Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

The following remarks on toxicokinetics are based on the physico-chemical properties of the substance and on toxicological data. Experimental studies on toxicokinetics were not performed.

The substance is a colourless liquid (Neuland, 2012) with a vapour pressure under normal ambient conditions of 0.21 Pa (2.1 x 10-3 mbar) at 20 °C (Fonseca, 2012). From these data vapour inhalation might be a route of exposure whereas the vapour pressure is characterized by DEG which is contained in the multi constituent substance up to 57 %. However systemic availability of Ester PSA + DEG after inhalative exposure is not proven due to the NOAEL (= 1000 mg/kg = limit dose) in the subacute oral study (Popp, 2013) whereas local irritating effect is expected for Ester PSA + DEG from the pH value of 2 and the positive responses in the in vitro test systems for ocular irritation/damage if the intire multi constituent substance reaches the lung. 

Although the physico-chemical characteristics of the substance (soluble in demineralized water in each ratio to clear homogenous solutions(10000 mg/L) at 20°C, Neuland, 2012), log Pow of 1 at 25 °C (Garcia-Sanchez, 2013)) and a molecular mass of 248 g/mol (Prüm, 2012) suggest intestinal absorption after oral intake the data on acute oral toxicity in rats (LD50 cut off> 5000 mg/kg bw, Gillissen, 2012) and the results of a subacute oral study in rats (Popp, 2013) with a NOAEL of 1000 mg/kg bw for rats provide no evidence for that assumption.

Due to the high water solubility and a molecular mass of 248 g/mol dermal uptake of Ester PSA + DEG is likely to be low, even if a log Pow of 1 at 25°C favour dermal absorption particularly if water solubility is high. The study results on acute dermal toxicity (rat, LD50 > 2000 mg/kg bw; Gillissen, 2012) skin irritation (no systemic effects, Leuschner, 2012) and skin sensitization (LLNA, negative; Vohr 2012) confirmed both assumptions because lack of systemic toxicity may reflect that there is no dermal uptake or Ester PSA + DEG has no effect.

Deducing from the repeated dose toxicity study, where no systemic toxicity was reported, no potential for accumulation is to be expected for the substance.

Based on the results of in vitro genotoxicity tests (negative with and without metabolic activation in Ames test, Nern, 2012; HPRT test, Wollny, 2012; Micronucleus test, Nern, 2012) it is concluded that DNA-reactive metabolites of ester PSA + DEG will most probably not be generated in mammals in the course of hepatic biotransformation if bioavailability is given. 

 

Categories Display