title: The challenge of using read-across within the EU REACH regulatory framework; how much uncertainty is too much? Dipropylene glycol methyl ether acetate, an exemplary case study.
abstract: The use of read-across of data within a group of structurally similar substances potentially allows one to characterise the hazards of a substance without resorting to additional animal studies. However the use of read-across is not without challenges, particularly when used to address the needs of a regulatory programme such as the EU REACH regulation. This paper presents a case study where a previously accepted read-across approach was used to address several data gaps in a REACH registration dossier but was subsequently rejected in part by the European Chemicals Agency (ECHA), resulting in the requirement to perform a developmental toxicity study in rodents. Using this case study, this paper illustrates some of the practical challenges faced when making use of read-across, particularly with respect to addressing the uncertainty associated with the use of read-across; showcasing the scientific justification and highlighting some of the potential implications/opportunities for future cases.
authors.affiliation: Toxicology & Environmental Research and Consulting (TERC), Dow Europe GmbH, Bachtobelstrasse 3, CH-8810 Horgen, Switzerland. Electronic address: nball@dow.com.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ball
authors.affiliation: Toxicology & Environmental Research and Consulting (TERC), The Dow Chemical Company, 1803 Bldg, Washington Street, Midland, MI 48674, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Toxicology & Environmental Research and Consulting (TERC), The Dow Chemical Company, 1803 Bldg, Washington Street, Midland, MI 48674, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Budinsky
authors.affiliation: Toxicology & Environmental Research and Consulting (TERC), The Dow Chemical Company, 1803 Bldg, Washington Street, Midland, MI 48674, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Klapacz
authors.affiliation: Summit Toxicology, 165 Valley Road, Lyons, CO 80540, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Hays
authors.affiliation: Summit Toxicology, 29449 Pike Drive Orange Village, OH 44022, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kirman
authors.affiliation: DuPont Haskell Global Centers for Health and Environmental Sciences, 1090 Elkton Road, Newark, DE 19711, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Patlewicz
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D005062:European Union; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D011409:Propylene Glycols / Q000633:toxicity*; D018570:Risk Assessment / Q000331:legislation & jurisprudence / Q000379:methods*; D012377:Rodentia; D035501:Uncertainty
chemical_list: D015386:Hazardous Substances; D011409:Propylene Glycols; C547918:dipropylene glycol monomethyl ether acetate
keywords: CAS No. 88917-22-0; Dipropylene glycol methyl ether acetate (DPMA); REACH; Read-across; Uncertainty