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EC number: 208-060-1 | CAS number: 506-93-4
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 88.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
No dose descriptor for the inhalation route is available;
therefore route to route extrapolation is used to convert the oral NOAEL.
Detailed information is given in the additional information - worker.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default factor for extrapolation sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- It is not necessary to apply an allometric scaling factor because the starting point has been corrected for differences in respiratory volume and this takes account of differences in metabolic rates.
- AF for other interspecies differences:
- 2.5
- Justification:
- Due to the absence of toxicokinetic data an additional factor of 2.5 for other interspecies differences is applied according to TGD 8.
- AF for intraspecies differences:
- 5
- Justification:
- The default factor of 5 for workers will therefore be used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted according to modern regulatory standards and were adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 10.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
- Explanation for the modification of the dose descriptor starting point:
No dose descriptor for the inhalation route is available;
therefore route to route extrapolation is used to convert the oral NOAEL.
Detailed information is given in the additional information - worker.
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No dose descriptor for the dermal route is available;
therefore route to route extrapolation is used to convert the oral NOAEL. Detailed information is given in the additional information - worker.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default factor for extrapolation sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- Due to the absence of toxicokinetic data an additional factor of 2.5 for other interspecies differences is applied.
- AF for intraspecies differences:
- 5
- Justification:
- The default factor of 5 for workers will be used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
General considerations
Short-term data
Data on acute toxicity are available for the oral, inhalation and dermal route. Guanidine nitrate has to be classified for acute oral and inhalation toxicity Hazard Category 4. No classification is required for the dermal route.
Long-term data
Data relevant for long-term toxicity are available from an oral sub-chronic toxicity study and a developmental toxicity study, both in rats.
For Developmental toxicity a NOAEL of 350 mg/kg bw/day was established, no effects on prenatal data, litter data, foetal external, visceral, skeletal and craniofacial parameters were observed up to the highest dose level. Maternal toxicity was observed at 450 and 350 mg/kg bw/day based on mortality (450 mg/kg bw/day) and statistically significantly reduced body weight gain and food consumption. The NOAEL for maternal toxicity is 150 mg/kg bw/day.
A NOAEL of 100 mg/kg bw/day was derived from sub-chronic toxicity study, based on a nephropathy observed at 300 mg/kg bw/day. A (NOEL) could not be established, due to the local irritant effects of Guanidine hydrochloride in the glandular stomach of all dose groups.
Taken together the relevant dose descriptor used as starting point for DNEL derivation is the lowest NOAEL of 100 mg/kg bw/day.
For derivation of DNEL see attached document chapter 13.2 "DNEL derivation for fertility and developmental toxicity".
Irritation/ corrosion
In vivo data from a skin irritation study does not indicate a requirement for classification. However, under stressed conditions like an occlusive dressing, abraded skin or extended exposure for 24 hours skin irritation was observed.
Data from an in-vivo eye irritation study indicate only mild irritating effects but since they are not reversible in one animal, guanidine nitrate has to be classified with H318 “Causes serious eye damage”; Category 1 according to CLP (EU-GHS) Regulation (EC) No 1272/2008. Respiratory irritation was not reported from two acute toxicity studies by inhalation route.
Sensitization:
No skin sensitization potential of Guanidine Nitrate has been assessed in a skin sensitization study using the Buehler method.
Genetic toxicity:
The results from gene mutation assays in bacteria and mammalian cells, as well as chromosome aberration in mammalian cells are consistently negative. Thus, there is no evidence for a genotoxic potential of guanidine nitrate.
Allocated hazard category for qualitative assessment:
The most critical effect of guanidine nitrate for the allocation of a hazard category to be used for qualitative assessment is the classification with H318 “Cause serous eye damage”; Category 1 according to CLP (EU-GHS) Regulation (EC) No 1272/2008. Thus the moderate hazard category has to be assigned according to TGD part E.
DNELlong –term systemic inhalation
Route to route extrapolation oral to inhalation
Starting point: NOAEL (rat) of 100 mg/kg bw/day from sub-chronic toxicity study
For the derivation of a NOAEC for worker the following corrections have to be applied to the oral NOAEL (rat).
The oral NOAEL (rat) is multiplied with 1/0.38 m³/kg bw/8h (default respiratory volume in rat, table R.8.2 of CSR guidance) to give the corresponding rat inhalation 8h-NOAEC (no-observed adverse effect concentration).
