TSCA risk evaluation-directed characterization of occupational exposures during formaldehyde manufacturing, use as an intermediate, and compounding of formaldehyde-based polymers.

In 2020, the U.S. EPA initiated TSCA risk evaluations for 20 High Priority chemicals, as required by the Lautenberg Act. In addition to consumer exposures, the evaluations include quantitative assessments of worker exposures, hazards and risk. The EPA evaluations of worker exposures, and authority over corrective action to address unacceptably high workplace exposures, overlap OSHA's authority for regulating workplace exposures. This dual federal regulatory authority for risk evaluation and risk management, presents new challenges for industrial hygienists, exposure/risk assessors, and risk managers. One of the chemicals identified as High Priority by the EPA is formaldehyde. In response to these challenges, Celanese supplemented its regular OSHA compliance sampling for formaldehyde with a one-time comprehensive sampling at our sole U.S. formaldehyde manufacturing facility. The sampling characterized all worker populations at the facility, including office workers. Although the EPA assessment is ongoing and may reach different conclusions related to an acceptable exposure limit, 126 full-shift monitoring results demonstrated compliance with the OSHA Formaldehyde Standard (29 CRF 1910.1048) for health protection. Methodologies used to identify workers for exposure monitoring, to characterize multiple EPA-specified worker populations, as well as potential challenges related to the dual regulatory authority for assessing and managing worker exposures are discussed.

Considerations for refining the risk assessment process for formaldehyde: Results from an interdisciplinary workshop.

Anticipating the need to evaluate and integrate scientific evidence to inform new risk assessments or to update existing risk assessments, the Formaldehyde Panel of the American Chemistry Council (ACC), in collaboration with the University of North Carolina, convened a workshop: "Understanding Potential Human Health Cancer Risk - From Data Integration to Risk Evaluation" in October 2017. Twenty-four (24) invited-experts participated with expertise in epidemiology, toxicology, science integration and risk evaluation. Including members of the organizing committee, there were 29 participants. The meeting included eleven presentations encompassing an introduction and three sessions: (1) "integrating the formaldehyde science on nasal/nasopharyngeal carcinogenicity and potential for causality"; (2) "integrating the formaldehyde science on lymphohematopoietic cancer and potential for causality; and, (3) "formaldehyde research-data suitable for risk assessment". Here we describe key points from the presentations on epidemiology, toxicology and mechanistic studies that should inform decisions about the potential carcinogenicity of formaldehyde in humans and the discussions about approaches for structuring an integrated, comprehensive risk assessment for formaldehyde. We also note challenges expected when attempting to reconcile divergent results observed from research conducted within and across different scientific disciplines - especially toxicology and epidemiology - and in integrating diverse, multi-disciplinary mechanistic evidence.

Use of the RISK21 roadmap and matrix: human health risk assessment of the use of a pyrethroid in bed netting.

The HESI-coordinated RISK21 roadmap and matrix are tools that provide a transparent method to compare exposure and toxicity information and assess whether additional refinement is required to obtain the necessary precision level for a decision regarding safety. A case study of the use of a pyrethroid, "pseudomethrin," in bed netting to control malaria is presented to demonstrate the application of the roadmap and matrix. The evaluation began with a problem formulation step. The first assessment utilized existing information pertaining to the use and the class of chemistry. At each stage of the step-wise approach, the precision of the toxicity and exposure estimates were refined as necessary by obtaining key data which enabled a decision on safety to be made efficiently and with confidence. The evaluation demonstrated the concept of using existing information within the RISK21 matrix to drive the generation of additional data using a value-of-information approach. The use of the matrix highlighted whether exposure or toxicity required further investigation and emphasized the need to address the default uncertainty factor of 100 at the highest tier of the evaluation. It also showed how new methodology such as the use of in vitro studies and assays could be used to answer the specific questions which arise through the use of the matrix. The matrix also serves as a useful means to communicate progress to stakeholders during an assessment of chemical use.

Transgenic proteins in agricultural biotechnology: The toxicology forum 40th annual summer meeting.

During the 40th Annual Meeting of The Toxicology Forum, the current and potential future science, regulations, and politics of agricultural biotechnology were presented and discussed. The range of current commercial crops and commercial crop traits related to transgenic proteins were reviewed and example crop traits discussed, including insecticidal resistance conferred by Bt proteins and the development of nutritionally enhanced food such as Golden Rice. The existing regulatory framework in the USA, with an emphasis on US FDA's role in evaluating the safety of genetically engineered crops under the regulatory umbrella of the FD&C Act was reviewed. Consideration was given to the polarized politics surrounding agricultural biotechnology, the rise of open access journals, and the influence of the internet and social media in shaping public opinion. Numerous questions related to misconceptions regarding current products and regulations were discussed, highlighting the need for more scientists to take an active role in public discourse to facilitate public acceptance and adoption of new technologies and to enable science-based regulations.

