Peer-Reviewed Publications

All Publications

Using exposure bands for rapid decision making in the RISK21 tiered exposure assessment

The ILSI Health and Environmental Sciences Institute (HESI) Risk Assessment in the Twenty-first Century (RISK21) project was initiated to address and catalyze improvements in human health risk assessment. RISK21 is a problem formulation-based conceptual roadmap and risk matrix visualization tool, facilitating transparent evaluation of both hazard and exposure components. The RISK21 roadmap is exposure-driven, that is, exposure is used as the second step (after problem formulation) to define and focus the assessment. This paper describes the exposure tiers of the RISK21 matrix and the approaches to adapt readily available information to more quickly inform exposure at a screening level. In particular, exposure look-up tables were developed from available exposure tools (European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) for worker exposure, ECETOC TRA, European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) for consumer exposure, and USEtox® for indirect exposure to humans via the environment) and were tested in a hypothetical mosquito bed netting case study. A detailed WHO risk assessment for a similar mosquito net use served as a benchmark for the performance of the RISK21 approach. The case study demonstrated that the screening methodologies provided suitable conservative exposure estimates for risk assessment. The results of this effort showed that the RISK21 approach is useful for defining future assessment efforts, focusing assessment activities and visualizing results.

Please click here to view the full citation.

Read more

Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability

This article characterizes a time course model of inflammation and hemostatic activation in rats treated with bacterial endotoxin (lipopolysaccharide, LPS) through a combination of traditional histologic and clinicopathologic endpoints and analyses of novel circulating biomarkers, including microRNA (miRNA) and extracellular vesicle (EV) profiles.

Read more

An evaluation of the utility of LVdP/dt40, QA interval, LVdP/dtmin and Tau as indicators of drug-induced changes in contractility and lusitropy in dogs

The importance of drug-induced effects on the inotropic state of the heart is well known. Unlike hemodynamic and cardiac electrophysiological methods, which have been routinely used in drug safety testing for years, the non-clinical assessment of drug effects on myocardial contractility is used less frequently with no established translation to humans. The goal of these studies was to determine whether assessment of alternate measures of cardiac inotropy could detect drug-induced changes in the contractile state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility. This study also evaluated drug-induced effects on lusitropy (relaxation) parameters of the heart.

 

Read more

Inter-laboratory optimization of protein extraction, separation, and fluorescent detection of endogenous rice allergens

In rice, several allergens have been identified such as the non-specific lipid transfer protein-1, the α-amylase/trypsin-inhibitors, the α-globulin, the 33 kDa glyoxalase I (Gly I), the 52–63 kDa globulin, and the granule-bound starch synthetase. The goal of the present study was to define optimal rice extraction and detection methods that would allow a sensitive and reproducible measure of several classes of known rice allergens. In a three-laboratory ring-trial experiment, several protein extraction methods were first compared and analyzed by 1D multiplexed SDS-PAGE. In a second phase, an inter-laboratory validation of 2D-DIGE analysis was conducted in five independent laboratories, focusing on three rice allergens (52 kDa globulin, 33 kDa glyoxalase I, and 14–16 kDa α-amylase/trypsin inhibitor family members). The results of the present study indicate that a combination of 1D multiplexed SDS-PAGE and 2D-DIGE methods would be recommended to quantify the various rice allergens.

Please click here to view this open access publication.

