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Guanidinium kation as relevant species for assessment

Dissolution of solid Guanidine carbonate will release Guanidine (CAS 113-00-8) and inorganic carbonate (CAS 3812-32-6). Both substances will then undergo fast speciation. This is discussed in more detail in the section on the dissociation constant.

Carbonate is considered nontoxic and omnipresent in environmental media and biota. Its release caused by the submission item is assumed irrelevant as its quantity seems negligible compared to background concentrations.

Guanidine can exist in the neutral and the protonated form, depending on pH. Fresh surface waters have pH values in the range 4-9, whereas marine environments have a stable pH of about 8. pH normally varies between 5.5 and 7.5 for agricultural soils and sewage treatment plant tanks (ECHA 2008, p. 172). To define the environmentally relevant pH, values from 4-9 in waters seem suitable (OECD TG 111), but the Council Directive 91/414/EEC (of 15 July 1991, consolidated version as of 2011-08-01) extends the range for data requirements to 4-10, probably to cover extreme soils, as this directive relates to Plant Protection Products. Water solute Guanidine is a strong organic base existing primarily as Guanidinium kation at physiological pH (Budaravi 1996), which is 7.3-7.4 (Waugh & Grant 2007). The microspecies distribution calculation of MarvinSketch 5.3.6 (see sections on Partition coefficient and Dissociation constant) suggests the same (100 % Guanidinium kation) for the full range of environmental pH, i.e. 4-10. This is in line with the reported guanidine pKa of ca. 12.5.

Accordingly the subject of the environmental fate discussion is the Guanidine part, present as the Guanidinium kation.

Natural occurrence of Guanidine

Guanidine occurs in plants and was found in seedlings of the common tare (Vicia sativa) the earliest by Schulze (1892). The Merck Index 12th edition (Budaravi 1996, entry 4591, p 778) summarizes evidence for natural occurrence in turnip juice, mushrooms, corn germ, rice hulls, mussels and earthworms. The Kyoto Encyclopedia of Genes and Genomes (KEGG, as of May 2012) lists Guanidine as compound C17349. It is involved in reaction R09785 of the enzyme L-arginine, 2-oxoglutarate:oxygen 5-oxidoreductase (EC The reaction catalyzed is 2-Oxoglutarate + L-Arginine + Oxygen <=> Succinate + CO2 + Guanidine + (S)-1-Pyrroline-5-carboxylate + H2O. Reynolds (1993) summarizes, that Guanidine is found in the urine as a normal product of protein metabolism.

Regarding only the urine of human adults, which contains ca. 0.5 mg Guanidine (Stein & Micklus 1973) in healthy control individuals, and the latest consolidated European population (EU-27) of 497'686'132 (as of 1 January 2008 according to Eurostat) with an adult (15 to 64 years old) proportion of 67.0 % (Eurostat, as of 2010, for comparison 66.7 % in 1990), the release is about 497686132 •0.67 •365 •0.5 mg/year = 60854571790.3 mg/year = 60.85 tonnes/year. Assumed that the remaining population produces the half amount, the figure are 497686132 •0.33 •365 •0.5/2 mg/year = 14986573649.85 mg/year = 14.99 tonnes/year. In sum the human excretion amounts to ca. 76 tonnes per year. The actual biological release estimation should include livestock, pets and wildlife animals as well. Thus it seems justified to estimate the environmental contamination from biota to be surely significantly higher 100 tonnes/year.

It seems unlikely that a naturally occurring substance, suitable as nitrogen source and produced in such amounts would not be intensively used by microorganisms and plants. Nonetheless the preferred nitrogen sources are ammonium/ammonia (CAS 7664-41-7/CAS 14798-03-9) or nitrate (CAS 147-55-8) or the urea (CAS 57-13-6) from which they will rapidly originate and which is in much higher amounts contained in animal excreta or manure materials used as fertilizers in agriculture.

