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EC number: 208-857-4 | CAS number: 544-01-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.2 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:
- 88.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not for concentrations
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor for remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- for worker
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 270 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 3 377 mg/m³
- AF for dose response relationship:
- 1
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
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:
- 0.33 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:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
8 h exposure time, no dermal study available
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor for remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- for worker
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
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
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. The substance is classified for acute inhalation toxicity. For short term exposure to diisopentyl ether, a DNEL has been derived based on the results of an acute inhalation study according to the REACH guidance.
Assessment of short term exposure is not considered relevant, when 8 hour exposure levels remain under the chronic-DNEL. The short term DNEL for diisopentyl ether is high (270 mg/m3, about 225 times higher) relative to the chronic DNEL for diisopentyl ether.
The relationship between determinants of acute and full shift exposure distributions have been calculated (Kumagai and Matsunaga, 1994). In general, the 95th percentile of 15 minute exposure data is about twice the 90th percentile and 4 times the 75th percentile of full shift data collected for the same situation. Even in a worst case situation when:
- the full shift measurement data reflects the 75th percentile,
- there is a high variability within the short term data,
- the 99th percentile of the short term value is required,
the factor by which to multiply the 8 hour value to get to the short term value is 40. This is still much lower than 225. This means that when 8 hour exposures remain under the chronic DNEL for diisopentyl ether, the 15 minute exposure levels will always be safe.
The substance is not classified as irritating to the skin or eyes. Based on the results of a LLNA assay, diisopentyl ether is proposed to be classified as skin sensitizing substance. However, it is not possible to derive a DNEL based on the available data. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent dermal exposure that will cause skin sensitisation. 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
The key study for DNEL derivation was identified as a recent repeated dose oral study.according to OECD 422 (De Raaf-Beekhuijzen, 2012) where a NOAEL of 100 mg/kg bw/day was derived. The reason for selecting this study is that the design includes both the OECD 407 and OECD 421 guidelines requirements and the exposure duration included an additional 2 weeks exposure duration when compared to a standard 4 weeks toxicity study. The DNELs for chronic systemic toxicity for the inhalation and dermal route are derived via route-to-route extrapolation based on the repeated dose oral toxicity study.
In the absence of substance specific quantitative data on absorption, 100% absorption is assumed for the inhalation and 50% for the oral route. Based on the absence of dermal absorption data, it is assumed that the dermal bioavailability is equal to oral bioavailability (worst case scenario).
Worker DNELs
Long-term inhalation, systemic effects
As inhalation repeated dose toxicity studies with diisopentyl ether are not available, route to route extrapolation was applied to derive a DNEL for the inhalation route, based on the results of a recent oral OECD 422 study in rat (De Raaf-Beekhuijzen, 2012) where an NOAEL of 100 mg/kg bw/day was derived.
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 100 mg/kg bw/day |
Exposure of rats at concentrations up to 1000 mg/kg bw/day did not induce clinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the increased liver weights (mid and high dose females and high dose males) and treatment-related microscopic findings in thyroid (males), thymus (males) and liver (both sexes), a dose of 100 mg/kg bw/day was considered as NOAEL |
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 |
100 / 2 / 0.38 x (6.7/10) = 88.2 mg/m3 |
|
Step 3) Assessment factors |
|
|
Interspecies |
2.5 |
No factor for allometric scaling is needed in case of inhalation exposure.A default factor of 2.5 for remaining uncertainties is used. |
Intraspecies |
5 |
Default AF for workers |
Exposure duration |
6 |
Extrapolation to chronic exposure based on a sub-acute toxicity study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
88.2 / (2.5 x 5 x 6 x 1 x 1) = 1.18 mg/m3 |
Short-term – inhalation, systemic effects
Approach according to REACH guidance
Based on the available acute inhalation toxicity study in rats (Van Huygevoort, 2012).
