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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 241-659-6 | CAS number: 17675-60-4
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- Waiver
- Type of information:
- other: Waiver, based on expert evaluation of the datasets for physical chemistry amd toxicology
- Adequacy of study:
- other information
- Study period:
- 2018
- Reliability:
- other: Expert judgement and interpretation based on detailed examination of the current database for guanylurea phosphate.
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- Waiver based on the expert judgement and interpretation of a detailed examination of the current database for guanylurea phosphate.
- GLP compliance:
- no
- Specific details on test material used for the study:
- Not applicable
- Type:
- absorption
- Results:
- predicted: 80%
- Type:
- excretion
- Results:
- predicted: primarily via the urine and faeces
- Type:
- distribution
- Results:
- predicted: widley distributed
- Type:
- metabolism
- Results:
- predicted: mostly in the liver and kidneys
- Type:
- other: dermal absorption
- Results:
- predicted: low due to the physical chemical characteristics of GUP
- Conclusions:
- The physical chemical characteristics of GUP and the data from the repeat dose toxicity study clearly suggest and demonstrate that GUP is likely to be adequately absorbed, distributed and excreted with limited or no bioaccumulation. The data suggest that the liver and kidneys are likely target organs and that enhanced metabolism is predicted to occur, although the toxicity of metabolites is predicted to be limited, as in the genotoxicity studies metabolic activation was without demonstrable effect. Considering these attributes, the most likely route of excretion would be primarily via the urine and secondarily the faeces. GUP was not acutely toxic via the oral or dermal routes, was not a skin or eye irritant or a skin sensitizer. The data from the repeat dose study demonstrated systemic exposure and that GUP was of very low toxicity and was unlikely to be toxic to reproduction, in utero development of the foetus or post-natal survival and development of neonatal rats.
- Executive summary:
Opinion on TK/ADME (absorption, distribution, metabolism and excretion).
No compound specific toxicokinetic or ADME investigations, or studies on potential metabolites, were available at the time of this review. However, physical chemical data on the test substance and mammalian toxicity data were available for evaluation from which a reasoned scientific opinion on the ADME parameters of Guanylurea phosphate (GUP) can be predicted.
The physical chemical data were generated specifically on the test substance and were generally GLP and regulatory compliant studies.
An on-line literature search (including: PubChem, TOXNET, ChemIDplus, NITE, NICNAS, eChemPortal, NIOSH) did not reveal any further data that might aid in this prediction.
Key physical chemical data on GUP
The data demonstrated that GUP was reasonably soluble in water (91.6 g/L at 20 °C) and had a partition coefficient (Log Kow) of greater than 0 (values were below the limit of the method); the evidence pointing to a relatively lipophobic substance. The vapour pressure was 1.7 x 10-4 Pa at 20 °C, the melting point was approximately 170 °C, flammability was greater than 400 °C, GUP was not surface active, and the particle size was greater than 470 µm (L50 D). These findings do not suggest that this substance would present a risk of inhalation exposure under ambient environmental conditions.
A tabular data summary is given in Table 1.
Mammalian toxicity data on GUP
The mammalian toxicity data evaluated were:
• acute oral and dermal toxicity,
• in vitro skin corrosion/irritation,
• in vitro eye corrosion/irritation,
• in vitro skin sensitization,
• Ames test, in vitro chromosome aberration test and in vitro gene mutation test,
• OECD 422 Combined Repeated Dose Toxicity Study with the Reproduction and Developmental Toxicity Screening Test (oral gavage study).
These studies were GLP and regulatory compliant.
A tabular data summary is given in Table 1.
The acute oral and dermal LD50 were greater than 2000 mg/kg bw it may be reasonably concluded that GUP is not acutely toxic. Furthermore, GUP was neither a skin or eye irritant nor a skin sensitizer. The in vitro genotoxicity studies (with and without S9 metabolic activation) demonstrated that there was no evidence for genotoxic potential.