To obtain the starting point for workers, a factor of 0.67 is applied to the NOAEC to account for the differences in inhalation rates between animals at rest and humans involved in light activity.
Due to the absence of route specific information a default factor of 2 is included by assuming 50 % for oral absorption (ABS oral-rat) and 100 % absorption after inhalation (ABS inh-human).
For workers the corrected inhalation NOAEC is calculated according to the following equation:
corrected inhalation NOAEC = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/ wRV1
= 100 x 1/0.38 x 50/100 x 6.7/10
The corrected inhalation NOAECworker(8h) is therefore:
= 88.2 mg/m3(8h-TWA)
DNELshort –term systemic inhalation
For guanidine nitrate an acute toxicity hazard leading to a classification according to CLP (EU-GHS) Regulation (EC) No1272/2008 acute toxicity Category 4 for the inhalation route has been identified. However, a reliable dose descriptor for acute systemic effects could not be derived from the available inhalation studies.
High peak exposure cannot be entirely excluded as guanidine nitrate is a solid and the particle size distribution shows that 9.2 % of particles being < 125 µm and thus belong to the respirable fraction.
Considering high peak exposure the DNEL for acute toxicity was set for a reference period of 15 minutes at 3 times the value (default 3) of the long-term DNEL. This approach is appropriate because similar mechanisms of actions are probably involved in the responses to single and repeated exposure (TGD R8).
DNELlong –term systemic dermal
Route to route extrapolation oral to dermal
Starting point: NOAEL (rat) of 100 mg/kg bw/day from sub-chronic toxicity study
No toxicokinetic studies are available for guanidine nitrate. Guanidine nitrate is soluble in water and has a log P value of -1.7, therefore absorption has to be expected. After oral exposure signs of systemic toxicity including death were observed in acute toxicity studies, thus absorption of guanidine nitrate has occurred. As a consequence it is likely the substance will also be absorbed if it is inhaled. This assumption is supported by read-across data from an acute toxicity study by inhalation route, were systemic effects were observed. As data from a dermal acute toxicity study show no systemic effects at the limit dose of 2000 mg/kg bw/d, guanidine nitrate is expected to be not favourable for dermal absorption. The stratum corneum provides its greatest barrier function against hydrophilic compounds. If water solubility is above 10,000 mg/L and the log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for guanidine nitrate is considered to be low, due to the water solubility of 256,000 mg/L and the log P value of -1.7.
Based on these findings and as a worst case assumption the dermal NOAEL is determined to be equal to the oral NOAEL.
Thus no additional assessment factor deemed necessary for oral-to-dermal extrapolation.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.87 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 43.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
No dose descriptor for the inhalation route is available; therefore route to route extrapolation is used to
convert the oral NOAEL. Detailed information is given in the additional information - general population.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default factor for extrapolation sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- It is not necessary to apply an allometric scaling factor because the starting point has been corrected for differences in respiratory volume and this takes account of differences in metabolic rates.
- AF for other interspecies differences:
- 2.5
- Justification:
- Due to the absence of toxicokinetic data an additional factor of 2.5 for other interspecies differences is applied according to TGD 8.
- AF for intraspecies differences:
- 10
- Justification:
- The default factor of 10 for general population will therefore be used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key studies were conducted according to modern regulatory standards and were adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No additional AF was deemed necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No dose descriptor for the dermal route is available;
therefore route to route extrapolation is used to convert the oral NOAEL. Detailed information is given in the additional information - general population.
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default factor for extrapolation sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- Due to the absence of toxicokinetic data an additional factor of 2.5 for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default factor of 10 for general population is used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- The starting point for the DNEL calculation is a NOAEL, therefore the default assessment factor of 1 for a standard procedure is considered appropriate.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default factor for extrapolation sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- Due to the absence of toxicokinetic data an additional factor of 2.5 for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default factor of 10 for general population is used to take account of intraspecies variability.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
General considerations
Short-term data
Data on acute toxicity are available for the oral, inhalation and dermal route. Guanidine nitrate has to be classified for acute oral and inhalation toxicity Hazard Category 4. No classification is required for the dermal route.
