Registration Dossier
Registration Dossier
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EC number: 701-402-5 | CAS number: -
- 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:
- 11.67 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):
- 75
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 875 mg/m³
- Explanation for the modification of the dose descriptor starting point:
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) is considered to be 0.4 m³/kg bw. Correction for activity driven differences of respiratory volumes in workers compared to workers in rest was considered to be 6.7 m³/10 m³. Therefore, the modified dose descriptor starting point is 875 mg/m³ (= 1000 / 2 / 0.4 x (7/10)).
- AF for differences in duration of exposure:
- 6
- Justification:
- Difference in duration from subacute to chronic exposure
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- Worker population
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 20 mg/m³
- Most sensitive endpoint:
- carcinogenicity
DNEL related information
- DNEL derivation method:
- other: Based on the DNEL long-term - local effects Inhalation route of 0.5 mg/m³ (= 0.4 ppm).
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 40 mg/m³
- Most sensitive endpoint:
- carcinogenicity
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 33.3 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):
- 300
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on the low Log Kow and the very high water solubility, dermal absorption is expected to be low. A ration of 0.1 for oral to dermal absorption is therefore provisionally suggested for DNEL derivation.
- AF for differences in duration of exposure:
- 6
- Justification:
- Difference in duration from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Rats to humans
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- Worker population
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
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.
Short-term toxicity
According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure. The substance is also not classified as irritating or sensitizing to the skin and therefore no derivation of the DNEL for local dermal effects needs to be derived. No data is available whether the test substance could cause irritation to the respiratory tract and therefore no DNEL could be derived.
Long-term toxicity
A subacute (28-days) oral toxicity study is available in rats. In none of the dose groups treatment related effects were observed on mortality, clinical signs, body weight, food consumption, ophthalmic examinations, clinical pathology investigations, organ weight, macroscopic and microscopic findings. Therefore, a NOAEL of 1000 mg/kg bw was determined. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. The low log Pow value and the high water solubility (>10000 mg/L) suggest that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for these substances will be low. In the absence of route-specific information a ratio of 0.1 for oral to dermal absorption is provisionally suggested for the risk assessment of the substance, based on its physical-chemical properties.
Additionally, for the inhalation route of exposure, acute and long-term, local effects, the DNEL values from formaldehyde were taken into consideration. As worst-case scenario the registered substance contains a maximum of 2.5 % of formaldehyde, therefore, the corresponding DNEL value was modified by a factor 40.
DNEL acute local - inhalation
As regards the DNEL short-term inhalation for workers according to the Guidance on information requirements and chemical safety assessment, Chapter R.8; APPENDIX R. 8-13 (Deriving DNELs, when a community/national occupational exposure limit (OEL) is available) the registrant is allowed to use a national occupational exposure limit in place of developing a DNEL.
A national occupational exposure limit (MAK value) has been adopted. Toxicological information and evaluations of health effects used for setting the national OEL are documented and available (German MAK commission; Greim 2000). The study of Lang et al., 2008 reconfirms the MAK value of 0.3 ppm with a short-term excursion factor of 2 (STEL 0.6 ppm) as no objective signs for sensory irritation were found in volunteers exposed to 0.3 ppm with peaks of 0.6 ppm or at 0.5 ppm over 4 h. Recently Müller et al. (2010) defined the NOAEC in more detail. They did not observe objective or subjective signs of irritation at peak exposure concentrations of 0.8 ppm over 15 min and at 0.7 ppm over 4h. These NOAECs pertained likewise to persons with high and low sensitivity for sensory irritation as determined by CO2threshold. In comparison to the findings of Lang et al. (2007) that peak exposures of 1 ppm lead to sensory irritation, this indicates that any irritation occurring in the range between 0.7 and 1 ppm will rapidly subside and that no irritation will occur at 15 min peaks of 0.8 ppm. Therefore, 0.8 ppm is taken as acute DNEL (15 min).
Formaldehyde DNEL short term inhalation worker exposure = STEL (15 minutes) of 0.8 ppm.
Worker-DNEL long-term for inhalation route-local
Derivation of the worker-DNEL long-term for inhalation route-local is driven by effects on the upper respiratory tract especially taking into consideration the development of nasal tumors in rats. According to the Guidance on information requirements and chemical safety assessment, Chapter R.8; APPENDIX R. 8-13 (Deriving DNELs, when a community/national occupational exposure limit (OEL) is available) the registrant is allowed to use a national occupational exposure limit in place of developing a DNEL.
A national occupational exposure limit (MAK value) has been adopted. Toxicological information and evaluations of health effects used for setting the national OEL are documented and available (German MAK commission; Greim 2000).