RNAi technologies in agricultural biotechnology: The Toxicology Forum 40th Annual Summer Meeting.

During the 40th Annual Meeting of The Toxicology Forum, the current and potential future science, regulations, and politics of agricultural biotechnology were presented and discussed. The meeting session described herein focused on the technology of RNA interference (RNAi) in agriculture. The general process by which RNAi works, currently registered RNAi-based plant traits, example RNAi-based traits in development, potential use of double stranded RNA (dsRNA) as topically applied pesticide active ingredients, research related to the safety of RNAi, biological barriers to ingested dsRNA, recent regulatory RNAi science reviews, and regulatory considerations related to the use of RNAi in agriculture were discussed. Participants generally agreed that the current regulatory framework is robust and appropriate for evaluating the safety of RNAi employed in agricultural biotechnology and were also supportive of the use of RNAi to develop improved crop traits. However, as with any emerging technology, the potential range of future products, potential future regulatory frameworks, and public acceptance of the technology will continue to evolve. As such, continuing dialogue was encouraged to promote education of consumers and science-based regulations.

A 28-day oral toxicity evaluation of small interfering RNAs and a long double-stranded RNA targeting vacuolar ATPase in mice.

New biotechnology-derived crop traits have been developed utilizing the natural process of RNA interference (RNAi). However, plant-produced double stranded RNAs (dsRNAs) are not known to present a hazard to mammals because numerous biological barriers limit uptake and potential for activity. To evaluate this experimentally, dsRNA sequences matching the mouse vATPase gene (an established target for control of corn rootworms) were evaluated in a 28-day toxicity study with mice. Test groups were orally gavaged with escalating doses of either a pool of four 21-mer vATPase small interfering RNAs (siRNAs) or a 218-base pair vATPase dsRNA. There were no treatment-related effects on body weight, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. The highest dose levels tested were considered to be the no observed adverse effect levels (NOAELs) for the 21-mer siRNAs (48 mg/kg/day) and the 218 bp dsRNA (64 mg/kg/day). As an additional exploratory endpoint, vATPase gene expression, was evaluated in selected gastrointestinal tract and systemic tissues. The results of this assay did not indicate treatment-related suppression of vATPase. The results of this study indicate that orally ingested dsRNAs, even those targeting a gene in the test species, do not produce adverse health effects in mammals.

Consensus diagnoses and mode of action for the formation of gastric tumors in rats treated with the chloroacetanilide herbicides alachlor and butachlor.

A panel of pathologists (Panel) was formed to evaluate the pathogenesis and human relevance of tumors that developed in the fundic region of rat stomachs in carcinogenicity and mechanistic studies with alachlor and butachlor. The Panel evaluated stomach sections stained with hematoxylin and eosin, neuron-specific enolase, and chromogranin A to determine the presence and relative proportion of enterochromaffin-like (ECL) cells in the tumors and concluded all tumors were derived from ECL cells. Biochemical and pathological data demonstrated the tumor formation involved a nongenotoxic threshold mode of action (MOA) initially characterized by profound atrophy of the glandular fundic mucosa that affected gastric glands, but not surface epithelium. This resulted in a substantial loss of parietal cells and a compensatory mucosal cell proliferation. The loss of parietal cells caused a marked increase in gastric pH (hypochlorhydria), leading to sustained and profound hypergastrinemia. The mucosal atrophy, together with the increased gastrin, stimulated cell growth in one or more ECL cell populations, resulting in neoplasia. ECL cell autocrine and paracrine effects led to dedifferentiation of ECL cell tumors. The Panel concluded the tumors develop via a threshold-dependent nongenotoxic MOA, under conditions not relevant to humans.

The Use of Behavioral Skills Training to Teach Components of Direct Instruction.

Behavioral skills training (BST) has been demonstrated to be an effective method for training staff to perform skills with high fidelity in a relatively short amount of time. In the current study, three components of direct instruction (DI) were trained using BST. The participants were two classroom instructors with prior experience implementing DI with students with autism. The targets for staff training were accuracy with signal delivery, error correction, and delivery of praise. A multiple-baseline design across skills was used to evaluate the effects of BST for each participant. Generalization probes were conducted with a student with autism during baseline and after mastery with each skill was demonstrated. BST rapidly increased staff performance across skills, with generalization demonstrated during classroom probes. This study extends the use of BST to training staff to implement DI, and the results suggest that BST resulted in improved teacher performance of the targeted skills during generalization probes with students.

