Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 214-881-6 | CAS number: 1205-17-0
Following incubation of epidermal membranes with the radiolabeled test item, only 67% of the applied dose was accounted for by 48 h. At 24 and 48 h, 42% and 50%, respectively, of the applied close was recovered in the fluid retrieved from the receptor chambers. Distribution of remaining radiolabel in surface wipes, tape strips, remaining epidermis and the donor chamber surface accounted for an additional 17%. The chemical nature of the absorbed radiolabel was not characterized (i.e. parent test item or metabolites). Evaporative loss, estimated from direct application to PTFE sheets, was approximately 8% and 19% of the applied dose at 24 and 48 h, respectively.
An in vitro dermal absorption studies according to the FDA/AAPS guidelines (Skelly et al., 1987) was performed with full thickness human skin samples. Twenty µL of a 1% solution in ethanol of radiolabeled test item (0.2 mCi benzyl-14C. specific activity of 57.26 mCi/mmol; radiochemical purity of 99.14%) was applied to the surface of the membrane. Receptor chambers were continuously agitated by submersible magnetic stirrers and maintained at 37 °C throughout the experiment. The skin surface temperature was maintained at 32 °C. Samples of the receptor fluid (50% ethanol/water) were harvested from the receptor chamber at 2, 8, 24, 36 and 48 h and analysed by liquid scintillation chromatography. Post-incubation epidermal membranes were wiped with a cotton bud, and then tape stripped 10 times using adhesive tape. Total radioactivity was accounted for by extruding and counting test item equivalents associated with membrane wipes, tape strips, digested remaining skin, and donor chambers. To assess evaporative loss, 20 µL of a 1% test item solution was applied to PTFC sheets mounted in diffusion cells (at 32 °C surface temperature). These sheets were then placed in chambers for 24 or 48 h. The PTFE sheet was then removed and washed twice with methanol (10 mL then 5 mL). The donor chamber was washed with 10 ml methanol. A sample of each wash solution was submitted to analysis by LSC which allowed the total remaining radiolabel at each timepoint to be determined. Radiolabel that was unaccounted for was considered to be associated with evaporative loss.
In a combined OECD Guideline 422 repeat dose study (Takano, 2016) a NOEL of 100 mg/kg/day was obtained, indicating that oral uptake of the substance occurs.
In an in vitro study using human skin 50 % of the applied dose were absorbed, indicating that the substance has a high skin penetration potential.
The substance has a molecular weight < 500, which is favourable for uptake. The substance also has a logP that is favourable for absorption (logP 2.4).
An acute oral study (Mallory, 1985) indicates that uptake does occur, with some systemic signs being noted at 1600, 2000 and 2500 mg/kg and death occurring at 3200 and 5000 mg/kg. In a combined repeat dose study (Takano, 2016) a NOEL of 100 mg/kg/day was obtained, again indicating that oral uptake does occur. However, very little on the quantitative value of oral absorption can be inferred from these studies.
In the absence of quantitive data, but in light of the high dermal absorption, oral absorption is set to 100% for the purposes of risk assessment.
In an in vitro study using human skin 50% of the applied dose were absorbed. Therefore, 50% absorption following dermal exposure is assumed for the purposes of risk assessment.
In the absence of quantitative information, complete absorption (100%) following inhalation is assumed for the purposes of risk assessment.
It can be expected that once absorbed the substance will be widely distributed throughout the body.
There is no metabolism data available for this substance. Conjugation is likely to occur, which will increase the water solubility and make the substance easier to excrete. There is considered to be no potentential for bioaccumulation.
Although there is no elimination data available for this substance, compounds with a molecular weight < 300 tend to be excreted in the urine.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again