The German MAK commission (2000) developed a detailed mode of action for the induction of nasal tumors in rats after inhalation exposure. For cytotoxicity, cell proliferation and nasal tumor development the NOAECs are in the range between 2 and 6 ppm, while for DNA protein cross link formation (DPX) a clear NOEL could not be established. Most importantly, the proliferation rate of the respiratory epithelium is very low and is not increased up to concentrations of 2 ppm. Therefore, the probability of fixation of DPX into permanent mutations is low taking into account the rapid repair of DPX. The commission concluded that the occurrence of tumors is the result of chronic proliferative processes and that the genotoxicity of formaldehyde plays no or at most a minor part in its carcinogenic potential. Under these considerations the MAK value for the workplace was set at 0.3 ppm with a factor of 2 for peak exposures of 15 min and a ceiling of 1 ppm. The avoidance of cell proliferation in the respiratory tract was decisive for defining the MAK value. Cell proliferation is caused by
cytotoxic irritation of formaldehyde, but data on cytotoxic irritation of the respiratory tract are not available for humans. However, the database for sensory irritation to the eye, a more sensitive parameter, was considered sufficient for setting the MAK value at 0.3 ppm. The review of Paustenbach et al. (1997) was an important consideration of the German MAK commission for defining their MAK value of 0.3 ppm. But according to this review and the review of Arts et al., 2007 appreciable subjective symptoms will only be noted at or above 1 ppm.
As all these studies reviewed only relied on subjective symptoms, much more weight has to be given to the more recent investigations of Lang et al. (2007) and Mueller et al. (2010) because the following important aspects were taken into consideration:
- objective signs of irritation, like eye blinking rate or conjunctival redness
- influence of personality factors
- confounding by odor (Lang-study)
- evaluation of subgroups with high and low sensitivity for nasal irritation (Mueller-study).
The NOAEC for objective or subjective signs of irritation after taking account of personality factors was 0.5 ppm or 0.3 ppm + peaks of 0.6 ppm in the Lang-study. A further refinement of the NOAEC was achieved by Mueller et al., (2010) by using intermediate and higher exposure concentrations. Thereby a NOAEC of 0.7 ppm or 0.4 ppm + peaks of 0.8 ppm was defined.
Based on the MAK value and taking into consideration the most recent study by Mueller et al., (2010) a DNEL of 0.4 ppm is considered appropriate to protect against irritation and thereby also against carcinogenicity in humans after inhalation exposure.
Formaldehyde Worker-DNEL long-term for inhalation route-local: 0.4 ppm
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.9 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):
- 150
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 434.8 mg/m³
- Explanation for the modification of the dose descriptor starting point:
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) is considered to be 1.15 m³/kg bw. Therefore, the modified dose descriptor starting point is 434.8 mg/m3 (= 1000 / 2 / 1.15).
- AF for differences in duration of exposure:
- 6
- Justification:
- Extrapolation to chronic exposure based on a sub-acute toxicity study
- AF for other interspecies differences:
- 2.5
- Justification:
- For inhalation studies only a factor 2.5 is used, and no correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animals and humans breathe at a rate depending on their caloric requirements.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor for consumers
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 16.67 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):
- 600
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on the low Log Kow and the very high water solubility, dermal absorption is expected to be low. A ratio of 0.1 for oral to dermal absorption is therefore provisionally suggested for DNEL derivation.
- AF for differences in duration of exposure:
- 6
- Justification:
- Extrapolation to chronic exposure based on a sub-acute toxicity study.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor for allometric scaling.
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factor for allometric scaling.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment for consumers.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
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:
- 1.67 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):
- 600
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route-to-route extrapolation is required as it is oral route.
- AF for differences in duration of exposure:
- 6
- Justification:
- Extrapolation to chronic exposure based on a sub-acute toxicity study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor for allometric scaling.
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor for consumers.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
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.
Short-term toxicity
According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure. The substance is also not classified as irritating or sensitizing to the skin and therefore no derivation of the DNEL for local dermal effects needs to be derived. No data is available whether the test substance could cause irritation to the respiratory tract and therefore no DNEL could be derived.
