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.

Abstract  The category contains four structurally related propylene glycol ethers: - Propylene Glycol n-Butyl Ether (PnB, 5131-66-8, major (“alpha”) isomer, 29387-86-8 isomeric mixture) - Dipropylene Glycol n-Butyl Ether (DPnB, 29911-28-2 major isomer or 35884-42-5 isomeric mixture)) - Dipropylene Glycol Methyl Ether Acetate (DPMA, 88917-22-0 isomeric mixture) - Tripropylene Glycol Methyl Ether (TPM, 20324-33-8 one of the isomers and 25498-49-1 isomeric mixture) The alpha (secondary alcohol) form is kinetically favored during synthesis. PnB is available as the isomeric mixture in which the alpha isomer is the predominant isomer (ca. 95%. DPnB, DPMA and TPM are commercially produced as mixtures of isomeric components in which the internal ether linkages may be adjacent to either primary or secondary carbon atoms. Thus, for DPMA and DPnB the commercially produced products may contain up to 4 such isomers. In the case of TPM, the commercially produced product may contain up to 8 such isomers. Data for these propylene glycol ethers are supplemented with data from three propylene glycol ethers that are closely related to the category members in molecular structure, physicochemical properties and toxicity and thus extend the category. These compounds are: - Propylene Glycol Methyl Ether (PM; CAS No. 107-98-2) - Propylene Glycol Methyl Ether Acetate (PMA; CAS No. 108-65-6) - Dipropylene Glycol Methyl Ether (DPM; CAS No. 34590-94-8 isomeric mixture and 20324-32-7 major isomer) PM and PMA were reviewed at SIAM 11 and DPM was reviewed at SIAM 12. All were assigned as low priority for further work.

Abstract  OBJECTIVE: The objective of this study is to review the reported toxicity of reed diffuser fragrance liquid which, in addition to essential oils, commonly contains glycol ethers but other ingredients and/or alternatives are 3-methoxy-3-methyl-1-butanol, petroleum distillates, ethanol and isopropanol.

METHODS: We analysed retrospectively enquiries to the United Kingdom National Poisons Information Service between 1 January 2010 and 31 December 2014.

RESULTS: 754 patients were exposed to reed diffusers; the majority (n = 712) were children < 5 years. Ingestion was the most common route of exposure (706 of 754 patients) and involved the liquid alone (n = 570), water beads alone (n = 84), sucking on the reeds (n = 31) or ingesting the liquid and water beads (n = 21). The reported amount of fragrance liquid ingested was known in only 76 of 591 cases (12.9%), with a median (IQR) volume of 20.0 (IQR = 10-40) mL. The WHO/IPCS/EC/EAPCCT Poisoning Severity Score (PSS) was known in 702 of 706 sole ingestions: in 574 (81.3%), the PSS was 0 (asymptomatic); in 117 (16.6%) patients, the PSS was 1 (minor toxicity); in 11 (1.6%), the PSS was 2 (moderate toxicity); there were no patients with features graded PSS 3 (severe toxicity). Significantly (p = 0.008) more patients became symptomatic (PSS 1 and PSS 2) following the ingestion of a reed diffuser containing 3-methoxy-3-methyl-1-butanol than propylene glycol monobutyl ether, though there was no significant difference when compared with those containing dipropylene glycol monomethyl ether (p = 0.181). The most common features following ingestion of fragrance liquid were nausea and vomiting (n = 53), coughing (n = 17) and CNS depression (n = 9). Seven patients suffered eye exposure alone: two developed eye pain and four conjunctivitis. Dermal exposure alone was reported in six patients, two of whom developed skin irritation.

CONCLUSIONS: The majority of patients in our study developed no features or only minor symptoms following ingestion of reed diffuser fragrance liquid.

Abstract  Silica-based chemical gel for the decontamination of nuclear facilities was prepared using fumed silica as a viscosifier, a 0.5 M Ce (IV) solution dissolved in concentrated nitric acid as a chemical decontamination agent and tripropylene glycol butyl ether (TPGBE) as a coviscosifier. A new effective strategy for the preparation of the chemical gel was investigated by introducing the alkyl alcohols as organic solvents to effectively dissolve the coviscosifier. Using the mixture solution of the coviscosifier and alkyl alcohol was more effective in the control of viscosity than that of only coviscosifier in the gel. Here, alkyl alcohols play a key role as an effective dissolution solvent for the covicosifier in the preparation of the chemical gel, resulting in a reduction of the amount of covicosifier and gel time compared with that of the chemical gel prepared without alkyl alcohols. It was considered that the alkyl alcohols contributed to the effective dissolution of the coviscosifier as well as homogeneous mixing in the formation of the gel, while the coviscosifier in an aqueous media of the chemical decontaminant solution showed a lower solubility. The decontamination efficiency of the chemical gels prepared in this work using a multi-channel analyzer showed a high decontamination efficiency of over ca. 94 % and ca. 92 % for Co-60 and Cs-137 contaminated on the surface of stainless steel 304, respectively.