )

            [tag__and] => Array
                (
                )

            [tag_slug__in] => Array
                (
                )

            [tag_slug__and] => Array
                (
                )

            [post_parent__in] => Array
                (
                )

            [post_parent__not_in] => Array
                (
                )

            [author__in] => Array
                (
                )

            [author__not_in] => Array
                (
                )

            [ignore_sticky_posts] => 
            [suppress_filters] => 
            [cache_results] => 1
            [update_post_term_cache] => 1
            [lazy_load_term_meta] => 1
            [update_post_meta_cache] => 1
            [nopaging] => 
            [comments_per_page] => 50
            [no_found_rows] => 
            [taxonomy] => ilsi_committee
            [term_id] => DART
        )

    [tax_query] => WP_Tax_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => ilsi_committee
                            [terms] => Array
                                (
                                    [0] => DART
                                )

                            [field] => name
                            [operator] => IN
                            [include_children] => 1
                        )

                )

            [relation] => AND
            [table_aliases:protected] => Array
                (
                    [0] => wp_11_term_relationships
                )

            [queried_terms] => Array
                (
                    [ilsi_committee] => Array
                        (
                            [terms] => Array
                                (
                                    [0] => DART
                                )

                            [field] => name
                        )

                )

            [primary_table] => wp_11_posts
            [primary_id_column] => ID
        )

    [meta_query] => WP_Meta_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [key] => _ilsi_date
                        )

                    [relation] => OR
                )

            [relation] => AND
            [meta_table] => wp_11_postmeta
            [meta_id_column] => post_id
            [primary_table] => wp_11_posts
            [primary_id_column] => ID
            [table_aliases:protected] => Array
                (
                    [0] => wp_11_postmeta
                )

            [clauses:protected] => Array
                (
                    [wp_11_postmeta] => Array
                        (
                            [key] => _ilsi_date
                            [compare] => =
                            [compare_key] => =
                            [alias] => wp_11_postmeta
                            [cast] => CHAR
                        )

                )

            [has_or_relation:protected] => 
        )

    [date_query] => 
    [request] => SELECT SQL_CALC_FOUND_ROWS  wp_11_posts.ID FROM wp_11_posts  LEFT JOIN wp_11_term_relationships ON (wp_11_posts.ID = wp_11_term_relationships.object_id) INNER JOIN wp_11_postmeta ON ( wp_11_posts.ID = wp_11_postmeta.post_id ) WHERE 1=1  AND ( 
  wp_11_term_relationships.term_taxonomy_id IN (233)
) AND ( 
  wp_11_postmeta.meta_key = '_ilsi_date'
) AND wp_11_posts.post_type = 'publication' AND (wp_11_posts.post_status = 'publish') GROUP BY wp_11_posts.ID ORDER BY wp_11_postmeta.meta_value DESC LIMIT 0, 5
    [posts] => Array
        (
            [0] => WP_Post Object
                (
                    [ID] => 21017
                     => 105
                     => 2019-03-07 13:55:43
                    [post_date_gmt] => 2019-03-07 18:55:43
                    [post_content] => 
                    [post_title] => Ontogeny of ADME Processes During Postnatal Development in Man and Preclinical Species: A Comprehensive Review
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => ontogeny-of-adme-processes-during-postnatal-development-in-man-and-preclinical-species-a-comprehensive-review
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2019-03-07 13:55:43
                    [post_modified_gmt] => 2019-03-07 18:55:43
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=21017
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [1] => WP_Post Object
                (
                    [ID] => 21018
                     => 105
                     => 2019-03-07 13:59:59
                    [post_date_gmt] => 2019-03-07 18:59:59
                    [post_content] => 
                    [post_title] => Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => physiology-of-the-neonatal-gastrointestinal-system-relevant-to-the-disposition-of-orally-administered-medications-2
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2019-03-07 14:50:43
                    [post_modified_gmt] => 2019-03-07 19:50:43
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=21018
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [2] => WP_Post Object
                (
                    [ID] => 7039
                     => 13
                     => 2018-06-06 09:47:38
                    [post_date_gmt] => 2018-06-06 14:47:38
                    [post_content] => 
                    [post_title] => Rethinking developmental toxicity testing: Evolution or revolution?
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => rethinking-developmental-toxicity-testing-evolution-or-revolution
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2018-06-06 09:47:38
                    [post_modified_gmt] => 2018-06-06 14:47:38
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=7039
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [3] => WP_Post Object
                (
                    [ID] => 4283
                     => 28
                     => 2016-10-21 11:44:43
                    [post_date_gmt] => 2016-10-21 16:44:43
                    [post_content] => 
                    [post_title] => Comparing rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on systemic dose and developmental effects
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => comparing-rat-and-rabbit-embryo-fetal-developmental-toxicity-data-for-379-pharmaceuticals-on-systemic-dose-and-developmental-effects
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2017-04-04 11:38:43
                    [post_modified_gmt] => 2017-04-04 16:38:43
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=4283
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [4] => WP_Post Object
                (
                    [ID] => 4284
                     => 28
                     => 2016-10-21 11:48:26
                    [post_date_gmt] => 2016-10-21 16:48:26
                    [post_content] => 
                    [post_title] => Comparison of rat and rabbit embryo–fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => comparison-of-rat-and-rabbit-embryo-fetal-developmental-toxicity-data-for-379-pharmaceuticals-on-the-nature-and-severity-of-developmental-effects
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2017-04-04 11:40:08
                    [post_modified_gmt] => 2017-04-04 16:40:08
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=4284
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

