Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
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: 214-230-6 | CAS number: 1115-70-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Biodegradation in water: screening tests
Administrative data
Link to relevant study record(s)
- Endpoint:
- biodegradation in water: ready biodegradability
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OTS 796.3260 (Ready Biodegradability: Modified Sturm Test)
- Qualifier:
- according to guideline
- Guideline:
- other: FDA TAD 3.11
- GLP compliance:
- yes
- Oxygen conditions:
- aerobic
- Inoculum or test system:
- sewage, domestic, non-adapted
- Details on inoculum:
- The inoculum used in this study consisted of activated sludge and secondary effluent collected from the Columbia Wastewater Treatment Plant on June 23, 1994. These inocula were aerated, blended, settled, and then filtered through glass wool. The filtrate was retained. The inoculum was added to the test solutions at a concentration of 1% blended and filtered activated sludge and 1 % blended and filtered secondary effluent.
- Duration of test (contact time):
- 28 d
- Initial conc.:
- 10 mg/L
- Based on:
- test mat.
- Parameter followed for biodegradation estimation:
- CO2 evolution
- Remarks:
- and other 14C-organic volatiles
- Details on study design:
- Three separate media, designated control, reference, and test were prepared and added to each corresponding reaction vessel. A total of 9 systems (3 replicates x 3 treatments) were prepared. Each of the reaction flasks was connected to a series of traps. The organic 14C-volatiles produced in the test systems were trapped in the ethylene glycol traps. The CO2 produced in the test systems and reference systems was trapped in the 1 N KOH traps. The test chemical medium was prepared by adding 8.55 mL of a 2.00 mg/mL nonradiolabeled metformin HCl solution (equivalent to 4.964 mg C), 0.250 mL of 0.502 mg/mL of 14C-metformin HCl solution (equivalent to 0.036 mg C), 5 mL of activated sludge inoculum, and 5 mL of secondary effluent inoculum into 500 mL of mineral salt solution. The reference chemical medium was prepared by adding 6.125 mL of a 2.00 mg/mL nonradiolabeled dextrose solution (equivalent to 4.899 mg C), 0.080 mL of 14C-glucose (equivalent to 0.100 mg C), 5 mL of activated sludge inoculum, and 5 mL of secondary effluent inoculum into a 500 mL volumetric flask, and bringing the contents to volume with mineral salt solution. The blank control medium was prepared by adding 5 mL of activated sludge inoculum and 5 mL of secondary effluent inoculum into a 500 mL volumetric flask and bringing the contents to volume with mineral salt solution. Three 110 mL volumes of each stock solution prepared as above were added to their corresponding study flasks. Then 10.0-mL aliquots were taken from each study flask for future analyses (pH measurement, LSC, microbial). A portion of the 3 test 10.0-mL aliquots was filtered and analyzed by HPLC. The applied 14C-activity of test and reference chemicals were verified by analyzing triplicate 0.5-mL aliquots of test and reference medium. The pH of all reaction media were measured using pH paper (Baxter S/Pm 0-14.0 pH Indicator strips).
Microbial Evaluation:
Microbial activity was determined by conducting aerobic bacterial count analysis at the study's initiation and termination. Plate count agar (Difco Laboratories, Detroit, MI) was used for the microbial evaluation. A standard microbial plate count was performed on a sample of each of the test solutions (test, reference, and control) as described in the previous section "Initiation". At termination, standard microbial plate count was performed for each of the three test systems. Also, standard microbial plate count was performed for a composite of the reference systems and a composite of the control systems. A dilution scheme that consisted of 10'2, 10', and 10's dilutions of the solutions were used. The plates were prepared and incubated in an environmental chamber at approximately 21 °C.
Sampling Procedure
Samples were taken for 14C-volatile and'4CO2 analysis on days 1, 3, 7, 14, 21, and 28. Both ethylene glycol and KOH trapping vials were sampled and refilled with 20 mL of the appropriate trapping solutions. Triplicate aliquots (0.5-mL for KOH and 1-mL for ethylene glycol) of the trapping solutions were taken for LSC analysis.
Study Termination
On day 28, the pH of test media were measured with an Orion pH meter (Boston, MA). Triplicate 0.5-mL aliquots of the media were taken for LSC analysis. A portion of each test media was filtered and analyzed by HPLC. - Reference substance:
- other: 14C-glucose-UL
- Key result
- Parameter:
- % degradation (CO2 evolution)
- Value:
- 0.6
- Sampling time:
- 28 d
- Details on results:
- After the 28 days of incubation, 80.5% of the applied reference compound (14C-glucose-UL) was mineralized to CO2, verifying that the microbial inoculum was viable and active. For the test chemical 14C-metformin HCl, approximately 0.6% of the applied 14C-activity was mineralized to 14CO2 during the same incubation period.