Evaluation of a telehealth parent training program in teaching self-care skills to children with autism.

The present study used synchronous video conferencing to remotely deliver a behavioral skills training-based (BST) parent training program to 3 parents of children with autism in the family home. Parents were taught to implement graduated guidance to teach their children several important self-care skills. Parents did not correctly implement graduated guidance after receiving detailed written instructions only. After parents received the BST parent training package, however, all parents implemented graduated guidance with near-perfect levels of fidelity, and all children completed the targeted self-care skills with substantially higher levels of accuracy and independence. Furthermore, parents reported high levels of satisfaction with graduated guidance, the telehealth BST training package, and their children's ability to complete self-care skills.

Wind-bias correction method for narrowband sodium Doppler lidars using iodine absorption spectroscopy.

We present a technique to measure the frequency chirp introduced by the laser pulse amplification process in the transmitter of the Colorado State University sodium lidar system. This chirp causes a systematic radial wind bias that must be removed from the reported wind measurements. An iodine absorption line located near the lidar operating wavelength of 589.16 nm is used for real-time monitoring and measurement of the chirp for the correction of radial wind bias. This technique has been thoroughly characterized in the laboratory and validated by field testing, facilitating simultaneous measurements of temperature and horizontal wind in the mesopause region of the atmosphere (80-105 km).

Derivation of safe exposure levels for potential migration of formaldehyde into food.

Polyoxymethylene (POM) is a polymer of formaldehyde used inter alia for kitchenware and food processing machines. By migration into food, consumers may be exposed to small additional amounts of formaldehyde in food. In order to address such potential exposures, Specific Migration Limits are derived using all studies with oral exposure in mammals and birds. The assessment is not only based on local irritation observed in a 2-year rat study that has previously served to calculate acceptable exposure levels, but also on systemic effects, namely on effects on the kidney in adult rats and testes in birds before sexual maturity. At the relatively high oral exposure levels (up to 2000 ppm in drinking water) long-term effects caused by formic acid, the first step metabolite of formaldehyde, such as acidosis, cannot be excluded. The lowest Specific Migration Limit of 2.74 mg/dm2, corresponding to 16.5 mg formaldehyde/kg food, is based upon kidney effects in rats, leading to potential exposures that range between 2900 and 4400 times below the endogenous turnover of formaldehyde. Lastly, a recent migration study with POM showed that migration of formaldehyde into food simulants is over an order of magnitude below the lowest Specific Migration Limit derived herein.

A global view on the effect of water uptake on aerosol particle light scattering.

A reference dataset of multi-wavelength particle light scattering and hemispheric backscattering coefficients for different relative humidities (RH) between RH = 30 and 95% and wavelengths between λ = 450 nm and 700 nm is described in this work. Tandem-humidified nephelometer measurements from 26 ground-based sites around the globe, covering multiple aerosol types, have been re-analysed and harmonized into a single dataset. The dataset includes multi-annual measurements from long-term monitoring sites as well as short-term field campaign data. The result is a unique collection of RH-dependent aerosol light scattering properties, presented as a function of size cut. This dataset is important for climate and atmospheric model-measurement inter-comparisons, as a means to improve model performance, and may be useful for satellite and remote sensing evaluation using surface-based, in-situ measurements.

Chronic eosinophilic pneumonia: a case report and national survey.

Few reports of chronic eosinophilic pneumonia (CEP) in the pediatric population can be found in the literature. Our patient, a 16-year-old male subject presenting with signs and symptoms of CEP, prompted a survey of pediatric pulmonary training centers in the United States to determine the prevalence of eosinophilic pneumonia. The survey showed a low prevalence of acute eosinophilic pneumonia and CEP in the pediatric population, with an overall male/female ratio of 1.6:1.

Accuracy of three electronic monitors for metered-dose inhalers.