Long-term data
Data relevant for long-term toxicity are available from an oral sub-chronic toxicity study and a developmental toxicity study, both in rats.
For Developmental toxicity a NOAEL of 350 mg/kg bw/day was established, no effects on prenatal data, litter data, foetal external, visceral, skeletal and craniofacial parameters were observed up to the highest dose level. Maternal toxicity was observed at 450 and 350 mg/kg bw/day based on mortality (450 mg/kg bw/day) and statistically significantly reduced body weight gain and food consumption. The NOAEL for maternal toxicity is 150 mg/kg bw/day.
A NOAEL of 100 mg/kg bw/day was derived from sub-chronic toxicity study, based on a nephropathy observed at 300 mg/kg bw/day. A (NOEL) could not be established, due to the local irritant effects of Guanidine hydrochloride in the glandular stomach of all dose groups.
Taken together the relevant dose descriptor used as starting point for DNEL derivation is the lowest NOAEL of 100 mg/kg bw/day.
For derivation of DNEL see attached document chapter 13.2 " DNEL derivation for fertility and developmental toxicity".
Irritation/ corrosion
In vivo data from a skin irritation study does not indicate a requirement for classification. However, under stressed conditions like an occlusive dressing, abraded skin or extended exposure for 24 hours skin irritation was observed.
Data from an in-vivo eye irritation study indicate only mild irritating effects but since they are not reversible in one animal, guanidine nitrate has to be classified with H318 “Causes serious eye damage”; Category 1 according to CLP (EU-GHS) Regulation (EC) No 1272/2008. Respiratory irritation was not reported from two acute toxicity studies by inhalation route.
Sensitization:
No skin sensitization potential of Guanidine Nitrate has been assessed in a skin sensitization study using the Buehler method.
Genetic toxicity:
The results from gene mutation assays in bacteria and mammalian cells, as well as chromosome aberration in mammalian cells are consistently negative. Thus, there is no evidence for a genotoxic potential of guanidine nitrate.
Allocated hazard category for qualitative assessment:
The most critical effect of guanidine nitrate for the allocation of a hazard category to be used for qualitative assessment is the classification with H318 “Cause serous eye damage”; Category 1 according to CLP (EU-GHS) Regulation (EC) No 1272/2008. Thus the moderate hazard category has to be assigned according to TGD part E.
DNELlong –term systemic inhalation
Route to route extrapolation oral to inhalation
Starting point: NOAEL (rat) of 100 mg/kg bw/day from sub-chronic toxicity study
For the derivation of a NOAEC for the general population the following corrections have to be applied to the oral NOAEL (rat). Due to the absence of route specific information a default factor of 2 is included by assuming 50 % for oral absorption (ABS oral-rat) and 100 % absorption after inhalation (ABS inh-human).
For general population in case of 24h exposure/d the corrected inhalation NOAEC is calculated according to the following equation:
corrected inhalation NOAEC = oral NOAEL x 1/sRVrat1 x ABSoral-rat/ ABSinh-human
= 100 x 1/1.15 x 50/100
The corrected inhalation NOAECgeneral population(24h) is therefore:
= 43.5 mg/m3
DNELlong –term systemic dermal
Route to route extrapolation oral to dermal
Starting point: NOAEL (rat) of 100 mg/kg bw/day from sub-chronic toxicity study
No toxicokinetic studies are available for guanidine nitrate. Guanidine nitrate is soluble in water and has a log P value of -1.7, therefore absorption has to be expected. After oral exposure signs of systemic toxicity including death were observed in acute toxicity studies, thus absorption of guanidine nitrate has occurred. As a consequence it is likely the substance will also be absorbed if it is inhaled. This assumption is supported by read-across data from an acute toxicity study by inhalation route, were systemic effects were observed. As data from a dermal acute toxicity study show no systemic effects at the limit dose of 2000 mg/kg bw/d, guanidine nitrate is expected to be not favourable for dermal absorption. The stratum corneum provides its greatest barrier function against hydrophilic compounds. If water solubility is above 10,000 mg/L and the log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for guanidine nitrate is considered to be low, due to the water solubility of 256,000 mg/L and the log P value of -1.7.
Based on these findings and as a worst case assumption the dermal NOAEL is determined to be equal to the oral NOAEL.
Thus no additional assessment factor deemed necessary for oral-to-dermal extrapolation.
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