Long-term toxicity
A subacute (28-days) oral toxicity study is available in rats. In none of the dosing groups treatment-related effects were observed on mortality, clinical signs, body weight, food consumption, ophthalmic examinations, clinical pathology investigations, organ weight, macroscopic and microscopic findings. Therefore, a NOAEL of 1000 mg/kg bw was determined. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. The low log Pow value and the high water solubility (>10000 mg/L) suggest that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for these substances will be low. In the absence of route-specific information a ratio of 0.1 for oral to dermal absorption is provisionally suggested for the risk assessment of the substance, based on its physical-chemical properties. Additionally, for the inhalation route of exposure, acute and long-term, local effects, the DNEL values from formaldehyde were taken into consideration. As worst-case scenario the registered substance contains a maximum of 2.5 % of formaldehyde, therefore, the corresponding DNEL value was modified by a factor 40.
DNEL acute local - inhalation
As regards the DNEL short-term inhalation for workers according to the Guidance on information requirements and chemical safety assessment, Chapter R.8; APPENDIX R. 8-13 (Deriving DNELs, when a community/national occupational exposure limit (OEL) is available) the registrant is allowed to use a national occupational exposure limit in place of developing a DNEL.
A national occupational exposure limit (MAK value) has been adopted. Toxicological information and evaluations of health effects used for setting the national OEL are documented and available (German MAK commission; Greim 2000). The study of Lang et al., 2008 reconfirms the MAK value of 0.3 ppm with a short-term excursion factor of 2 (STEL 0.6 ppm) as no objective signs for sensory irritation were found in volunteers exposed to 0.3 ppm with peaks of 0.6 ppm or at 0.5 ppm over 4 h. Recently Müller et al. (2010) defined the NOAEC in more detail. They did not observe objective or subjective signs of irritation at peak exposure concentrations of 0.8 ppm over 15 min and at 0.7 ppm over 4h. These NOAECs pertained likewise to persons with high and low sensitivity for sensory irritation as determined by CO2 threshold. In comparison to the findings of Lang et al. (2007) that peak exposures of 1 ppm lead to sensory irritation, this indicates that any irritation occurring in the range between 0.7 and 1 ppm will rapidly subside and that no irritation will occur at 15 min peaks of 0.8 ppm. Therefore, 0.8 ppm is taken as acute DNEL (15 min).
Formaldehyde DNEL short term inhalation worker exposure = STEL (15 minutes) of 0.8 ppm.
Worker-DNEL long-term for inhalation route-local
Derivation of the worker-DNEL long-term for inhalation route-local is driven by effects on the upper respiratory tract especially taking into consideration the development of nasal tumors in rats. According to the Guidance on information requirements and chemical safety assessment, Chapter R.8; APPENDIX R. 8-13 (Deriving DNELs, when a community/national occupational exposure limit (OEL) is available) the registrant can use a national occupational exposure limit in place of developing a DNEL.
A national occupational exposure limit (MAK value) has been adopted. Toxicological information and evaluations of health effects used for setting the national OEL are documented and available (German MAK commission; Greim 2000). The German MAK commission (2000) developed a detailed mode of action for the induction of nasal tumors in rats after inhalation exposure. For cytotoxicity, cell proliferation and nasal tumor development the NOAECs are in the range between 2 and 6 ppm, while for DNA protein cross link formation (DPX) a clear NOEL could not be established. Most importantly, the proliferation rate of the respiratory epithelium is very low and is not increased up to concentrations of 2 ppm. Therefore, the probability of fixation of DPX into permanent mutations is low considering the rapid repair of DPX. The commission concluded that the occurrence of tumors is the result of chronic proliferative processes and that the genotoxicity of formaldehyde plays no or at most a minor part in its carcinogenic potential. Under these considerations the MAK value for the workplace was set at 0.3 ppm with a factor of 2 for peak exposures of 15 min and a ceiling of 1 ppm. The avoidance of cell proliferation in the respiratory tract was decisive for defining the MAK value. Cell proliferation is caused by cytotoxic irritation of formaldehyde, but data on cytotoxic irritation of the respiratory tract are not available for humans. However, the database for sensory irritation to the eye, a more sensitive parameter, was considered sufficient for setting the MAK value at 0.3 ppm. The review of Paustenbach et al. (1997) was an important consideration of the German MAK commission for defining their MAK value of 0.3 ppm. But according to this review and the review of Arts et al., 2007 appreciable subjective symptoms will only be noted at or above 1 ppm. As all these studies reviewed only relied on subjective symptoms, much more weight has to be given to the more recent investigations of Lang et al. (2007) and Mueller et al. (2010) because the following important aspects were taken into consideration:
- objective signs of irritation, like eye blinking rate or conjunctival redness
- influence of personality factors
- confounding by odor (Lang-study)
- evaluation of subgroups with high and low sensitivity for nasal irritation (Mueller-study).