BACKGROUND: Prior studies indicate that some devices used to monitor metered-dose inhaler (MDI) use are not accurate. OBJECTIVE: To assess the accuracy of the Doser CT (NEW-MED Corporation; Waltham, MA), the MDILog (Medtrac Technologies; Lakewood, CO), and the SmartMist (Aradigm Corporation; Hayward, CA) in a bench-top study. DESIGN: One, two, and four puffs of fluticasone propionate MDI (Flovent; GlaxoWellcome; Research Triangle Park, NC) were actuated twice daily for 30 days with two units of each device. The date and time of each actuation were recorded in a log and then compared with the output of the device. The percentage of doses recorded accurately was compared by analysis of variance. MEASUREMENTS AND RESULTS: The SmartMist was 100% accurate, while both the Doser CT and MDILog devices occasionally recorded spurious actuations. The Doser CT also had missed actuations after the counter had prematurely reached zero secondary to the spurious recordings. The accuracy (mean plus minus SD) was 94.3 plus minus 2.9% for the Doser CT and 90.1 plus minus 6.9% for the MDILog (p = 0.21). The dose regimen actuated and duration of use did not significantly affect accuracy. CONCLUSION: All three devices are sufficiently accurate to monitor adherence in most clinical settings.

Managed care organizational characteristics and health care use among children with special health care needs.

OBJECTIVE: To examine the relationship between features of managed care organizations (MCOs) and health care use patterns by children. DATA SOURCES: Telephone survey data from 2,223 parents of children with special health care needs, MCO-administrator interview data, and health care claims data. STUDY DESIGN: Cross-sectional survey data from families about the number of consequences of their children's conditions and from MCO administrators about their plans' organizational features were used. Indices reflecting the MCO characteristics were developed using data reduction techniques. Hierarchical models were developed to examine the relationship between child sociodemographic and health characteristics and the MCO indices labeled: Pediatrician Focused (PF) Index, Specialist Focused (SF) Index, and Fee for Service (FFS) Index, and outpatient use rates and charges, inpatient admissions, emergency room (ER) visits, and specialty consultations. DATA COLLECTION/EXTRACTION METHODS: The telephone and MCO-administrator survey data were linked to the enrollment and claims files. PRINCIPAL FINDINGS: The child's age, gender, and condition consequences were consistent predictor variables related to health care use and charges. The PF Index was associated with decreased outpatient use rates and charges and decreased inpatient admissions. The SF Index was associated with increased ER visits and decreased specialty consultations, while the FFS Index was associated with increased outpatient use rates and charges. CONCLUSION: After controlling for sociodemographic and health characteristics, the PF, SF, and FFS indices were significantly associated with children's health care use patterns.

Behavioral interventions to reduce the pica of persons with developmental disabilities.

The consumption of nonfood items (i.e., pica) frequently occurs in persons with developmental disabilities. Pica may result in the puncture or blockage of the digestive tract, infestation by gastrointestinal parasites, and can interfere with an individual's daily learning, occupational performance, and quality of life. Twenty-six published studies have examined the efficacy of behavioral-intervention packages (e.g., differential reinforcement of other behavior, noncontingent attention, or overcorrection) on the pica of persons with developmental disabilities. This article reviews those studies and discusses the effectiveness, generality, and acceptability of the various intervention packages used to reduce pica. Additionally, this article highlights the recent clinical advancements that have been made in the treatment of the pica of persons with developmental disabilities.

Observational effects on the preferences of children with autism.

Children with an autism spectrum disorder (ASD) may play with limited objects or toys, making it difficult for teachers to identify reinforcers to use in teaching new skills. The goal of this study was to alter children's preferences from highly preferred toys to toys that were originally less preferred using an observational pairing procedure. Child participants observed a preferred adult playing with toys that were initially less preferred by the child. This intervention resulted in a shift in preference toward the item manipulated by the adult. Maintenance of the changed preference was idiosyncratic across participants. Results suggest a procedure for expanding the range of items that students with ASD will select.

Comparing the teaching interaction procedure to social stories for people with autism.

This study compared social stories and the teaching interaction procedure to teach social skills to 6 children and adolescents with an autism spectrum disorder. Researchers taught 18 social skills with social stories and 18 social skills with the teaching interaction procedure within a parallel treatment design. The teaching interaction procedure resulted in mastery of all 18 skills across the 6 participants. Social stories, in the same amount of teaching sessions, resulted in mastery of 4 of the 18 social skills across the 6 participants. Participants also displayed more generalization of social skills taught with the teaching interaction procedure to known adults and peers.

Comparison of simultaneous prompting and no-no prompting in two-choice discrimination learning with children with autism.

This study compared no-no prompting procedures to simultaneous prompting procedures for 3 children with autism. Using a parallel treatments design, researchers taught rote math skills, receptive labels, or answers to "wh-" questions with both prompting systems. Results indicated that no-no prompting was effective in teaching all skills. By contrast, simultaneous prompting was effective in teaching only one pair of skills to 1 participant in the same amount of teaching time and trials. Researchers conducted a preference assessment to determine which of the two prompting procedures the 3 participants preferred. The participants showed mixed preferences for the two procedures.