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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2022
Report date:
2022
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate
EC Number:
220-482-8
EC Name:
Diethyl bis(2-hydroxyethyl)aminomethylphosphonate
Cas Number:
2781-11-5
Molecular formula:
C9H22NO5P
IUPAC Name:
diethyl {[bis(2-hydroxyethyl)amino]methyl}phosphonate
Test material form:
liquid

Results and discussion

Applicant's summary and conclusion

Executive summary:

There are no experimental toxicokinetic data available for the substance and this statement is based on available data as physico-chemical data and toxicological data. This assumption was conducted based on the REACH ECHA “Guidance on information requirements and chemical safety assessment chapter R.7c” of the ECHA guidance document (Version 3.0, June 2017).


 


Available physico-chemical information taken into account:


Physical state:


The substance is an organic, brown to amber colored liquid at ambient temperature.


 


Structure:


diethyl bis(2-hydroxyethyl)aminomethylphosphonate


 


Molecular mass:


C9H22NO5P; 255 g/mol


 


Water solubility:


>1000 g/L at 25 °C


 


Log Pow:


log Pow = -1.94 (QSAR calculation)


 


Vapor pressure:


0.0000122 Pa at 25 °C (QSAR calculation)


 


General considerations:


In general, log Kow values between 1 and 4 are favourable for absorption regarding oral/GI absorption, respiratory absorption and dermal absorption.


Based on the low log Pow of -1.94 absorption is likely to be limited and low. No information of metabolic transformation is available.


 


Estimation of oral absorption:


In two early acute oral toxicity studies in rats no mortality were observed at the highest doses tested (5000 and 17460 mg/kg).


Subchronic oral toxicity was determined using 22 rats/sex/group treated by gavage daily for three months at doses of 0, 20, 100 or 500 mg/kg. Test item treatment resulted in measurable effects upon rat liver and kidney. These effects were indicative of an adaptive rather than a toxic response (NOAEL = 500 mg/kg; highest dose tested). No evidence of a treatment-related alteration was found in rats given the lowest dose (NOEL = 20 mg/kg).


In the in vivo mammalian alkaline comet assay combined with in vivo mammalian erythrocyte micronucleus test the animals of the groups treated with 500, 1000 and 2000 mg test material/kg body weight showed no treatment related clinical signs of toxicity or mortality. Blood was sampled 0.5, 1, 2, 4 and 6 h after the second dose of toxicokinetic animals dosed with the vehicle and the highest concentration of the test material. Vehicle dosed animals showed levels below the lower limit of quantification in the plasma. All test material dosed animals showed increased levels of the test material in the plasma, confirming systemic exposure.


Overall, absorption via the oral route is seen in the above-mentioned test.


 


Estimation of dermal absorption:


In two early acute dermal toxicity studies in rats no mortality were observed at the highest doses tested (2000 and 1164 mg/kg). Mild erythema and edema was reported at 2000 mg/kg.


Overall, absorption via the dermal route is anticipated to be low based on the low Log Pow and the low acute toxicity.


 


Estimation of absorption via inhalation:


In an early and limited acute inhalation study no mortality or clinical signs were reported after 1 and 4 h exposure to 524 mg/m3 and 520 mg/m3, respectively.


Overall, absorption via the dermal route is anticipated to be low based on the low Log Pow and the low acute toxicity.


 


Estimation of distribution:


Based on the low log Pow (-1.94), the substance is unlikely to distribute into cells and the intracellular concentrations may not be higher than extracellular concentration.


 


Estimation of accumulation:


In general substances with high log P values have long biological half-lives. Substances with log P values of 3 and less would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may be accumulate if exposures are continuous.


Based on the low log Pow (-1.94), accumulation is unlikely.


 


Estimation of metabolism:


In vitro genotoxicity data do indicate genotoxicity. Positive results were reported in all in vitro genotoxicity tests conducted in the absence and in the presence of metabolic activation; Bacterial reverse gene mutation test, mouse lymphoma test and chromosome aberration test. In principle genotoxicity in vitro is observed without S9 mix at lower concentrations than in the presence of metabolic activation. Nevertheless, no conclusive information on potential in vitro metabolism can be drawn from the in vitro genotoxicity studies.


An in vivo mammalian alkaline comet assay (test method: OECD 489) combined with in vivo mammalian erythrocyte micronucleus test (test method: OECD 474) was performed based on the final decision on the testing proposal (communication number TPE-D-2114546045-54-01/F; Reference: Jacobs, 2022, Combined micronucleus and alkaline comet test). For the comet assay the following tissues were analysed: liver, glandular stomach, and duodenum.


Under the experimental conditions described for the in vivo micronucleus study, the test material is not clastogenic or aneugenic in the bone marrow micronucleus test of male rats up to a dose of 2000 mg/kg bw (the maximum recommended dose in accordance with current regulatory guidelines).


Under the experimental conditions described for the in vivo comet assay, the test material is not genotoxic in the comet assay in liver and glandular stomach cells. The assay was equivocal in duodenum cells as there as a significant dose-response shown however within historical control range of the vehicle control.


No indication of systemic genotoxic activity of the parent compound or a metabolite was reported in the in vivo genotoxicity test. 


 


Estimation of excretion:


Characteristics favourable for urinary excretion are low molecular mass (below 300 g/mol in the rat), good water solubility and ionization of the molecule at the pH of urine.


No assumption on the route of excretion is possible.