In an OECD 422 study, combined repeat dose toxicity and reproductive/developmental screening study (oral gavage dosed), where the dosages tested were 0, 100, 300 and 1000 mg/kg bw/day (there was also a 14-day dose ranging study at these dosages) the systemic NOAEL was 1000 mg/kg bw/day. There were no demonstrable adverse effects on systemic toxicity markers. Furthermore, there was no evidence for any effects on mating performance, fertility, gestation, parturition or on neonatal survival and development. There was evidence of systemic exposure, this was demonstrated in the kidneys of male rats at 1000 mg/kg bw/day, where hyaline droplets were observed, these represented an accumulation of secondary lysosomes within the cytoplasm and contained alpha-2u-globulin that has been shown to reversibly bind to the inducing xenobiotics and/or their metabolites. Hyaline droplet deposition is known to be a male rat specific event, and it is of no toxicological relevance in humans.
The data from the acute toxicity studies and sensitization and genotoxicity studies clearly indicate a substance with no overt acute systemic or topical toxicity, skin or eye irritation, skin sensitization potential or genotoxicity. However, systemic toxicity was evident in the repeat dose toxicity study in rats.
Opinion on TK/ADME of GUP
Absorption and distribution
The relative lipophobicity, and water solubility, indicates that the substance may not be rapidly absorbed across lipid bilayer cell membranes (limiting systemic availability), when compared to more lipophilic substances, after either oral or dermal exposure. Although absorption via aqueous channels and passive diffusion, and the fact that GUP has a molecular weight of 200 g/mol, suggest that some absorption would be expected.
With water solubility around 92 g/L and a Log Pow of <0, the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum and as such dermal uptake for this substance might be expected to be low. The data from the acute toxicity studies do not confirm nor refute evidence of acute absorption via the GI tract or skin.
The OECD 422 study demonstrated local toxicity seen as irritation in the stomach, but apparently little, if any, systemic toxicity. However, the finding of hyaline droplets in the kidney of the male rats at 1000 mg/kg bw/day clearly indicates that some systemic exposure was evident.
The data suggest some systemic exposure and indicate that distribution, bioavailability and bioaccumulation might be limited. The physical chemistry data suggest that it is unlikely that acute inhalation exposure (i.e. would not present an exposure risk as significant exposure would not be expected) would result in toxicity considering the very low toxicity evident in the studies presented.
Metabolism
It is predicted, from the both the physical chemistry and toxicity data, that metabolism would be primarily via the liver and secondarily the kidneys. In the OECD 422 study the highest dosage tested showed an increase in hyaline droplets in the kidney of the male rats which suggests an increase in metabolic activity in relation to systemic exposure of GUP. The substance is likely to be extensively metabolised in the liver. Regarding potential metabolites, as no genotoxicity was seen either with or without the addition of metabolic activation (+/- liver S9-mix), that data support the view that potential metabolites of GUP may be of limited mammalian toxicity.
Excretion
Given the physical chemical properties of the substance, the nature of the effects seen in the repeat dose toxicity study and probable limited bioaccumulation, it is predicted that excretion would be primarily via the urine and faeces. It is likely that urinary excretion would be the primary route.
Conclusions
The physical chemical characteristics of GUP and the data from the repeat dose toxicity study clearly suggest and demonstrate that GUP is likely to be adequately absorbed, distributed and excreted with limited or no bioaccumulation. The data suggest that the liver and kidneys are likely target organs and that enhanced metabolism is predicted to occur, although the toxicity of metabolites is predicted to be limited, as in the genotoxicity studies metabolic activation was without demonstrable effect. Considering these attributes, the most likely route of excretion would be primarily via the urine and secondarily the faeces. GUP was not acutely toxic via the oral or dermal routes, was not a skin or eye irritant or a skin sensitizer. The data from the repeat dose study demonstrated systemic exposure and that GUP was of very low toxicity and was unlikely to be toxic to reproduction, in utero development of the foetus or post-natal survival and development of neonatal rats.
Table 1. Data summary for Guanylurea phosphate (GUP)
Physical chemical data
State of the substance at 20° C and 101,3 kPa
White solid with no reported odour.
Melting/freezing point
The test item started to foam at 169 °C (442K) and completely vanished at 175°C (448K). No melting was observed.
Boiling point
Substance is a solid.
Relative density
1.6120 relating to the nominal density of water at 4°C (0.999972 g/cm3)
Vapour pressure
1.7E-04 Pa (20°C), 2.6E-04 Pa (25°C) and 1.8E-03 Pa (50°C).