Fate in Soil

If released to soil, guanidine is expected to be mobile based upon an estimated Koc of 20. The pKa of guanidine is 12.5, indicating that this compound will exist almost entirely as a kation in the environment. As a result, guanidine may have greater adsorption and less mobility than its estimated Koc value indicates since kations generally adsorb more strongly to soils containing organic carbon and clay than neutral species. Volatilization from moist soil surfaces is not an important fate process since kations do not volatilize. Guanidine may volatilize from dry soil surfaces based upon its estimated vapour pressure. Guanidine was degraded in soil samples maintained under aerobic conditions at varying rates which were dependent upon the initial guanidine soil concentration (HSDB 2008).

As urea and synthetic mineral fertilizers tend to get leached out contaminating the ground water or get transformed to form nitrous oxide (CAS 10024-97-2) destroying the ozone layer, Guanidines were evaluated in laboratory studies as a less mobile and more stable alternative (Praveen-Kumar & Brumme 1999). In soils, which were pre-treated to have a maximum urea turnover rate after a growth period for the urea transforming microorganism population, a more or less long lag phase was observed for a number of Guanidine salts (Lees H, Quastel 1946). This indicates that the Guanidine transformation competence was (still) present and the soil community was able to switch. This makes sense as nitrogen is often the liming growth factor but generally mobile and only shortly available. Thus rapid environmental biotransformation of Guanidines and their regular use as nitrogen source is considered a common competence of environmental microorganism populations. Altogether fast biodegradation in soils is evidenced by a number of study results and complete biodegradation (ultimate biodegradation) takes place with DT 50 < 16 days (corresponding to a degradation of > 70 % within 28 days). Terrestrial bioaccumulation is not expected.

Aquatic fate

If released into water, guanidine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. However, guanidine has a pKa of 12.5 and will exist almost entirely as a kation under environmental conditions (pH 5-9). As a result, guanidine may have greater adsorption to suspended solids and sediment than its estimated Koc value indicates. Volatilization from water surfaces will not be an important fate process since kations do not volatilize (HSDB 2008).

Mineralisation of guanidine in surface waters is experimentally evidenced (Mitchell 1987 Chemosphere), but with a considered overall DT50 of 33 days somewhat slower than in soils. The author tested the Guanidine transformation rates before and after the release point of a factory with slightly increase degradation in adapted surface freshwater microorganism communities. This suggests that adaptation plays a minor role, which is in line with the assumption the Guanidine use is a standard option in the environment.

In the light of those considerations it is not astonishing that Guanidine compounds fail to show biodegradation in standard test designs (OECD TG 301). This is due to the fact that the test medium contains the more ready usable inorganic nitrogen as ammonium chloride (CAS 12125-02-9) in excess, which makes the Guanidine transformation inefficient and superfluous.

BCF values of <0.1 to 0.1 measured in fish suggest bioconcentration in aquatic organisms is low (HSDB 2008). Hydrolysis or direct photodegradation are irrelevant environmental fate process.

Fate in the Air

If released to air, an estimated vapour pressure of 293 Pa at 25 °C indicates guanidine will exist solely as a vapour in the ambient atmosphere. Vapour-phase guanidine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 9 hours. Guanidine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight (HSDB 2008).

  • Budaravi S, O'Neil MJ, Smith A, Heckelman PE, Kinneary JF eds (1996). The Merck Index. An encyclopedia of Chemicals, Drugs, and Biologicals. 12th Edition, Merck and Co Inc. Whitehouse Station, NJ, USA. ISBN 0911910-12-3. 1741 pages
  • ECHA European Chemicals Agency (2008). Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance. Self-published. 428 p
  • HSDB Hazardous Substances Databank (2008). GUANIDINE, CASRN: 113-00-8, Number: 7603. Last Revision Date: 2008-08 -26, Last Review Date: Reviewed by SRP 5/8/2008, Update History: Complete Update on 2008 -08-26, 38 fields added/edited/deleted, Created 2007-12-13
  • Schulze E (1892). Über das Vorkommen von Guanidin im Pflanzenorganismus. DOI: 10.1002/cber.189202501105 Berichte der deutschen chemischen Gesellschaft 25(1)658–61
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  • Stein IM, Micklus MJ (1973). Concentrations in Serum and Urinary Excretion of Guanidine, 1-Methylguanidine, and 1,1 -Dimethylguanidine in Chronic Renal Failure. PMID: 4705174 Clin Chem 19(6):583-5
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