Pediatric Toxicology: An Updated Review.

Pediatricians should be familiar with principles of medical toxicology given that intentional and unintentional ingestions are commonly encountered in different medical settings. Most exploratory ingestions are well tolerated and do not cause significant health effects, but a few noteworthy exceptions can lead to serious illness and death. This article reviews common medications and household products likely to cause significant toxicity in pediatric patients, even in small, exploratory ingestions. Increasing cannabis exposures among children and adolescents are also reviewed. Additionally, indications for gastric decontamination with activated charcoal are reviewed. Finally, poisoning prevention strategies are reviewed. [Pediatr Ann. 2023;52(4):e139-e145.].

Rising incidence and high mortality in intentional sodium nitrite exposures reported to US poison centers.

INTRODUCTION: Sodium nitrite is an oxidizing agent capable of producing profound methemoglobinemia. Large quantities of sodium nitrite can be purchased online, and recent literature has identified several cases of intentional self-poisoning, including multiple cases of mortality. This has raised concern that intentional sodium nitrite poisoning and resultant severe methemoglobinemia may be increasing in incidence and could represent a substantial public health threat. MATERIALS AND METHODS: This study used data obtained from the National Poison Data System (NPDS) to evaluate the incidence and mortality rate of intentional sodium nitrite poisoning of suicidal intent reported to US poison centers over a five-year period. Patient demographics, exposure characteristics, treatments administered, and patient outcomes were analyzed. Temporal patterns in exposure were also investigated. RESULTS: Forty-seven cases were identified in the NPDS database, of which three were excluded due to lack of outcome data. Median patient age was 23 years, 52% of patients were female and 86% of exposures occurred at the patient's residence. Serious outcomes were observed in 84% of cases, 77% of patients included were treated with methylene blue and 30% of patients died. No intentional sodium nitrite exposures were reported in the first two years studied, but we observed an increase in the incidence of exposures reported through the remainder of the investigation period. DISCUSSION/CONCLUSIONS: The incidence of intentional self-poisoning with sodium nitrite has been increasing since 2017. Many of these exposures result in toxicity requiring antidotal therapy, and a high mortality rate was observed. Recent literature indicates that this trend may be the result of ready access to this poison through online vendors combined with recommendations shared in online communities that sodium nitrite be used as an effective method of suicide. Further study is needed to better characterize this phenomenon and develop public health interventions to prevent future morbidity and mortality.

Molecular and organismal changes in offspring of male mice treated with chemical stressors.

Both gene methylation changes and genetic instability have been noted in offspring of male rodents exposed to radiation or chemicals, but few specific gene targets have been established. Previously, we identified the gene for ribosomal RNA, rDNA, as showing methylation change in sperm of mice treated with the preconceptional carcinogen, chromium(III) chloride. rDNA is a critical cell growth regulator. Here, we investigated the effects of paternal treatments on rDNA in offspring tissue. A total of 93 litters and 758 offspring were obtained, permitting rigorous mixed-effects models statistical analysis of the results. We show that the offspring of male mice treated with Cr(III) presented increased methylation in a promoter sequence of the rDNA gene, specifically in lung. Furthermore polymorphic variants of the multi-copy rDNA genes displayed altered frequencies indicative of structural changes, as a function of both tissue type and paternal treatments. Organismal effects also occurred: some groups of offspring of male mice treated with either Cr(III) or its vehicle, acidic saline, compared with those of untreated mice, had altered average body and liver weights and levels of serum glucose and leptin. Males treated directly with Cr(III) or acidic saline presented serum hormone changes consistent with a stress response. These results establish for the first time epigenetic and genetic instability effects in a gene of central physiological importance, in offspring of male mice exposed preconceptionally to chemicals, possibly related to a stress response in these males.

Ontogeny-driven rDNA rearrangement, methylation, and transcription, and paternal influence.

Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and its subsequent epigenetic modifications may also take place during mammalian ontogeny, a process undergoing finely orchestrated cell division and differentiation. We tested this hypothesis by comparing single nucleotide polymorphism-defined haplotype frequencies and DNA methylation of the rDNA multicopy gene between two mouse ontogenic stages and among three adult tissues of individual mice. Possible influences to the genetic and epigenetic dynamics by paternal exposures were also examined for Cr(III) and acid saline extrinsic factors. Variables derived from litters, individuals, and duplicate assays in large mouse populations were examined using linear mixed-effects model. We report here that active rDNA rearrangement, represented by changes of haplotype frequencies, arises during ontogenic progression from day 8 embryos to 6-week adult mice as well as in different tissue lineages and is modifiable by paternal exposures. The rDNA methylation levels were also altered in concordance with this ontogenic progression and were associated with rDNA haplotypes. Sperm showed highest level of methylation, followed by lungs and livers, and preferentially selected haplotypes that are positively associated with methylation. Livers, maintaining lower levels of rDNA methylation compared with lungs, expressed more rRNA transcript. In vitro transcription demonstrated haplotype-dependent rRNA expression. Thus, the genome is also dynamic during mammalian ontogeny and its rearrangement may trigger epigenetic changes and subsequent transcriptional controls, that are further influenced by paternal exposures.