        )

    [post_count] => 5
    [current_post] => -1
    [in_the_loop] => 
    [post] => WP_Post Object
        (
            [ID] => 21017
             => 105
             => 2019-03-07 13:55:43
            [post_date_gmt] => 2019-03-07 18:55:43
            [post_content] => 
            [post_title] => Ontogeny of ADME Processes During Postnatal Development in Man and Preclinical Species: A Comprehensive Review
            [post_excerpt] => 
            [post_status] => publish
            [comment_status] => closed
            [ping_status] => closed
            [post_password] => 
            [post_name] => ontogeny-of-adme-processes-during-postnatal-development-in-man-and-preclinical-species-a-comprehensive-review
            [to_ping] => 
            [pinged] => 
            [post_modified] => 2019-03-07 13:55:43
            [post_modified_gmt] => 2019-03-07 18:55:43
            [post_content_filtered] => 
            [post_parent] => 0
            [guid] => http://hesiglobal.org/?post_type=publication&p=21017
            [menu_order] => 0
            [post_type] => publication
            [post_mime_type] => 
            [comment_count] => 0
            [filter] => raw
        )

    [comment_count] => 0
    [current_comment] => -1
    [found_posts] => 75
    [max_num_pages] => 15
    [max_num_comment_pages] => 0
    [is_single] => 
    [is_preview] => 
    [is_page] => 
    [is_archive] => 1
    [is_date] => 
    [is_year] => 
    [is_month] => 
    [is_day] => 
    [is_time] => 
    [is_author] => 
    [is_category] => 
    [is_tag] => 
    [is_tax] => 1
    [is_search] => 
    [is_feed] => 
    [is_comment_feed] => 
    [is_trackback] => 
    [is_home] => 
    [is_404] => 
    [is_embed] => 
    [is_paged] => 
    [is_admin] => 
    [is_attachment] => 
    [is_singular] => 
    [is_robots] => 
    [is_posts_page] => 
    [is_post_type_archive] => 
    [query_vars_hash:WP_Query:private] => fd8a24d7dfff753c785924f6fc0712c1
    [query_vars_changed:WP_Query:private] => 
    [thumbnails_cached] => 
    [stopwords:WP_Query:private] => 
    [compat_fields:WP_Query:private] => Array
        (
            [0] => query_vars_hash
            [1] => query_vars_changed
        )

    [compat_methods:WP_Query:private] => Array
        (
            [0] => init_query_flags
            [1] => parse_tax_query
        )

)