Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
Justification for type of information:
The testing of acute dermal toxicity of L-Asparagine is scientifically not justified based on its physicochemical properties. Although L-Asparagine exhibits a low molecular weight (132.119 g/mol) which favours dermal uptake, it exhibits also a very low log Kow (-3.82) and a high water solubility (25.1 g/L), thus, according to ECHA guidance on information requirements Chapter R.7c the substance is not considered to penetrate the stratum corneum due to its hydrophilicity.
Furthermore, testing of acute dermal toxicity of the substance is not justified due to the available data on acute oral toxicity. Retrospective data analyses undertaken by Creton et al. (2010) and Seidle et al. (2010) evaluate the value of regulatory requirements prescribing multiroute testing for acute systemic toxicity. These analyses have examined the concordance among regulatory classifications for acute oral, dermal, and/ or inhalation toxicity for ~500 agrochemical and biocidal active substances and nearly 2000 industrial chemicals. The findings from these two independent reviews have revealed that acute dermal studies of pure substances do not add value above and beyond oral data for hazard classification of pesticides, biocides, or chemicals. According to the COMMISSION REGULATION (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity, recent “scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.” The oral LD50 was determined to be > 2000 mg/kg bw. Thus, no toxicity via the dermal route is to be expected.

References: Creton S. et al.: Acute toxicity testing of chemicals—Opportunities to avoid redundant testing and use alternative approaches, Critical Reviews in Toxicology, 2010; 40(1): 50–83 Seidle T. et al.: Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing, TOXICOLOGICAL SCIENCES 116(2), 382–396 (2010).

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion