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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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EC number: 224-167-6 | CAS number: 4221-98-1
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- 1.85 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:
- 75 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 92.566 mg/m³
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 4
- Justification:
- As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
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
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.625 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:
- 75 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 525 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure. Based on physicochemical data dermal absorption is possible but limited. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance”, the log Pow of >5 lies above the optimal range between -1 and 4. The molecular weight of the substance is above 100 g/mol, also limiting uptake through skin. Due to the low water solubility of <1 mg/L the substance is not sufficiently soluble to partition from the stratum corneum into the epidermis and therefore, according to the above mentioned guidance document, dermal uptake is likely to be low. Taken together, penetration through skin is anticipated to be less extensive than oral absorption and an absorption rate of 10 % of oral absorption was taken for calculation.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 4
- Justification:
- As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
General
DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.
Workers – Hazard via inhalation route
Long term systemic inhalation DNEL, worker
The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study.
Step 1: Selection of the relevant dose descriptor (starting point):
The combined repeated dose oral toxicity study OECD 422 is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral systemic NOAEL is 75 mg/kg bw/day.
Step 2: Modification into a correct starting point:
Using a conservative approach, a worker DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.
Relevant dose descriptor (NOAEL): 75 mg/kg bw/day
Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d
Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5
Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³
Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³
Frequency of exposure in study: 7 days/week
Frequency of worker exposure: 5 days/week
Corrected inhalatory NOAEC for workers
= 75 mg/kg bw/day* 0.5 * (1 / 0.38 m³/kg bw/day) * (6.7 m³/10 m³) * (7/5)
= 92.566 mg/m³
Step 3: Use of assessment factors: 50
Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 4
Remaining uncertainties AF: 1
In conclusion, long term systemic inhalation DNEL, workers = 1.85 mg/m3
Short term systemic inhalation DNEL, worker
No data for the classification and labelling of the test substance for acute systemic toxicity (inhalation) is available. The substance is not classified for acute oral toxicity and acute dermal toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.
Short and long term local inhalation DNEL, worker
No data on respiratory irritation is available. However, the test substance is not classified for eye irritation according to Regulation (EC) No 1272/2008 (CLP). This implies that no potential damage to mucosal tissue may occur by an inhalation exposure.
Workers – Hazard via dermal route
Long term systemic dermal DNEL, worker
The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study (OECD 422).
Step 1: Selection of the relevant dose descriptor (starting point):
The combined repeated dose toxicity study (OECD 422) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 75 mg/kg bw/day.
Step 2: Modification of the starting point:
There are no relevant experimental data on repeated dermal exposure. Based on physicochemical data dermal absorption is possible but limited. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance”, the log Pow of >5 lies above the optimal range between -1 and 4. The molecular weight of the substance is above 100 g/mol, also limiting uptake through skin. Due to the low water solubility of <1 mg/L the substance is not sufficiently soluble to partition from the stratum corneum into the epidermis and therefore, according to the above mentioned guidance document, dermal uptake is likely to be low. Taken together, penetration through skin is anticipated to be less extensive than oral absorption and an absorption rate of 10 % of oral absorption was taken for calculation.
Relevant dose descriptor (NOAEL): 75 mg/kg bw/day
Frequency of exposure in study: 7 days/week
Frequency of worker exposure: 5 days/week
Oral absorption of the rat / dermal absorption of humans (ABSoral-rat / ABSdermal-human): 50/10
Corrected dermal NOAEL for workers
75 mg/kg bw/day * (50%/10%) * (7/5) = 525 mg/kg bw/day
Step 3: Use of assessment factors: 200
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 4
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, workers = 2.625 mg/kg bw/day
Short term systemic dermal DNEL, worker
The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
Long term and short term local dermal DNEL, worker
The test item is classified for skin sensitization into Cat 1B according to Regulation (EC) No 1272/2008 (CLP). Thus, it is allocated to the moderate hazard band and a qualitative risk assessment has to be conducted (according to " Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation", May 2016).
Worker – Hazard for the eyes
The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP). Thus, no qualitative risk assessment is required.
References
(not included as endpoint study record)
- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.
- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.
- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.
- ECHA (2016). Guidance on information requirements and chemical safety assessment.Part E: Risk Characterisation, Version 3.0, May 2016.
- ECHA (2017). Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance, June 2017.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.278 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):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 75 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 27.78 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Using a conservative approach, a general population DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 4
- Justification:
- As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively homogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
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:
- 0.938 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):
- 400
- Dose descriptor starting point:
- NOAEL
- Value:
- 75 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 375 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure. Based on physicochemical data dermal absorption is possible but limited. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance”, the log Pow of >5 lies above the optimal range between -1 and 4. The molecular weight of the substance is above 100 g/mol, also limiting uptake through skin. Due to the low water solubility of <1 mg/L the substance is not sufficiently soluble to partition from the stratum corneum into the epidermis and therefore, according to the above mentioned guidance document, dermal uptake is likely to be low. Taken together, penetration through skin is anticipated to be less extensive than oral absorption and an absorption rate of 10 % of oral absorption was taken for calculation.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 4
- Justification:
- As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively homogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.018 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):
- 400
- Dose descriptor starting point:
- NOAEL
- Value:
- 75 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 75 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No modification is used as the same exposure route is considered.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 4
- Justification:
- As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively homogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
General
DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.
General population – Hazard via inhalation route
Long term systemic inhalation DNEL, general population
The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study.
Step 1: Selection of the relevant dose descriptor (starting point):
The combined repeated dose oral toxicity study OECD 422 is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral systemic NOAEL is 75 mg/kg bw/day.
Step 2: Modification into a correct starting point:
Using a conservative approach, a general population DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.
Relevant dose descriptor (NOAEL): 75 mg/kg bw/day
Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.35 m³/kg bw/d
Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5
Frequency of exposure in study: 7 days/week
Frequency of general population exposure: 7 days/week
Corrected inhalatory NOAEC for workers
= 75 mg/kg bw/day* 0.5 * (1 / 1.35 m³/kg bw/day) * (7/7)
= 27.78 mg/m³
Step 3: Use of assessment factors: 100
Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 4
Remaining uncertainties AF: 1
In conclusion, long term systemic inhalation DNEL, general population = 0.278 mg/m3
Short term systemic inhalation DNEL, general population
No data for the classification and labelling of the test substance for acute systemic toxicity (inhalation) is available. The substance is not classified for acute oral toxicity and acute dermal toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.
Short and long term local inhalation DNEL, general population
No data on respiratory irritation is available. However, the test substance is not classified for skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP). This implies that no potential damage to mucosal tissue may occur by an inhalation exposure.
General population – Hazard via dermal route
Long term systemic dermal DNEL, general population
The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study (OECD 422).
Step 1: Selection of the relevant dose descriptor (starting point):
The combined repeated dose toxicity study (OECD 422) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 75 mg/kg bw/day.
Step 2: Modification of the starting point:
There are no relevant experimental data on repeated dermal exposure. Based on physicochemical data dermal absorption is possible but limited. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance”, the log Pow of >5 lies above the optimal range between -1 and 4. The molecular weight of the substance is above 100 g/mol, also limiting uptake through skin. Due to the low water solubility of <1 mg/L the substance is not sufficiently soluble to partition from the stratum corneum into the epidermis and therefore, according to the above mentioned guidance document, dermal uptake is likely to be low. Taken together, penetration through skin is anticipated to be less extensive than oral absorption and an absorption rate of 10 % of oral absorption was taken for calculation.
Relevant dose descriptor (NOAEL): 75 mg/kg bw/day
Frequency of exposure in study: 7 days/week
Frequency of general population exposure: 7 days/week
Oral absorption of the rat / dermal absorption of humans (ABSoral-rat / ABSdermal-human): 50/10
Corrected dermal NOAEL for general population
75 mg/kg bw/day * (50%/10%) * (7/7) = 375 mg/kg bw/day
Step 3: Use of assessment factors: 400
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 10
Exposure duration AF: 4
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, general population = 0.9375 mg/kg bw/day
Short term systemic dermal DNEL, general population
The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
Long term and short term local dermal DNEL, general population
The test item is classified for skin sensitization into Cat 1B according to Regulation (EC) No 1272/2008 (CLP). Thus, it is allocated to the moderate hazard band and a qualitative risk assessment has to be conducted (according to " Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation", May 2016).
General population – Hazard via oral route
Long term systemic oral DNEL, general population
The DNEL long term, systemic (oral) is derived from the combined repeated dose oral toxicity study (OECD 422).
Step 1: Selection of the relevant dose descriptor (starting point):
The combined repeated dose toxicity study (OECD 422) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 75 mg/kg bw/day.
Step 2: Modification of the starting point:
No modification is used as the same exposure route is considered.
Step 3: Use of assessment factors: 400
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 4
Remaining uncertainties AF: 1
In conclusion, long term systemic oral DNEL, general population = 0.01875 mg/kg bw/day
Short term systemic oral DNEL, General population
The test item is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
General population – Hazard for the eyes
The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP). Thus, no qualitative risk assessment is required.
References
(not included as endpoint study record)
- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.
- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.
- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.
- ECHA (2016). Guidance on information requirements and chemical safety assessment.Part E: Risk Characterisation, Version 3.0, May 2016.
- ECHA (2017). Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance, June 2017.
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.
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