The collaborative development through multidisciplinary and advocate consensus of an accessible notice of rights for people with intellectual disabilities in police custody.

Background People with intellectual disabilities are over-represented in the criminal justice system. The United Nations' Convention on the Rights of Persons with Disabilities (UNCRPD) enshrines a right to equal access to justice for persons with disabilities (Article 13, UNCRPD). Accessible information is a key aspect of exercising this right. Yet, many jurisdictions, including Ireland, are yet to develop accessible information for disabled people who may be arrested. Aims This paper describes the collaborative development through multidisciplinary and advocate consensus of an accessible (Easy -to- Read) Notice of Rights (ERNR) for people with intellectual disabilities in police custody in Ireland. Methods Guidelines developed by Ireland's representative organisation for people with intellectual disabilities and examples of international practice were used to develop a draft ERNR by the primary researcher in partnership with an expert from a representative organisation for people with intellectual disabilities. The ERNR was developed thereafter through two focus groups with a view to achieving consensus with a focus on accessibility, accuracy and layout. This included a multidisciplinary focus group with participants from a representative organisation for people with intellectual disabilities, psychology, speech and language therapy, the police force, public health, forensic psychiatry, mental health, law and, subsequently, a focus group of people with lived experience of intellectual disability. Results Progressive development of the ERNR resulted in incremental improvements in textual accuracy as well as the inclusion of more accessible language and imagery. Originality/value This is the first attempt at developing an easy-to-read document relating to the legal rights of suspects in police custody in Ireland and, accordingly, this procedural innovation promises to assist, not just persons with intellectual disabilities, but also those with limited literacy at the point of arrest. The methodology used in the preparation of the document, employing a focus group to achieve consensus with participation from both multiple disciplines and persons with an intellectual disability, is in harmony with the ethos of the UNCPRD. This methodology may usefully be employed by other member states that have ratified the Convention but have yet to develop accessible version of the legal rights and entitlements that extend to arrested persons under their domestic law.

Genotoxicity and neonatal subchronic toxicity assessment of a novel mixture of the human-identical milk oligosaccharides lacto-N-fucopentaose I and 2'-fucosyllactose.

Human milk oligosaccharides (HMOs) are a complex group of bioactive molecules largely observed in human breast milk but also occurring in limited amounts in other mammalian milks. Advances in biotechnology have enabled production of human-identical milk oligosaccharides (HiMOs), structurally identical molecules to HMOs found naturally in human milk, intended for addition to infant formula to more closely replicate breast milk. Biosynthesis of a novel mixture of two major HMOs, lacto-N-fucopentaose I and 2'-fucosyllactose (LNFP-I/2'-FL), recently became possible. To support the safety of LNFP-I/2'-FL for use in infant formula and other foods, it was subject to a safety assessment comprising a bacterial reverse mutation test, an in vitro mammalian cell micronucleus test, and a 90-day oral gavage study in neonatal rats. In the 90-day study (the first HiMO study to include the new endocrine-sensitive endpoints described in the 2018 version of OECD Test Guideline 408), LNFP-I/2'-FL was administered by oral gavage to neonatal rats once daily (from Day 7 of age) for 90 consecutive days, at doses up to 5000 mg/kg bw/day, followed by a 4-week recovery period. Concurrent reference controls received 5000 mg/kg bw/day of the approved infant formula ingredient oligofructose. LNFP-I/2'-FL was nongenotoxic in vitro. The highest dose tested (5000 mg/kg bw/day) was established as the no-observed-adverse-effect level in the 90-day study, as there were no test article-related adverse effects on clinical observations, body weight, food consumption, clinical pathology, and organ weights nor any noteworthy macroscopic or microscopic findings. This supports the safety of LNFP-I/2'-FL for its intended uses in food.

Safety assessment of glutaminase from Aspergillus niger.

Glutaminase (glutamine aminohydrolase EC 3.5.1.2) is used in the production of food ingredients rich in l-glutamic acid that are added to finished foods for the purpose of enhancing or improving the savory flavor profile of food. The glutaminase enzyme preparation evaluated in these studies, designated as Sumizyme GT hereafter, is obtained by fermentation of Aspergillus niger strain GT147. The safety of Sumizyme GT was evaluated in a series of standard toxicological studies, including a 90-day oral toxicity study in rats, an in vitro bacterial reverse mutation assay, an in vitro mammalian chromosome aberration test, and an in vivo alkaline Comet assay. Sumizyme GT was not mutagenic or genotoxic, and administration of the enzyme by gavage at doses up to 2,570 mg total organic solids (TOS)/kg body weight (bw) per day for 90 days was without any systemic toxicity. The no-observed-adverse-effect level was concluded to be 2,570 mg TOS/kg bw per day, the highest dose tested. Considering that A. niger has an established history of safe use in the food industry and its safety in the production of food ingredients and food enzymes is well documented, the results of these studies provide further support of the safety of glutaminase from A. niger when used in food production.