At the end of study, the degradation of parent test compound was monitored by high-performance liquid chromatography (HPLC). Results showed that the test compound 14C-metformin HCl was not biotransformed (degraded) during the 28-day incubation period.
The overall 14C-mass balance was taken as a summation of the 14C-activity in CO2 produced, 14C-activity in organic volatiles produced, and 14C-activity remaining in the water medium. The 14C-mass balance of 14C-metformin HCl test chemical and 14C-glucose reference chemical averaged 99.8 ± 2.8% and 85.1 ± 8.3%, respectively.
The test results indicated that 14C-metformin was not biodegradable under the test conditions. - Validity criteria fulfilled:
- yes
- Interpretation of results:
- under test conditions no biodegradation observed
- Conclusions:
- The test results indicated that 14C-metformin was not readily biodegradable under the test conditions.
- Executive summary:
Study Design
The test chemical, 14C-metformin HCl, was tested for biodegradability in water at a dosing concentration of 10 mg C/L. Production of 14O2and other 14C-organic volatiles was measured during the 28-day test period. A reference chemical (14C-glucose) at a dosing concentration of 10 mg C/L was tested concurrently to verify the viability of the microbial inoculum.
The study was conducted in the dark at a temperature range of 21 ± 1°C. The percent biodegradability was calculated as a function of the 14CO2 production in the test systems as compared to the amount of applied 14C-activity.
Results
After the 28 days of incubation, 80.5% of the applied reference compound (14C-glucose-UL) was mineralized to 14CO2, verifying that the microbial inoculum was viable and active. For the test chemical 14C-metformin HCl, approximately 0.6% of the applied 14C-activity was mineralized to 14CO2during the same incubation period.
At the end of study, the degradation of parent test compound was monitored by high-performance liquid chromatography (HPLC). Results showed that the test compound 14C-metformin HCl was not biotransformed (degraded) during the 28-day incubation period.
The overall 14C-mass balance was taken as a summation of the 14C-activity in CO2 produced, 14C-activity in organic volatiles produced, and 14C-activity remaining in the water medium. The 14C-mass balance of 14C-metformin HCl test chemical and 14C-glucose reference chemical averaged 99.8 ± 2.8% and 85.1 ± 8.3%, respectively.
Conclusion
The test results indicated that 14C-metformin was not biodegradable under the test conditions.
- Endpoint:
- biodegradation in water: inherent biodegradability
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 302 C (Inherent Biodegradability: Modified MITI Test (II))
- Deviations:
- yes
- Remarks:
- The test was run for 95 days
- GLP compliance:
- yes
- Oxygen conditions:
- aerobic
- Inoculum or test system:
- activated sludge, domestic, non-adapted
- Details on inoculum:
- - Source of inoculum/activated sludge: Werdhölzli WWTP (Zurich, Switzerland)
- Duration of test (contact time):
- 95 d
- Initial conc.:
- 38.5 mg/L
- Based on:
- test mat.
- Parameter followed for biodegradation estimation:
- O2 consumption
- Details on study design:
- Metformin hydrochloride was added at 38.5 mg MET-HCl/L (corresponding to 30 mg MET/L) to OECD 302 C medium containing 100 mg (dry matter) rinsed activated sludge/L.
Note only one activated sludge was used as the inoculum, from Werdhölzli WWTP (Zurich, Switzerland) treating predominantly domestic wastewaters.
Biochemical oxygen demand (BOD) was measured with OxiTop®-C measuring heads (WTW Wissenschaftlich-Technische Werkstätten, Weilheim, Germany).
Ten such vessels with 200 mL working volume (520 mL total volume) were set up: four test vessels (three as required by the guideline plus one as a standby for redundancy/safety reasons); two blank replicates containing inoculum and medium; two procedure control replicates containing inoculum, medium and 100 mg sodium benzoate/L; one abiotic sterile control replicate containing MET, deionized water and 0.2 mM HgCl2 as a sterilizing agent to prevent microbial decomposition; and one toxicity control replicate (which is not normally performed for the OECD 302 C test) containing inoculum, test medium, MET and sodium benzoate as biodegradable reference item.