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 2000 mg/m3 |
No deaths occurred and no abnormalities were found at macroscopic examination. Therefore, 2000 mg/m3 is interpreted as a NOAEC. |
Step 2) Modification of starting point |
3√(20003x 16)
6.7/10 |
In the REACH guidance (R.8, Appendix R. 8-8), it is mentioned: ‘If a DNEL for acute toxicity needs to be established, this should be derived only for a specified fraction of the daily exposure duration (usually 15 minutes)’. The most appropriate approach is the modified Haber’s law (Cn* t = k). For extrapolation from longer to shorter durations a default value of n=3 should be used.
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3). |
Step 3) Assessment factors |
|
|
Interspecies |
2.5 |
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. |
Intraspecies |
5 |
Default AF for workers |
Exposure duration |
1 |
|
Dose response |
1 |
|
Quality of database |
1 |
|
Step 4) Calculate DNEL |
3√(20003x 16) x (6.7/10)/ (2.5 x 5 x 1 x 1 x 1) = 270 mg/m3 |
Long-term dermal, systemic effects
As dermal repeated dose toxicity studies with diisopentyl ether are not available, route to route extrapolation was applied to derive a DNEL for the dermal route, based on the resuls of a recent oral OECD 422 study in rat (De Raaf-Beekhuijzen, 2012) where an NOAEL of 100 mg/kg bw/day was derived.
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 100 mg/kg bw/day |
Exposure of rats at concentrations up to 1000 mg/kg bw/day did not induceclinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the increased liver weights (mid and high dose females and high dose males) and treatment-related microscopic findings in thyroid (males), thymus (males) and liver (both sexes), a dose of 100 mg/kg bw/day was considered as NOAEL |
Step 2) Modification of starting point |
1 |
Based on the absence of skin absorption data, it is assumed that the dermal bioavailability is equal to the oral bioavailability |
Modified dose-descriptor |
100 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 x 2.5 |
Assessment factor for allometric scaling and remaining uncertainties. |
Intraspecies |
5 |
Default AF for workers |
Exposure duration |
6 |
Extrapolation to chronic exposure based on a sub-acute toxicity study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
100 / (4 x 2.5 x 5 x 6 x 1 x 1) = 0.33 mg/kg bw/day |
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.29 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:
- 43.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
24 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not required for concentration
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor for remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 202 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 5 040 mg/m³
- AF for dose response relationship:
- 1
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.17 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:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
24 h exposure time, no dermal study available
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- extrapolation rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
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)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.17 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:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation performed
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- extrapolation rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
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. The substance is classified for acute inhalation toxicity. For short term exposure to diisopentyl ether, a DNEL has been derived based on the results of an acute inhalation study according to the REACH guidance.
The substance is not classified as irritating to the skin or eyes. Based on the results of a LLNA assay, diisopentyl ether is proposed to be classified as skin sensitizing substance. However, it is not possible to derive a DNEL based on the available data. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent dermal exposure that will cause skin sensitisation. 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
The key study for DNEL derivation was identified as a recent repeated dose oral study.according to OECD 422 (De Raaf-Beekhuijzen, 2012) where a NOAEL of 100 mg/kg bw/day was derived. The reason for selecting this study is that the design includes both the OECD 407 and OECD 421 guidelines requirements and the exposure duration included an additional 2 weeks exposure duration when compared to a standard 4 weeks toxicity study. The DNELs for chronic systemic toxicity for the inhalation and dermal route are derived via route-to-route extrapolation based on the repeated dose oral toxicity study.
In the absence of substance specific quantitative data on absorption, 100% absorption is assumed for the inhalation and 50% for the oral route.
Based on the absence of dermal absorption data, it is assumed that the dermal bioavailability is equal to oral bioavailability (worst case scenario).
