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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: expert statement
Adequacy of study:
key study
Study period:
2015
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Theoretical assessment taking all currrently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. Since this is a theoretical assessment, the maximum Klimisch value is 2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Objective of study:
other: oral, dermal and inhalation absorption assessment based on all available data
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Reaction products of pentaerythritol, propoxylated and 1-chloro-2,3-epoxypropane with hydrogen sulfide
EC Number:
701-196-7
Cas Number:
72244-98-5
Molecular formula:
not applicable
IUPAC Name:
Reaction products of pentaerythritol, propoxylated and 1-chloro-2,3-epoxypropane with hydrogen sulfide

Results and discussion

Main ADME results
Type:
absorption
Results:
For risk assessment purposes, 100% is used for oral, dermal and inhalation absorption

Any other information on results incl. tables

A substance can enter the body via the gastrointestinal tract, the lungs, or the skin, depending on the exposure route.

After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract. GPM-800 dissolves in water (62 g/L (at 20°C), therefore it is expected to readily dissolve into the gastrointestinal fluids. In principle, this would allow passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water). GPM-800 is a  polymeric mercaptan with a considerable size range (appr. 490-1474 g/mol). As absorption is estimated to be still possible via this route for molecules with a molecular weight below 1000, some uptake via passive diffusion is expected for GPM-800. Furthermore, the substance dissolves in n-octanol, which results in a moderate partition coefficient (log Pow > 1.2 (at 20°C)). This lipophilic characteristic favors absorption by passive diffusion. The hydrolysis rate is slow (t1/2  > 1 year at 25°C at pH 4, 7 and 9) and is not further expected to influence the uptake. In conclusion, its solubility in water, its moderate partition coefficient and its molecular size will allow oral absorption. For risk assessment purposes oral absorption of GPM-800 is therefore set at 100% . The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor. Once absorbed, wide distribution of GPM-800 throughout the body is expected based on its water solubility and its molecular weight range. As GPM-800 dissolves both in water and in n-octanol, it is expected not to have a special preference for fatty tissues. GPM-800 is expected to be excreted via urine. Based on these facts, GPM-800 is not expected to bio-accumulate significantly in the body upon exposure.

GPM-800 is a liquid with low volatility, as reflected in a low vapour pressure (0.16 Pa at 20°C) and absence of a boiling point (substance decomposes at ≥320°C). This implies that exposure via inhalation of vapour of GPM-800 is not likely to occur. However, liquid aerosols can be formed, which can be inhaled. Once GPM-800 reaches the lung tissue, it will readily dissolve in the mucus lining of the respiratory tract. The moderate lipohilicity allows the substance to cross the alveolar and capillary membranes by passive diffusion and be absorbed. Based on the above data, for risk assessment purposes the inhalation absorption of GPM-800 is set at 100%.

In general, liquids such as GPM-800 are taken up more readily than dry particulates. In order to cross the skin, a compound must first penetrate into the stratum corneum (non-viable layer of corneocytes forming a complex lipid membrane) and subsequently reaches the viable epidermis, the dermis and the vascular network. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to penetration by highly lipophilic compounds.  The combined characteristics of moderate water solubility and moderate lipophilicity of GPM-800 enables the substance to cross both barriers. Therefore dermal absorption is likely to be high. GPM-800 is slightly surface active, with a surface tension of 29.9 mN/m (at 20°C, at 250 mg/L). However at this value, this characteristic is not expected to be of major influence on the uptake (only surfactants with a surface tension < 10 mN/m are expected to greatly enhance dermal uptake). On the other hand, the molecular size of GPM-800 (representative MW appr. 800 g/mole) is expected to hamper dermal absorption as it may be too large for uptake across biomembranes. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. Both the molecular weight of GPM-800 (approx. 490-1474 g/mol) and the moderate partition coefficient do not meet the criteria for limited dermal absorption. Therefore, for risk assessment purposes dermal absorption is set at 100%.

Applicant's summary and conclusion

Conclusions:
For risk assessment purposes the oral, dermal and inhalation absorption of GPM-800 is each set at 100%.