Registration Dossier
Registration Dossier
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EC number: 412-260-6 | CAS number: 52658-19-2 MONO 442
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 100
- Absorption rate - inhalation (%):
- 100
Additional information
Oral:
In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration (1). Based on the moderate water solubility (224 mg/L) and the lipophilic character of the main constituent (Log Kow 2.7), the substance has the potential to be absorbed by passive diffusion. Further, the relatively low molecular weight (442.5) is favourable for absorption. However, ionization of the substance will possibly impair the uptake since compounds need to pass the lipid membranes in the gastrointestinal wall (1). Overall, absorption of the substance from the gastrointestinal tract is expected to be likely, which is also confirmed by the results from the repeated dose studies in which systemic toxicity was present. Therefore, in absence of toxicokinetic data, for risk assessment purposes the oral absorption of the substance is set at 50%.
Once absorbed, distribution of the substance throughout the body is expected based on its relatively low molecular weight and moderate water solubility. Based on its relatively lipophilic character, intracellular concentration is expected to be higher than extracellular concentration. The absorbed substance might undergo conjugation (2). The conjugates will either be excreted via the bile (high molecular weight compounds) or the urine (low molecular weight compounds).
Inhalation:
The high boiling point (>250°C) and low vapour pressure (0.7 Pa) indicate that it is not likely that the substance will reach the nasopharyngeal region or subsequently the tracheobronchial or pulmonary region. If the substance reaches the tracheobronchial region, absorption through aqueous pores will be limited, taking the molecular weight of >200 into account. However, its moderate lipophilic character is favourable for crossing the alveolar and capillary membranes and the moderate water solubility of the substance is favourable for dissolution of the substance in the mucus lining of the respiratory tract. If the substance is inhaled, significant absorption of the substance is to be expected. Therefore, in absence of toxicokinetic data, for risk assessment purposes the inhalation absorption of the substance is set at 100%.
Dermal:
The substance being a liquid has the potential to partition from the stratum corneum into the epidermis, which is also enhanced by the moderate water solubility. Further, the moderate lipophilic character of the major constituent (log Kow 2.7) indicates that the transfer between the stratum corneum and the epidermis will be likely. Based on the molecular weight and the log Kow, the criteria for 10% dermal absorption as given in the TGD (3) (MW > 500 and log Kow < -1 or> 4) are not met, and hence a default dermal absorption of 100% is proposed for risk assessment purposes. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.
Based on the present available data, no additional conclusions can be drawn on the metabolism and excretion of the substance after dermal and inhalatory absorption.
References:
1. Martinez MN, Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol 2002; 42: 620-43.
2. Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, November 2014.
3. A. Parkinson. In: Casarett and Doul/'s Toxicology, The basic science of poisons. Sixth edition. Ed. G.D. Klaassen. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, 2001.
Bioaccumulation potential: The n-octanol-water partition co-efficient (log Kow) of the substance is 2.7. Therefore,
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