Surface tension
71.7 mN/m at 19.8°C.
Since the test item showed a surface tension higher than 6 mN/m under the conditions of the method, GUP is not surface active according to Regulation (EC) No. 440/2008Water solubility
91.6 g/L (pH 3.04) at 20°C.
Partition coefficient n-octanol/water
The log Pow values were below the limit of the method (log Pow < 0)
US EPA: logP = -1.29
Flammability
The test item did not exhibit any indication of self-ignition up to and including the maximum temperature of the test method, 400°C. The substance does not have a self-ignition temperature.
Granulometry (particle size distribution)
Volume-based particle size:
L10 D was determined to be 95.31µm
L50 D was determined to be 471.04µm
L90 D was determined to be 1110.54µm.Mammalian toxicity data
Acute toxicity, oral route
LD50cut-off (rat): 2000 mg/ kg bw
Acute toxicity, dermal route
LD50> 2000 mg
Skin irritation (in vitro) EpiDerm
Non-irritant
Eye irritation (in vitro) BCOP
Slight irritation - not classified
Skin sensitisation (in vitro) KeratinoSens
Non-sensitiser.
In vitrogene mutation study in bacteria
Non-mutagenic
In vitrocytogenicity study in mammalian cells
Non-clastogenic
In vitrogene mutation study in mammalian cells
Non-mutagenic
OECD 422 study: Combined Repeated Dose Toxicity Study with the Reproduction and Developmental Toxicity Screening Test
No changes in most of the measured toxicity parameters.
Local irritancy in stomach of rats (M/F), no effects on food consumption. Histopathological evidence corroborated this. Effects not considered as systemic toxicity.
In the stomach, at 1000 mg/kg bw/day, there was minimal to moderate multifocal mixed inflammatory cell infiltrates in the submucosa of the glandular stomach and the limiting ridge; in controls only, slight mixed inflammatory cell infiltrates were observed in the limiting ridge of one rat. This change, at 1000 mg/kg bw/day, was most likely to have been induced by the local irritating effect of the test item and gavage dosing. Additionally, gastric haemorrhage observed in the stomach of one rat at 1000 mg/kg bw/day was considered a local irritating effect of the test item.
In kidneys from male rats at 1000 mg/kg bw/day, hyaline droplets represent an accumulation of secondary lysosomes within the cytoplasm and contain alpha-2u-globulin that reversibly binds to the inducing xenobiotics and/or metabolites. Hyaline droplet deposition is a male rat specific event, and it is of no toxicological relevance in humans.
The Systemic NOAEL of Guanylurea phosphate (GUP) in this study for general toxicity and reproductive toxicity screening is 1000 mg/kg bw/day.
Reference
Description of key information
Key physical chemical data on GUP
The data demonstrated that GUP was reasonably soluble in water (91.6 g/L at 20 °C) and had a partition coefficient (Log Kow) of greater than 0 (values were below the limit of the method); the evidence pointing to a relatively lipophobic substance. The vapour pressure was 1.7 x 10-4 Pa at 20 °C, the melting point was approximately 170 °C, flammability was greater than 400 °C, GUP was not surface active, and the particle size was greater than 470 µm (L50 D). These findings do not suggest that this substance would present a risk of inhalation exposure under ambient environmental conditions.
Mammalian toxicity data on GUP
The mammalian toxicity data evaluated were:
• acute oral and dermal toxicity,
• in vitro skin corrosion/irritation,
• in vitro eye corrosion/irritation,
• in vitro skin sensitization,
• Ames test, in vitro chromosome aberration test and in vitro gene mutation test,
• OECD 422 Combined Repeated Dose Toxicity Study with the Reproduction and Developmental Toxicity Screening Test (oral gavage study).
These studies were GLP and regulatory compliant.
The acute oral and dermal LD50 were greater than 2000 mg/kg bw it may be reasonably concluded that GUP is not acutely toxic. Furthermore, GUP was neither a skin or eye irritant nor a skin sensitizer. The in vitro genotoxicity studies (with and without S9 metabolic activation) demonstrated that there was no evidence for genotoxic potential.