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

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

            [tax_query] => Array
                (
                )

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

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

            [tax_query] => Array
                (
                )

            [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] => 
        )

    [tax_query] => WP_Tax_Query Object
        (
            [queries] => Array
                (
                )

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

            [queried_terms] => Array
                (
                )

            [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] => =
                            [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  INNER JOIN wp_11_postmeta ON ( wp_11_posts.ID = wp_11_postmeta.post_id ) WHERE 1=1  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] => 4473
                     => 26
                     => 2017-02-14 15:25:33
                    [post_date_gmt] => 2017-02-14 20:25:33
                    [post_content] => 
                    [post_title] => Using exposure bands for rapid decision making in the RISK21 tiered exposure assessment
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => using-exposure-bands-for-rapid-decision-making-in-the-risk21-tiered-exposure-assessment
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2017-02-14 15:25:33
                    [post_modified_gmt] => 2017-02-14 20:25:33
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=4473
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [1] => WP_Post Object
                (
                    [ID] => 4423
                     => 13
                     => 2017-01-13 09:20:24
                    [post_date_gmt] => 2017-01-13 14:20:24
                    [post_content] => 
                    [post_title] => Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => 4423
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2017-01-18 13:18:28
                    [post_modified_gmt] => 2017-01-18 18:18:28
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=4423
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [2] => WP_Post Object
                (
                    [ID] => 4445
                     => 13
                     => 2017-01-18 09:53:12
                    [post_date_gmt] => 2017-01-18 14:53:12
                    [post_content] => 
                    [post_title] => An evaluation of the utility of LVdP/dt40, QA interval, LVdP/dtmin and Tau as indicators of drug-induced changes in contractility and lusitropy in dogs
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => an-evaluation-of-the-utility-of-lvdpdt40-qa-interval-lvdpdtmin-and-tau-as-indicators-of-drug-induced-changes-in-contractility-and-lusitropy-in-dogs
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2017-04-04 11:35:58
                    [post_modified_gmt] => 2017-04-04 16:35:58
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=4445
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [3] => WP_Post Object
                (
                    [ID] => 4405
                     => 26
                     => 2017-01-09 14:59:08
                    [post_date_gmt] => 2017-01-09 19:59:08
                    [post_content] => 
                    [post_title] => Inter-laboratory optimization of protein extraction, separation, and fluorescent detection of endogenous rice allergens
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => inter-laboratory-optimization-of-protein-extraction-separation-and-fluorescent-detection-of-endogenous-rice-allergens
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2017-01-09 15:00:21
                    [post_modified_gmt] => 2017-01-09 20:00:21
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => http://hesiglobal.org/?post_type=publication&p=4405
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [4] => 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
                )

        )

    [post_count] => 5
    [current_post] => -1
    [in_the_loop] => 
    [post] => WP_Post Object
        (
            [ID] => 4473
             => 26
             => 2017-02-14 15:25:33
            [post_date_gmt] => 2017-02-14 20:25:33
            [post_content] => 
            [post_title] => Using exposure bands for rapid decision making in the RISK21 tiered exposure assessment
            [post_excerpt] => 
            [post_status] => publish
            [comment_status] => closed
            [ping_status] => closed
            [post_password] => 
            [post_name] => using-exposure-bands-for-rapid-decision-making-in-the-risk21-tiered-exposure-assessment
            [to_ping] => 
            [pinged] => 
            [post_modified] => 2017-02-14 15:25:33
            [post_modified_gmt] => 2017-02-14 20:25:33
            [post_content_filtered] => 
            [post_parent] => 0
            [guid] => http://hesiglobal.org/?post_type=publication&p=4473
            [menu_order] => 0
            [post_type] => publication
            [post_mime_type] => 
            [comment_count] => 0
            [filter] => raw
        )

    [comment_count] => 0
    [current_comment] => -1
    [found_posts] => 349
    [max_num_pages] => 70
    [max_num_comment_pages] => 0
    [is_single] => 
    [is_preview] => 
    [is_page] => 
    [is_archive] => 
    [is_date] => 
    [is_year] => 
    [is_month] => 
    [is_day] => 
    [is_time] => 
    [is_author] => 
    [is_category] => 
    [is_tag] => 
    [is_tax] => 
    [is_search] => 
    [is_feed] => 
    [is_comment_feed] => 
    [is_trackback] => 
    [is_home] => 1
    [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] => 1927f7d2dbd55daef0655fe594864a08
    [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
        )

)