The NOAEC for objective or subjective signs of irritation after taking account of personality factors was 0.5 ppm or 0.3 ppm + peaks of 0.6 ppm in the Lang-study. A further refinement of the NOAEC was achieved by Mueller et al., (2010) by using intermediate and higher exposure concentrations. Thereby a NOAEC of 0.7 ppm or 0.4 ppm + peaks of 0.8 ppm was defined.
Based on the MAK value and taking into consideration the most recent study by Mueller et al., (2010) a DNEL of 0.4 ppm is considered appropriate to protect against irritation and thereby also against carcinogenicity in humans after inhalation exposure.
Formaldehyde Worker-DNEL long-term for inhalation route-local: 0.4 ppm
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) is considered to be 1.15 m³/kg bw. Therefore, the modified dose descriptor starting point is 434.8 m³/kg bw (= 1000 / 2 / 1.15).
A subacute (28-days) oral toxicity study is available in rats. In none of the dose groups treatment related effects were observed on mortality, clinical signs, body weight, food consumption, ophthalmic examinations, clinical pathology investigations, organ weight, macroscopic and microscopic findings. Therefore, a NOAEL of 1000 mg/kg bw was determined. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route.
An acute inhalation study has been performed, however, no effect has been seen on the highest tested concentration (4.83 mg/L air). Moreover, no significant inhalation exposure is expected. The long-term DNEL is normally sufficient to ensure that effects do not occur and to protect workers, if long term DNELs are maintained. Therefore, a DNEL does not need to be derived.
No data on inhalation toxicity after repeated exposure is available as the corresponding test was waved based on exposure considerations. No significant inhalation exposure is expected. As no studies are available on the local effects by inhalation, no DNEL could be derived. An acute inhalation study has been performed, however no effect has been seen on the highest tested concentration (4.83 mg/L). Moreover, no significant inhalation exposure is expected. Therefore, a DNEL does not need to be derived. Based on the low Log Kow and the very high water solubility, dermal absorption is expected to be low. A ratio of 0.1 for oral to dermal absorption is therefore provisionally suggested for DNEL derivation. A subacute (28-days) oral toxicity study is available in rats. In none of the dosing groups treatment-related effects were observed on mortality, clinical signs, body weight, food consumption, ophthalmic examinations, clinical pathology investigations, organ weight, macroscopic and microscopic findings. Therefore, a NOAEL of 1000 mg/kg bw was determined. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. The dermal exposure of rats to 2000 mg/kg bw did not cause any deaths or severe signs of toxicity in an OECD TG 402 and GLP compliant test. Accordingly, the substance does not need to be classified and a DNEL does not need to be derived. The long-term DNEL is normally sufficient to ensure that effects do not occur and to protect workers, if long term DNELs are maintained.
The test item is not irritant to the skin and is not a skin sensitizer based on a weight of evidence approach. Accordingly, the substance does not need to be classified and a DNEL does not need to be derived.
A subacute (28-days) oral toxicity study is available in rats. In none of the dosing groups treatment-related effects were observed on mortality, clinical signs, body weight, food consumption, ophthalmic examinations, clinical pathology investigations, organ weight, macroscopic and microscopic findings. Therefore, a NOAEL of 1000 mg/kg bw was determined. No route-to-route extrapolation is needed to derive the DNEL.
The oral exposure of rats to 2000 mg/kg bw DMPPA_701-402-5 did not cause any deaths or severe signs of toxicity in an OECD 401 and GLP compliant test. Accordingly, the substance does not need to be classified and a DNEL does not need to be derived. The long-term DNEL is normally sufficient to ensure that effects do not occur if long term DNELs are maintained. 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.
Short-term toxicity
According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. Since the substance is not classified for acute dermal, inhalation, and oral toxicity, no short-term DNELs needs to be derived for these routes of exposure. The substance is also not classified as irritating or sensitizing to the skin and therefore no derivation of the DNEL for local dermal effects needs to be derived. No data is available whether the test substance could cause irritation to the respiratory tract and therefore no DNEL could be derived.
Long-term toxicity
A subacute (28-days) oral toxicity study is available in rats. In none of the dose groups treatment related effects were observed on mortality, clinical signs, body weight, food consumption, ophthalmic examinations, clinical pathology investigations, organ weight, macroscopic and microscopic findings. Therefore, a NOAEL of 1000 mg/kg bw was determined. Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. The low log Pow value and the high water solubility (>10000 mg/L) suggest that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for these substances will be low. In the absence of route-specific information a ratio of 0.1 for oral to dermal absorption is provisionally suggested for the risk assessment of the substance, based on its physical-chemical properties.
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.