Human, skin sensitisation human Analogue 1 Not sensitising – maximisation test (HMT) and diagnostic patch test Rat, repeat dose oral toxicity 90 days Analogue 4 NOAEL = 300 mg/kg bw – Genotoxicity -bacterial reverse mutation Analogue 5 Non-mutagenic Genotoxicity in vivo mouse micronucleus Analogue 1 Not genotoxic – test The results from the data submitted for the new chemical assessment (NICNAS, 2007) are summarised in the following table and text. The robust study summaries of these data are provided in Appendix A.2. Studies available for the new chemical assessment Endpoint Test substance Result and assessment conclusion Rat, acute oral Analogue 1 LD50 > 2000 mg/kg bw, low toxicity Rat, acute dermal Notified chemical LD50 > 2000 mg/kg bw, low toxicity Rabbit, skin irritation Analogue 1 Slightly irritating Rabbit, eye irritation (undiluted test Analogue 1 Severely irritating substance) Rabbit, eye irritation (undiluted test Analogue 1 Slightly irritating substance, low volume procedure) Rabbit, eye irritation (5% diluted test Analogue 1 Not irritating substance) Guinea pig, skin sensitisation guinea Analogue 1 Inconclusive – pig maximisation test (GPMT) Rat, repeat dose oral toxicity 28 Notified chemical NOAEL = 1000 mg/kg bw – days Genotoxicity -bacterial reverse Analogue 2 Non-mutagenic mutation Genotoxicity in vitro mammalian Notified chemical Non-genotoxic – chromosome aberration test The new chemical assessment (NICNAS, 2007) and the HERA report (2009) noted that the test substances may contain the additive, 2-propanol (CAS no. 67-63-0), which is classified as an eye and respiratory irritant (Safe Work Australia, 2018). Therefore, the toxicity of the analogue could be biased by the toxicity of this impurity. Toxicokinetics, metabolism and distribution No toxicokinetic data were provided for the secondary notification. The original new chemical assessment stated that based on the physical and chemical properties, the absorption of the chemical via the various routes is expected to be as follows:
Human, skin sensitisation – human maximisation test (HMT) and diagnostic patch test Analogue 1 Not sensitising Rat, repeat dose oral toxicity – 90 days Analogue 4 NOAEL = 300 mg/kg bw Genotoxicity -bacterial reverse mutation Analogue 5 Non-mutagenic Genotoxicity – in vivo mouse micronucleus test Analogue 1 Not genotoxic The results from the data submitted for the new chemical assessment (NICNAS, 2007) are summarised in the following table and text. The robust study summaries of these data are provided in Appendix A.2. Studies available for the new chemical assessment Endpoint Test substance Result and assessment conclusion Rat, acute oral Analogue 1 LD50 > 2000 mg/kg bw, low toxicity Rat, acute dermal Notified chemical LD50 > 2000 mg/kg bw, low toxicity Rabbit, skin irritation Analogue 1 Slightly irritating Rabbit, eye irritation (undiluted test substance) Analogue 1 Severely irritating Rabbit, eye irritation (undiluted test substance, low volume procedure) Analogue 1 Slightly irritating Rabbit, eye irritation (5% diluted test substance) Analogue 1 Not irritating Guinea pig, skin sensitisation – guinea pig maximisation test (GPMT) Analogue 1 Inconclusive Rat, repeat dose oral toxicity – 28 days Notified chemical NOAEL = 1000 mg/kg bw Genotoxicity -bacterial reverse mutation Analogue 2 Non-mutagenic Genotoxicity – in vitro mammalian chromosome aberration test Notified chemical Non-genotoxic The new chemical assessment (NICNAS, 2007) and the HERA report (2009) noted that the test substances may contain the additive, 2-propanol (CAS no. 67-63-0), which is classified as an eye and respiratory irritant (Safe Work Australia, 2018). Therefore, the toxicity of the analogue could be biased by the toxicity of this impurity. Toxicokinetics, metabolism and distribution No toxicokinetic data were provided for the secondary notification. The original new chemical assessment stated that based on the physical and chemical properties, the absorption of the chemical via the various routes is expected to be as follows:
Ethanaminium,-2-hydroxy-N,N-bis2-hydroxyethyl-N-methyl-,-esters-with-C16-18-and-C18-unsatd.-fatty-acids,-Me-sulfates-saltsSTD-1258S-Final-SNA-report-Oct-2018.DOCX