Informed substitution of hazardous chemicals through the lens of California's Safer Consumer Products Alternatives Analysis: Best practices, challenges, and opportunities.

California adopted the Safer Consumer Products (SCP) regulations in 2013, which mandate that companies that manufacture specific products containing designated chemicals of concern complete an Alternatives Analysis. Alternatives Analysis is a process to avoid regrettable substitution by identifying, comparing, and selecting safer alternatives based on technical functions, hazards, exposure pathways, life-cycle multimedia impacts, and economic impacts. The SCP Alternatives Analysis builds upon and expands existing frameworks for alternatives assessments (AAs). The aim of this study was to identify practices from AA that facilitate the robust assessment of alternatives and that align with SCP requirements and identify gaps in the practice. We evaluated completed AAs for methods regarding transparency and careful documentation of information sources, data gaps, uncertainty, criteria, and justification for decision-making. The AAs in this review demonstrate some of the challenges in the field. Most AAs have a constrained scope and only consider chemical substitutes rather than a broad array of functional alternatives. Their scopes were also limited in the hazard endpoints that were evaluated. This was most noted with ecotoxicity endpoints, which were generally confined to aquatic toxicity. The majority of AAs do not explicitly explain their decision-making methods or adequately discuss tradeoffs across the adverse impacts. The AAs also lack the analysis in the exposure, life-cycle impacts, and economic impacts that are required in the SCP Alternatives Analysis process. Further, we recommend strategies and research opportunities to address these challenges and strengthen the practice of AAs. Integr Environ Assess Manag 2022;18:1007-1019. © 2021 SETAC.

prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

The zinc finger domain transcription factor prdm1a plays an integral role in the development of the neural plate border cell fates, including neural crest cells and Rohon-Beard (RB) sensory neurons. However, the mechanisms underlying prdm1a function in cell fate specification is unknown. Here, we test more directly how prdm1a functions in this cell fate decision. Rather than affecting cell death or proliferation at the neural plate border, prdm1a acts explicitly on cell fate specification by counteracting olig4 expression in the neighboring interneuron domain. olig4 expression is expanded in prdm1a mutants and olig4 knockdown can rescue the reduced or abrogated neural crest and RB neuron phenotype in prdm1a mutants, suggesting a permissive role for prdm1a in neural plate border-derived cell fates. In addition, prdm1a expression is upregulated in the absence of Notch function, and inhibiting Notch signaling fails to rescue prdm1a mutants. This suggests that prdm1a functions downstream of Notch in the regulation of cell fate at the neural plate border and that Notch regulates the total number of progenitor cells at the neural plate border.

Regulation of latent sensory hair cell precursors by glia in the zebrafish lateral line.

The lateral line is a placodally derived mechanosensory organ in anamniotes that detects the movement of water. In zebrafish embryos, a migrating primordium deposits seven to nine clusters of sensory hair cells, or neuromasts, at intervals along the trunk. Postembryonically, neuromasts continue to be added. We show that some secondary neuromasts arise from a pool of latent precursors that are deposited by the primordium between primary neuromasts. Interneuromast cells lie adjacent to the lateral line nerve and associated glia. These cells remain quiescent while they are juxtaposed with the glia; however, when they move away from the nerve they increase proliferation and form neuromasts. If glia are manually removed or genetically ablated by mutations in cls/sox10, hypersensitive (hps), or rowgain (rog), neuromasts precociously differentiate. Transplantation of wt glia into mutants rescues the appropriate temporal differentiation of interneuromast cells. Our studies reveal a role for glia in regulating sensory hair cell precursors.