In addition, four further test vessels with 1800 mL working volume (2000 mL total volume) without BOD measurement were set up with the same sludge, for weekly substance analytics: two replicates containing inoculum, test medium and MET as test systems, plus two replicates containing inoculum and test medium only as blank. All 14 test vessels were stirred using magnet bars and kept in a climate-controlled room at 22±1 °C in the dark for 95 days.
Substance analytics were set up for both MET and GUU, to elucidate the fate of both compounds, following the method recently described by Trautwein et al. [2014]. HPLC analysis of MET and GUU was performed weekly using the same method described further below for the OECD 301F test. The four additional vessels were also used for determination of DOC using a Shimadzu TOC-Analyzer TOC-L CSH (Shimadzu, Reinach, Switzerland), nitrite (photometry according to guidelines of EDI, the Swiss Federal Department of Home Affairs, Berne, Switzerland) and nitrate (Metrohm 930 Compact Ion Chromatography Flex system, Metrohm, Zofingen, Switzerland). - Reference substance:
- benzoic acid, sodium salt
- Key result
- Parameter:
- % degradation (DOC removal)
- Value:
- > 95
- Sampling time:
- 95 d
- Details on results:
- Biodegradation of MET as measured by average blank-corrected BOD/ThOD in the three test vessels proceeded in five phases (see Figure):
First, a lag phase with an insignificant 0e5% BOD/ThOD (NO3) until day 8; second, an initial degradation phase from day 8 to 18, when degradation increased to 25e30%; third, a plateau at that level without further significant oxygen uptake from day 18 to 42; fourth, a second degradation phase from day 42 to 64, when 70% BOD/ThOD (NO3) was reached; and last, a second plateau phase from day 64 to 95, with BOD/ThOD (NO3) undulating between 62 and 71%.
The toxicity control showed the same pattern as the averaged three test vessels, with 45% combined degradation reached during day 4 and 65% on day 14; from day 49 to 95, the total degradation showed a plateau around 85-93% (not shown).
In the parallel set of test vessels without BOD measuring units (see Figure), the blank-corrected DOC was stable for the first seven days, then showed a decrease to approximately 60% of the starting level in parallel with the initial BOD degradation phase, followed by a plateau from day 14 to 35 with slightly increasing DOC levels, then a second decrease from day 35 to 42 (one week earlier than the second degradation phase in the BOD vessels) to <10% of initial
DOC, finally a slower decrease from day 42 to 56 to DOC values < LOQ, corresponding to >95% removal by DOC loss. Blankcorrected metformin concentrations showed an initial decline by nearly 10% of initial from day 0 to 7, then a strong decrease to < LOQ from day 7 to 14, with a minor peak of <5% of initial from days 35 to 56, then consistently < LOQ until day 95. Blank-corrected GUU concentrations started with 0 (Nitrite remained below LOQ on most sampling days (except day 14, not shown). Nitrate formation showed an opposite pattern to MET and GUU degradation; from day 7 onwards, nitrate increased to reach a plateau around day 21, this was followed by a second increase from day 35 to reach a second plateau approximately on day 56 (Fig. 2b)
Based on the measurements, full nitrification proceeded slower than the degradation of either MET or GUU. - Results with reference substance:
- The positive control, sodium benzoate, reached 71% degradation by BOD/ThOD in 7 days, evidencing awell degrading AS, and reached a plateau between 85 and 90% on day 20.
- Validity criteria fulfilled:
- yes
- Interpretation of results:
- inherently biodegradable
- Conclusions:
- This prolonged inherent biodegradation test strongly suggests not only primary transformation of metformin to guanyl urea, but also subsequent full mineralization of GUU, with both degradation phases starting after a clear lag phase.
- Executive summary:
This prolonged inherent biodegradation test strongly suggests not only primary transformation of metformin to guanyl urea, but also subsequent full mineralization of guanyl urea, with both degradation phases starting after a clear lag phase.
Referenceopen allclose all
Description of key information
Based on a GLP-conform ready biodegradability test, metformin HCL is considered to be not readily biodegradable under the test conditions. In a prolonged inherent biodegradation test according to OECD 302C, complete mineralization of metformin HCL and its primary degradation product guanyl urea was observed with both degradation phases starting after a clear lag phase.
Key value for chemical safety assessment
- Biodegradation in water:
- inherently biodegradable
- Type of water:
- freshwater
Additional information
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.