In an OECD 422 study, combined repeat dose toxicity and reproductive/developmental screening study (oral gavage dosed), where the dosages tested were 0, 100, 300 and 1000 mg/kg bw/day (there was also a 14-day dose ranging study at these dosages) the systemic NOAEL was 1000 mg/kg bw/day. There were no demonstrable adverse effects on systemic toxicity markers. Furthermore, there was no evidence for any effects on mating performance, fertility, gestation, parturition or on neonatal survival and development. There was evidence of systemic exposure, this was demonstrated in the kidneys of male rats at 1000 mg/kg bw/day, where hyaline droplets were observed, these represented an accumulation of secondary lysosomes within the cytoplasm and contained alpha-2u-globulin that has been shown to reversibly bind to the inducing xenobiotics and/or their metabolites. Hyaline droplet deposition is known to be a male rat specific event, and it is of no toxicological relevance in humans.
The data from the acute toxicity studies and sensitization and genotoxicity studies clearly indicate a substance with no overt acute systemic or topical toxicity, skin or eye irritation, skin sensitization potential or genotoxicity. However, systemic toxicity was evident in the repeat dose toxicity study in rats.
Opinion on TK/ADME of GUP
Absorption and distribution
The relative lipophobicity, and water solubility, indicates that the substance may not be rapidly absorbed across lipid bilayer cell membranes (limiting systemic availability), when compared to more lipophilic substances, after either oral or dermal exposure. Although absorption via aqueous channels and passive diffusion, and the fact that GUP has a molecular weight of 200 g/mol, suggest that some absorption would be expected.
With water solubility around 92 g/L and a Log Pow of <0, the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum and as such dermal uptake for this substance might be expected to be low. The data from the acute toxicity studies do not confirm nor refute evidence of acute absorption via the GI tract or skin.
The OECD 422 study demonstrated local toxicity seen as irritation in the stomach, but apparently little, if any, systemic toxicity. However, the finding of hyaline droplets in the kidney of the male rats at 1000 mg/kg bw/day clearly indicates that some systemic exposure was evident.
The data suggest some systemic exposure and indicate that distribution, bioavailability and bioaccumulation might be limited. The physical chemistry data suggest that it is unlikely that acute inhalation exposure (i.e. would not present an exposure risk as significant exposure would not be expected) would result in toxicity considering the very low toxicity evident in the studies presented.
Metabolism
It is predicted, from the both the physical chemistry and toxicity data, that metabolism would be primarily via the liver and secondarily the kidneys. In the OECD 422 study the highest dosage tested showed an increase in hyaline droplets in the kidney of the male rats which suggests an increase in metabolic activity in relation to systemic exposure of GUP. The substance is likely to be extensively metabolised in the liver. Regarding potential metabolites, as no genotoxicity was seen either with or without the addition of metabolic activation (+/- liver S9-mix), that data support the view that potential metabolites of GUP may be of limited mammalian toxicity.
Excretion
Given the physical chemical properties of the substance, the nature of the effects seen in the repeat dose toxicity study and probable limited bioaccumulation, it is predicted that excretion would be primarily via the urine and faeces. It is likely that urinary excretion would be the primary route.
Conclusions
The physical chemical characteristics of GUP and the data from the repeat dose toxicity study clearly suggest and demonstrate that GUP is likely to be adequately absorbed, distributed and excreted with limited or no bioaccumulation. The data suggest that the liver and kidneys are likely target organs and that enhanced metabolism is predicted to occur, although the toxicity of metabolites is predicted to be limited, as in the genotoxicity studies metabolic activation was without demonstrable effect. Considering these attributes, the most likely route of excretion would be primarily via the urine and secondarily the faeces.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 80
- Absorption rate - dermal (%):
- 50
Additional information
Oral absorption
The physical chemistry and mammalian toxicity data suggest that oral absorption occurs but that it may be limited. Applying expert judgement to the evaluation of these data a conservative estimate of 80% for oral absorption is suggested.
Dermal absorption
Dermal absorption is likely to be very low but in the absence of experimental data a default value of 50% is suggested based on EFSA guidance - EFSA Journal 2017;15(6):4873).
Inhalation
The physical chemistry data clearly suggest that guanylurea phosphate is unlikely to present an inhalation hazard and therefore absorption via this route may be considered negligible.
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.