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EC number: 244-599-9 | CAS number: 21829-50-5
- 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:
- 90.3 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 6
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 25.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 24
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Additional information - workers
According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. In the present case, DNELs have been derived according to the ECETOC guidance (ECETOC, Technical Report No. 110, 2010).
No information on absoprtion of tris[(2 -hydroxymethyl)ammonium] citrate is available. In accordance with Chapter R.8 of REACH Guidance on information requirements and chemical safety assesment, a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) is proposed to be used in the case of oral-to-inhalation extrapolation. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.
The substance does not have to be classified for acute toxicity and therefore derivation of a DNELacute is not necessary. The substance is not irritating to skin and eyes and not sensitizing, therefore no DNELs for these endpoints needs to be derived.
Tris[(2 -hydroxyethyl)ammonium] citrate is assessed as being non-mutagenic, non-carcinogenic and non-toxic to reproduction and development; therefore no DNELs have been derived for these endpoints.
For repeated dose toxicity, a NOAEL of 614.6 mg/kg bw/day, based on the read-across with monoethanolamine, will be taken forward to DNEL derivation. This value is based on the results of the oral 2 -generation reproductive toxicity study with monoethanolamine, in which signs of systemic toxicity were observed in parental females at the highest dose level of 1000 mg/kg bw/day, manifested as reduced food consumption and/or body weight gain during gestation and lactation. In F1 animals, at 300 mg/kg bw/day and 1000 mg/kg bw/day statistically significant increases of absolute and relative kidney weights were observed; however, these increases were not accompanied by histopathological changes. In F0 and F1 males at 1000 mg/kg bw/day absolute and relative organ weights of cauda epididymidis and epididymides were statistically significantly decreased. Prostate weight and the number of homogenization resistant caudal epididymal sperm were statistically significantly decreased in the F0 males. These findings were not accompanied by histopathological changes. Based on this, a NOAEL of 300 mg/kg bw/day was established for general toxicity of monoethanolamine in the study. Applying a correction for molecular weight and taking into account that 3 moles of monoethanolamine are produced from 1 mole of tris[(2 -hydroxyethyl)ammonium] citrate, a NOAEL of 300× (343.31/3)/61.08 = 614.6 mg/kg bw/day can be calculated for tris[(2 -hydroxyethyl)ammonium] citrate.
Long-term – inhalation, systemic effects (based on 2 -generation reproductive toxicity study in rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 614.6 mg/kg bw/day |
Based on read-across from monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males. |
Step 2) Modification of starting point |
2
0.38 m3/kg bw
6.7 m3/10 m3 |
The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation.
Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2).
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest. |
Modified dose-descriptor |
614.6 / 2 / 0.38 x (6.7/10) = 541.8 mg/m3 |
|
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No assessment factor for allometric scaling needs to be applied in case of oral to inhalation route-to-route extrapolation |
Intraspecies |
3 |
Default assessment factor for workers |
Exposure duration |
1 |
As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required. |
Dose response |
1 |
A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL |
Quality of database |
2 |
Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed. |
DNEL |
Value |
|
|
541.8 / (1 x 3 x 1 x 1 x 2) = 90.3 mg/m3 |
Long-term – dermal, systemic effects (based on 2-generation reproductive toxicity study in rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 614.6 mg/kg bw/day |
Based on read-across from monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males. |
Step 2) Modification of starting point |
1
|
According to Chapter R.8 of the REACH Guidance on information requirements and chemical safety assessment, a default factor of 1 is proposed for the extrapolation from oral to dermal route of absorption |
Modified dose-descriptor |
614.6 x 1 = 614.6 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 |
Assessment factor for allometric scaling in case of a study with rats |
Intraspecies |
3 |
Default assessment factor for workers |
Exposure duration |
1 |
As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required |
Dose response |
1 |
A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL |
Quality of database |
2 |
Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed. |
DNEL |
Value |
|
|
614.6 / (4 x 3 x 1 x 1 x 2) = 25.6 mg/kg bw/day |
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 26.7 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 10
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 15.4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 40
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 15.4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 40
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
Additional information - General Population
According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. In the present case, DNELs have been derived according to the ECETOC guidance (ECETOC, Technical Report No. 110, 2010).
