Identifying Greener and Safer Plasticizers: A 4-Step Approach.

Area of Science:

• Environmental Chemistry
• Toxicology
• Chemical Engineering

Background:

• Endocrine disrupting chemicals (EDCs) like di(2-ethylhexyl) phthalate (DEHP) pose significant health and economic risks.
• The development of DEHP alternatives lacks mandatory safety assessments, potentially leading to replacements with similar or greater toxicity.
• There is a growing consensus among scientists, regulators, and industry for proactive strategies in designing safer chemical substitutes.

Purpose of the Study:

• To propose and illustrate a systematic four-step approach for the design, characterization, and toxicological evaluation of responsible chemical alternatives.
• To identify and validate safer replacements for DEHP, focusing on environmental and toxicological profiles.

Main Methods:

• Chemical design incorporating innovative structures and environmental considerations.
• High-throughput in vitro and selective ex vivo assays for initial safety screening.
• In vivo acute toxicity studies to exclude overt toxicity.
• In utero and lactational exposure studies to compare candidate alternatives with DEHP, assessing key toxicological endpoints.

Main Results:

• Two alternative chemicals with desirable plasticizing properties, enhanced biodegradability, and reduced leaching compared to DEHP were identified.
• The selected alternatives demonstrated no apparent toxicity in in vivo studies.
• The proposed four-step approach proved effective in the proactive identification of DEHP replacements.

Conclusions:

• A structured, four-step methodology enables the development of safer chemical alternatives.
• This proactive approach successfully identified DEHP replacements with improved environmental and toxicological profiles.
• The strategy facilitates responsible chemical design, mitigating risks associated with endocrine disruptors.