Teratology Studies on Lewisite and Sulfur Mustard Agents: Effects of Sulfur Mustard in Rats and Rabbits

Sulfur mustard (HD) was administered to rats and rabbits by intragastric intubation. Rats were dosed daily from 6 through 15 days of gestation (dg) with 0. 0.5, 1.0 or 2.0 mg of HD/kg; rabbits were dosed with 0, 0.4, 0.6 or 0.8 mg/kg on 6 through 19 dg. Maternal animals were weighed periodically and, at necropsy, were examined for gross lesions of major organs and reproductive performance; live fetuses were weighed and examined for external, internal and skeletal defects. In rats, reductions in body weights were observed in maternal animals and their female fetuses at the lowest administered dose (0.5 mg/kg), but the incidence of fetal malformations was not increased. In rabbits the highest administered dose (0.8 mg/kg) induced maternal mortality and depressed body weight measures but did not affect fetal development. These results suggest that orally administered HD is not teratogenic in rats and rabbits since fetal effects were observed only at dose levels that induced frank maternal toxicity. Estimations of dose ranges for "no observable effects levels" in rats and rabbits, respectively, were: 0.8 mg/kg in their fetuses

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventytwo Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality was observed. A significant decrease (P ( 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg/kg group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Lewisite in Rats Final Report

Occupational health standards have not been established for Lewisite [bis(2-chlorethyl)arsine], a potent toxic vesicant which reacts with the sulfhydryl groups of proteins through its arsenic group. The purposes of this study were to determine the reproductive consequences and dose~response of continuing Lewisite exposure of parental males and females and their offspring in a 42-week two-generation study. Solutions of Lewisite were prepared for administration by diluting the neat agent with sesame oil. Rats were administered Lewisite (0, 0.10, 0.25 or 0.60 mg/kg/day for 5 days a week) via intragastric intubation prior to mating, during mating and after mating until the birth of their offspring. The dams continued to receive Lewisite during lactation. At weaning, male and female offspring of each group were selected to continue on the study; rece1v1ng Lewisite during adolescence, mating and throughout gestation. Again, the dams continued to receive Lewisite until weaning of the offspring. Lewisite had no adverse effect on reproduction performance, fertility or reproductive organ weights of male or female rats through two consecutive generations. No adverse effect to offspring were attributed to Lewisite exposure. Minor changes in growth was the only maternal effect observed. Lewisite exposure of parental rats caused no gross or microscopic lesions in testes, epididymis, prostrate, seminal vesicles, ovaries, uterus or vagina. Severe inflammation of the lung was observed at necropsy in cases in which Lewisite gained access to the respiratory system from accidental dosing or reflux and aspiration; this usually caused early death of the animal. The NOEL for reproductive effects in this study was greater than 0.60 mg/kg/day

Highlights and outcomes of the 2021 Global Community Consultation

International collaboration between collections, aggregators, and researchers within the biodiversity community and beyond is becoming increasingly important in our efforts to support biodiversity, conservation and the life of the planet. The social, technical, logistical and financial aspects of an equitable biodiversity data landscape – from workforce training and mobilization of linked specimen data, to data integration, use and publication – must be considered globally and within the context of a growing biodiversity crisis. In recent years, several initiatives have outlined paths forward that describe how digital versions of natural history specimens can be extended and linked with associated data. In the United States, Webster (2017) presented the “extended specimen”, which was expanded upon by Lendemer et al. (2019) through the work of the Biodiversity Collections Network (BCoN). At the same time, a “digital specimen” concept was developed by DiSSCo in Europe (Hardisty 2020). Both the extended and digital specimen concepts depict a digital proxy of an analog natural history specimen, whose digital nature provides greater capabilities such as being machine-processable, linkages with associated data, globally accessible information-rich biodiversity data, improved tracking, attribution and annotation, additional opportunities for data use and cross-disciplinary collaborations forming the basis for FAIR (Findable, Accessible, Interoperable, Reproducible) and equitable sharing of benefits worldwide, and innumerable other advantages, with slight variation in how an extended or digital specimen model would be executed. Recognizing the need to align the two closely-related concepts, and to provide a place for open discussion around various topics of the Digital Extended Specimen (DES; the current working name for the joined concepts), we initiated a virtual consultation on the discourse platform hosted by the Alliance for Biodiversity Knowledge through GBIF. This platform provided a forum for threaded discussions around topics related and relevant to the DES. The goals of the consultation align with the goals of the Alliance for Biodiversity Knowledge: expand participation in the process, build support for further collaboration, identify use cases, identify significant challenges and obstacles, and develop a comprehensive roadmap towards achieving the vision for a global specification for data integration. In early 2021, Phase 1 launched with five topics: Making FAIR data for specimens accessible; Extending, enriching and integrating data; Annotating specimens and other data; Data attribution; and Analyzing/mining specimen data for novel applications. This round of full discussion was productive and engaged dozens of contributors, with hundreds of posts and thousands of views. During Phase 1, several deeper, more technical, or additional topics of relevance were identified and formed the foundation for Phase 2 which began in May 2021 with the following topics: Robust access points and data infrastructure alignment; Persistent identifier (PID) scheme(s); Meeting legal/regulatory, ethical and sensitive data obligations; Workforce capacity development and inclusivity; Transactional mechanisms and provenance; and Partnerships to collaborate more effectively. In Phase 2 fruitful progress was made towards solutions to some of these complex functional and technical long-term goals. Simultaneously, our commitment to open participation was reinforced, through increased efforts to involve new voices from allied and complementary fields. Among a wealth of ideas expressed, the community highlighted the need for unambiguous persistent identifiers and a dedicated agent to assign them, support for a fully linked system that includes robust publishing mechanisms, strong support for social structures that build trustworthiness of the system, appropriate attribution of legacy and new work, a system that is inclusive, removed from colonial practices, and supportive of creative use of biodiversity data, building a truly global data infrastructure, balancing open access with legal obligations and ethical responsibilities, and the partnerships necessary for success. These two consultation periods, and the myriad activities surrounding the online discussion, produced a wide variety of perspectives, strategies, and approaches to converging the digital and extended specimen concepts, and progressing plans for the DES -- steps necessary to improve access to research-ready data to advance our understanding of the diversity and distribution of life. Discussions continue and we hope to include your contributions to the DES in future implementation plans