No information on absoprtion of tris[(2 -hydroxyethyl)ammonium] citrate is available. In accordance with Chapter R.8 of REACH Guidance on information requirements and chemical safety assesment,a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) is proposed to be used in the case of oral-to-inhalation extrapolation. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation. These default factors will be taken forward to DNEL derivation.
The substance does not have to be classified for acute toxicity and therefore derivation of a DNELacuteis not necessary. The substance is not irritating to skin and eyes and not sensitizing, therefore no DNELs for these endpoints need to be derived.
Tris[(2 -hydroxyethyl)ammonium] citrate is assessed as being non-mutagenic, non-carcinogenic and non-toxic to reproduction and development; therefore no DNELs have been derived for these endpoints.
For repeated dose toxicity, a NOAEL of 1000 mg/kg bw/day, based on the read-across with monoethanolamine, will be taken forward to DNEL derivation. This value is based on the results of the oral 2 -generation reproductive toxicity study with monoethanolamine, in whichsigns of systemic toxicity were observed in parental females at the highest dose level of 1000 mg/kg bw/day, manifested as reduced food consumption and/or body weight gain during gestation and lactation. In F1 animals, at 300 mg/kg bw/day and 1000 mg/kg bw/day statistically significant increases of absolute and relative kidney weights were observed; however, these increases were not accompanied by histopathological changes.In F0 and F1 males at 1000 mg/kg bw/day absolute and relative organ weights of cauda epididymidis and epididymides were statistically significantly decreased. Prostate weight and the number of homogenization resistant caudal epididymal sperm were statistically significantly decreased in the F0 males. These findings were not accompanied by histopathological changes. Based on this, a NOAEL of 300 mg/kg bw/day was established for general toxicity of monoethanolamine in the study. Applying a correction for molecular weight and taking into account that 3 moles of monoethanolamine are produced from 1 mole of tris[(2 -hydroxyethyl)ammonium] citrate, a NOAEL of 300× (343.31/3)/61.08 = 614.6 mg/kg bw/day can be calculated for tris[(2 -hydroxyethyl)ammonium] citrate.
Long-term – inhalation, systemic effects (based on 2 -generation reproductive toxicity study in rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 614.6 mg/kg bw/day |
Based on read-across from monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males. |
Step 2) Modification of starting point |
2
1.15 m3/kg bw
|
The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation.
Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2). |
Modified dose-descriptor |
614.6/ (2 x 1.15) = 267.2 mg/m3 |
|
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No assessment factor for allometric scaling needs to be applied in case of oral to inhalation route-to-route extrapolation |
Intraspecies |
5 |
Default assessment factor for general population |
Exposure duration |
1 |
As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required. |
Dose response |
1 |
A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL |
Quality of database |
2 |
Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed. |
DNEL |
Value |
|
|
267.2 / (1 x 5 x 1 x 1 x 2) = 26.7 mg/m3 |
Long-term – dermal, systemic effects (based on 2-generation reproductive toxicity study in rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 614.6 mg/kg bw/day |
Based on read-across with monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males. |
Step 2) Modification of starting point |
1
|
According to Chapter R.8 of the REACH Guidance on information requirements and chemical safety assessment, a default factor of 1 is proposed for the extrapolation from oral to dermal route of absorption |
Modified dose-descriptor |
614.6 x 1 = 614.6 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 |
Assessment factor for allometric scaling in case of a study with rats |
Intraspecies |
5 |
Default assessment factor for general population |
Exposure duration |
1 |
As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required |
Dose response |
1 |
A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL |
Quality of database |
2 |
Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed. |
DNEL |
Value |
|
|
614.6 / (4 x 5 x 1 x 1 x 2) = 15.4 mg/kg bw/day |
Long-term – inhalation, systemic effects (based on 2 -generation reproductive toxicity study in rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 614.6 mg/kg bw/day |
Based on read-across with monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreasedabsolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males. |
Step 2) Modification of starting point |
not applicable |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 |
Assessment factor for allometric scaling in case of a study with rats |
Intraspecies |
5 |
Default assessment factor for general population |
Exposure duration |
1 |
As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required |
Dose response |
1 |
A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL |
Quality of database |
2 |
Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed. |
DNEL |
Value |
614.6 / (4 x 5 x 1 x 1 x 2) = 15.4 mg/kg bw/day |
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