Toxicological safety assessment of the human-identical milk oligosaccharide 3'-sialyllactose sodium salt.

Human breastmilk is a mixture of nutrients, hormones and bioactive molecules that are vital for infant growth and development. Infant formula (IF) lacks many of these compounds, most notably human milk oligosaccharides (HMOs), which are abundant in breastmilk but scarce in IF. Sialyllactoses, such as 3'-sialyllactose, constitute a large portion of the HMO fraction. To produce IF that matches breastmilk more closely, biosynthesized human-identical milk oligosaccharides (structurally identical to HMOs) such as 3'-sialyllactose sodium salt (3'-SL) are proposed for use in IF and foods for the general population. The safety assessment of 3'-SL comprised in vitro genotoxicity tests and a 90-day oral (gavage) toxicity study. This is the first 90-day study conducted with 3'-SL using neonatal rats (7 days old at the start of dosing-equivalent age to newborn human infants in terms of central nervous system and reproductive development), demonstrating the safety of 3'-SL for consumption by infants, the most sensitive age group. The neonatal rats received 3'-SL at doses up to 5,000 mg/kg body weight (BW)/day and reference controls received 5,000 mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in IF) for comparison with the high-dose 3'-SL group, followed by a 4-week recovery period. There was no evidence of genotoxicity in vitro. In the absence of any test item-related adverse effects in the 90-day study, the high dose (5,000 mg/kg BW/day) was established as the no-observed-adverse-effect level. This confirms the safety of 3'-SL for use in IF for infants, as well as in functional foods for the general population.

Risk Assessment Paradigm for Glutamate.

BACKGROUND: Re-evaluation of the use of glutamic acid and glutamate salts (referred to as glutamate hereafter) by the European Food Safety Authority (EFSA) proposed a group acceptable daily intake (ADI) of 30 mg/kg body weight (bw)/day. SUMMARY: This ADI is below the normal dietary intake, while even intake of free glutamate by breast-fed babies can be above this ADI. In addition, the pre-natal developmental toxicity study selected by EFSA, has never been used by regulatory authorities worldwide for the safety assessment of glutamate despite it being available for nearly 40 years. Also, the EFSA ignored that toxicokinetic data provide support for eliminating the use of an uncertainty factor for interspecies differences in kinetics. Key Messages: A 3-generation reproductive toxicity study in mice that includes extensive brain histopathology, provides a better point of departure showing no effects up to the highest dose tested of 6,000 mg/kg bw/day. Furthermore, kinetic data support use of a compound-specific uncertainty factor of 25 instead of 100. Thus, an ADI of at least 240 mg/kg bw/day would be indicated. In fact, there is no compelling evidence to indicate that the previous ADI of "not specified" warrants any change.

In vitro and in vivo assessment of the genotoxic activity of aloesin.

Aloesin is a chromone that is a component of Aloe spp. It may have potential as a functional food ingredient as it has been shown to likely have beneficial effects in persons in a pre-diabetic state or who have metabolic syndrome. In this study the safety of aloesin has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell cytogenetic, and mouse micronucleus tests. Aloesin did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at any of the tested dose levels up to 10,000 µg/plate. Similarly, aloesin did not increase the incidence of chromosome aberrations when incubated with Chinese hamster lung cells at any of the tested concentrations up to 10,000 µg/mL. In vivo, there was no effect of aloesin on the incidence of micronucleated erythrocytes following oral administration on two consecutive days at doses up to 5000 mg/kg body weight. There was no evidence of toxicity to bone marrow. The results of these studies demonstrate that aloesin is without genotoxic potential.

Toxicology review and risk assessment of resorcinol: thyroid effects.

Resorcinol administered at high doses to rodents can disrupt thyroid hormone synthesis and can produce goitrogenic effects. These effects were not seen in a 2-year bioassay at doses of up to 520 mg/kg/day. There are species-specific differences in synthesis, binding, and transport of thyroid hormone that complicate interpretation of goitrogenesis in rodents. Clinical case reports from patients undergoing resorcinol therapy for dermatological indications reveal thyroid side effects when copious amounts of resorcinol-containing ointments are applied to integrity-compromised skin for months to years. Effect levels were greater than 34 mg/kg/day. Occupational epidemiology studies provide no evidence that exposure to resorcinol at levels greater than found in the general environment causes thyroid dysfunction. Studies investigating the relationship between endemic goiter and exposure to "phenolics," including resorcinol, in drinking water do not fulfill accepted scientific criteria for establishing resorcinol as a cause of thyroid disease. Those reports neither quantify exposure levels nor demonstrate dose-response relationships or rule out confounding by the multiple other chemicals present in water supplies, by bacterial contamination of water, or by nutritional factors. A risk assessment comparing potential worst-case exposures to resorcinol through its use in dermatological preparations supports the conclusion that under real-world conditions, human exposures to resorcinol are not expected to cause adverse effects on thyroid function.