Digital Extended Specimens: Enabling an Extensible Network of Biodiversity Data Records as Integrated Digital Objects on the Internet

The early twenty-first century has witnessed massive expansions in availability and accessibility of digital data in virtually all domains of the biodiversity sciences. Led by an array of asynchronous digitization activities spanning ecological, environmental, climatological, and biological collections data, these initiatives have resulted in a plethora of mostly disconnected and siloed data, leaving to researchers the tedious and time-consuming manual task of finding and connecting them in usable ways, integrating them into coherent data sets, and making them interoperable. The focus to date has been on elevating analog and physical records to digital replicas in local databases prior to elevating them to ever-growing aggregations of essentially disconnected discipline-specific information. In the present article, we propose a new interconnected network of digital objects on the Internet—the Digital Extended Specimen (DES) network—that transcends existing aggregator technology, augments the DES with third-party data through machine algorithms, and provides a platform for more efficient research and robust interdisciplinary discovery

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

Occupational health standards have not been established for sulfur mustard (HD) [bis{2-chloroethyl)-sulfide) ' a strong alkylating agent with known mutagenic properties. Little, however, is known about the mutagenic activity of HD in mammalian species and data regarding the dominant lethal effects of HD are ambiguous. The purpose of this study was to determine the dominant lethal effect in male and female rats orally exposed to HD. The study was conducted in two phases; a female dominant lethal phase and a male dominant lethal phase. Sprague-Dawley rats of each sex were administered 0.08, 0.20, or 0.50 mg/kg HD in sesame oil 5 days/week for 10 weeks. For the female phase, treated or untreated males were mated with treated females and their fetuses were evaluated at approximately 14 days after copulation. For the male dominant lethal phase, treated males cohabited with untreated femal (during 5 days of each week for 10 weeks) and females were sacrificed for fetal evaluation 14 days after the midweek of cohabitation during each of the 10 weeks. The appearance and behavior of the rats were unremarkable throughout the experiment and there were no treatment-related deaths. Growth rates were reduced in both female and male rats treated with 0.50 mg/kg HD. Indicators of reproductive performance did not demonstrate significant female dominant lethal effects, although significant male dominant lethal effects were observed at 2 and 3 week post-exposure. These effects included increases of early fetal resorptions and preimplantation losses and decreases of total live embryo implants. These effects were most consistently observed at a dose of 0.50 mg/kg, but frequently occurred at the lower doses. Although no treatment-related effects on male reproductive organ weights or sperm motility were found, a significant increase in the percentage of abnormal sperm was detected in males exposed to 0. 50 mg/kg HD. The timing of these effects is consistent with an effect during the postmeiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids

Modeling lung cancer risks in laboratory dogs exposed to inhaled plutonium

These analyses are based on data from a lifespan study of beagle dogs exposed to inhaled plutonium being conducted at Pacific Northwest Laboratory. An important goal of this study is to increase understanding of health risk resulting from this exposure, with particular attention to lung cancer risks. Data on humans exposed to plutonium are inadequate for achieving this goal

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Lewisite in Rats Final Report

Occupational health standards have not been established for Lewisite [bis(2-chlorethyl)arsine], a potent toxic vesicant which reacts with the sulfhydryl groups of proteins through its arsenic group. The purposes of this study were to determine the reproductive consequences and dose~response of continuing Lewisite exposure of parental males and females and their offspring in a 42-week two-generation study. Solutions of Lewisite were prepared for administration by diluting the neat agent with sesame oil. Rats were administered Lewisite (0, 0.10, 0.25 or 0.60 mg/kg/day for 5 days a week) via intragastric intubation prior to mating, during mating and after mating until the birth of their offspring. The dams continued to receive Lewisite during lactation. At weaning, male and female offspring of each group were selected to continue on the study; rece1v1ng Lewisite during adolescence, mating and throughout gestation. Again, the dams continued to receive Lewisite until weaning of the offspring. Lewisite had no adverse effect on reproduction performance, fertility or reproductive organ weights of male or female rats through two consecutive generations. No adverse effect to offspring were attributed to Lewisite exposure. Minor changes in growth was the only maternal effect observed. Lewisite exposure of parental rats caused no gross or microscopic lesions in testes, epididymis, prostrate, seminal vesicles, ovaries, uterus or vagina. Severe inflammation of the lung was observed at necropsy in cases in which Lewisite gained access to the respiratory system from accidental dosing or reflux and aspiration; this usually caused early death of the animal. The NOEL for reproductive effects in this study was greater than 0.60 mg/kg/day