General population DNELs
Long-term inhalation, systemic effects
As inhalation repeated dose toxicity studies with diisopentyl ether are not available, route to route extrapolation was applied to derive a DNEL for the inhalation route, based on the results of a recent oral OECD 422 study in rat (De Raaf-Beekhuijzen, 2012) where an NOAEL of 100 mg/kg bw/day was derived
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 100 mg/kg bw/day |
Exposure of rats at concentrations up to 1000 mg/kg bw/day did not induceclinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the increased liver weights (mid and high dose females and high dose males) and treatment-related microscopic findings in thyroid (males), thymus (males) and liver (both sexes), a dose of 100 mg/kg bw/day was considered as NOAEL |
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 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2). |
Modified dose-descriptor |
100 / 2 / 1.15 = 43.5 mg/m3 |
|
Step 3) Assessment factors |
|
|
Interspecies |
2.5 |
No factor for allometric scaling is needed in case of inhalation exposure.A default factor of 2.5 for remaining uncertainties is used. |
Intraspecies |
10 |
Default AF for general population |
Exposure duration |
6 |
Extrapolation to chronic exposure based on a sub-acute toxicity study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
43.5 / (2.5 x 10 x 6 x 1 x 1) = 0.29 mg/m3 |
Short-term – inhalation, systemic effects
Approach according to REACH guidance
Based on the available acute inhalation toxicity study in rats (Van Huygevoort, 2012).
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEC: 2000 mg/m3 |
No deaths occurred and no abnormalities were found at macroscopic examination. Therefore, 2000 mg/m3is interpreted as a NOAEC. |
Step 2) Modification of starting point |
3√(20003x 16)
|
In the REACH guidance (R.8, Appendix R. 8-8), it is mentioned: ‘If a DNEL for acute toxicity needs to be established, this should be derived only for a specified fraction of the daily exposure duration (usually 15 minutes)’. The most appropriate approach is the modified Haber’s law (Cn* t = k). For extrapolation from longer to shorter durations a default value of n=3 should be used. |
Step 3) Assessment factors |
|
|
Interspecies |
2.5 |
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. |
Intraspecies |
10 |
Default AF for general population |
Exposure duration |
1 |
|
Dose response |
1 |
|
Quality of database |
1 |
|
Step 4) Calculate DNEL |
3√(20003x 16) / (2.5 x 10 x 1 x 1 x 1) = 202 mg/m3 |
Long-term dermal, systemic effects
As dermal repeated dose toxicity studies with diisopentyl ether are not available, route to route extrapolation was applied to derive a DNEL for the dermal route, based on the results of a recent oral OECD 422 study in rat (De Raaf-Beekhuijzen, 2012) where an NOAEL of 100 mg/kg bw/day was derived.
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 100 mg/kg bw/day |
Exposure of rats at concentrations up to 1000 mg/kg bw/day did not induceclinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the increased liver weights (mid and high dose females and high dose males) and treatment-related microscopic findings in thyroid (males), thymus (males) and liver (both sexes), a dose of 100 mg/kg bw/day was considered as NOAEL |
Step 2) Modification of starting point |
1 |
Based on the absence of skin absorption data, it is assumed that the dermal bioavailability is equal to the oral bioavailability |
Modified dose-descriptor |
100 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 x 2.5 |
Assessment factor for allometric scaling and remaining uncertainties. |
Intraspecies |
10 |
Default AF for workers |
Exposure duration |
6 |
Extrapolation to chronic exposure based on a sub-acute toxicity study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
100 / (4 x 2.5 x 10 x 6 x 1 x 1) = 0.17 mg/kg bw/day |
Long-term – oral, systemic effects
The key study for DNEL derivation was identified as the recent oral OECD 422 study in rat (De Raaf-Beekhuijzen, 2012) where an NOAEL of 100 mg/kg bw/day was derived.
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 100 mg/kg bw/day |
Exposure of rats at concentrations up to 1000 mg/kg bw/day did not induceclinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the increased liver weights (mid and high dose females and high dose males) and treatment-related microscopic findings in thyroid (males), thymus (males) and liver (both sexes), a dose of 100 mg/kg bw/day was considered as NOAEL |
Step 2) Modification of starting point |
1 |
No route to route extrapolation performed. |
Modified dose-descriptor |
100 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 x 2.5 |
Assessment factor for allometric scaling and remaining uncertainties. |
Intraspecies |
10 |
Default AF for workers |
Exposure duration |
6 |
Extrapolation to chronic exposure based on a sub-acute toxicity study |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
100 / (4 x 2.5 x 10 x 6 x 1 x 1) = 0.17 mg/kg bw/day |
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