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Diss Factsheets
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EC number: 200-002-3 | CAS number: 50-01-1
- 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 88.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The applied total assessment factor is 25.
The relevant dose descriptor, a NOAEC of 88.2 mg/m³ (8h-TWA) was calculated by route-to-route extrapolation from the oral NOAEL of 100 mg/kg bw/day.
Further justification is given in the discussion.
- 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 is 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
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
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- 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 discussion.
- 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 according to TGD 8.
- AF for intraspecies differences:
- 5
- Justification:
- The default factor of 5 for workers 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)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
General considerations
Acute toxicity
For Guanidine hydrochloride an acute toxicity hazard leading to a classification according to CLP (EU-GHS) Regulation (EC) No1272/2008 acute toxicity Category 4 for the oral and inhalation route has been identified. The findings from acute oral toxicity studies suggest that the Guanidine ion exhibits a primary effect on the central nervous / neuromuscular system. However, effects were observed in the range of classification Hazard Category 4, no clear NOAEL could be identified.
No hazard leading to classification was identified for dermal acute toxicity.
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 was 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.
Irritation/ corrosion
Based on the available in vivo data from a skin irritation study Guanidine hydrochloride is classified irritating to the skin (Category 2).
The substance is classified as irritating to the eye by legal binding classification. Respiratory irritation was not reported from an acute toxicity study by inhalation route.
Sensitization:
No skin sensitisation potential of Guanidine hydrochloride has been identified in a skin sensitisation study according to 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 hydrochloride.
Allocated hazard category for qualitative assessment:
The most critical effect of guanidine hydrochloride for the allocation of a hazard category to be used for qualitative assessment is the classification as skin and eye irritating with Hazard statements H315 “Causes skin irritation” and H319 “Causes serious eye irritation” according to CLP (EU-GHS) Regulation (EC) No 1272/2008. Hence the low hazard category has to be assigned according to TGD part E.
Derivation of DNELs:
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 hydrochloride 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 hydrochloride is a solid and particle size distribution value D10 is 48.08 µm and D50 value is 139.26 µm. According to the definition of EN 481 particles of≤100 µm belong to the inhalable 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 hydrochloride. Guanidine hydrochloride 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 hydrochloride has occurred. As a consequence it is likely that the substance will also be absorbed if inhaled. This assumption is supported by data from an acute inhalation toxicity study, were systemic effects and death 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 hydrochloride 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 hydrochloride is considered to be low, due to the water solubility of 2150 g/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
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- 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 discussion.
- 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 is 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)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
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
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- 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 discussion.
- 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 according to TGD 8.
- 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)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
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
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- 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 according to TGD 8.
- 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)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
General considerations
Acute toxicity
For Guanidine hydrochloride an acute toxicity hazard leading to a classification according to CLP (EU-GHS) Regulation (EC) No1272/2008 acute toxicity Category 4 for the oral and inhalation route has been identified. The findings from acute oral toxicity studies suggest that the Guanidine ion exhibits a primary effect on the central nervous / neuromuscular system. However, effects were observed in the range of classification Hazard Category 4, no clear NOAEL could be identified.
No hazard leading to classification was identified for dermal acute toxicity.
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 was 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.
Irritation/ corrosion
Based on the available in vivo data from a skin irritation study Guanidine hydrochloride is classified irritating to the skin (Category 2).
The substance is classified as irritating to the eye by legal binding classification. Respiratory irritation was not reported from an acute toxicity study by inhalation route.
Sensitization:
No skin sensitisation potential of Guanidine hydrochloride has been identified in a skin sensitisation study according to 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 hydrochloride.
Allocated hazard category for qualitative assessment:
The most critical effect of guanidine hydrochloride for the allocation of a hazard category to be used for qualitative assessment is the classification as skin and eye irritating with Hazard statements H315 “Causes skin irritation” and H319 “Causes serious eye irritation” according to CLP (EU-GHS) Regulation (EC) No 1272/2008. Hence the low 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 hydrochloride. Guanidine hydrochloride 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 hydrochloride has occurred. As a consequence it is likely that the substance will also be absorbed if inhaled. This assumption is supported by data from an acute inhalation toxicity study, were systemic effects and death 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 hydrochloride 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 hydrochloride is considered to be low, due to the water solubility of 2150 g/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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