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EC number: 234-196-6 | CAS number: 10591-84-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.3 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
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 234 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There is no long term study available using the inhalation route. Thus, as starting point for the calculation, the LOAEL of the subacute oral gavage study has to be taken into account. Furthermore, there are no quantitative data on absorption rates for oral or inhalation route available. Vulkacit I has a molecular weight of 364.5 , the log Pow given in IUCLID is > 4 and it is nearly unsoluble in water. Moderate log P values (between (-1 and 4) are favorable for absorption directly across the respiratory tract epithelium by passive diffusion. Any lipophilic compound may be taken up by micellular solubilisation but this mechanism may be of particular importance for highly lipophilic compound (Log P >4) particular those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed. Therefore is can be assumed that inhalation absorption is in the same range as oral absorption and no further default value has to be introduced Furthermore, as required in the ECHA guidance document to extrapolate from LOAEC to NOAEC a factor of 3 has to be introduced. Overall: LOAEL: 100 mg/kg bw; body weight worker: 70 kg; air volume inhaled per shift: 10 m3; LOAEL -> NOAEL: factor of 3
- AF for dose response relationship:
- 1
- Justification:
- A factor of 3 is already applied in the NOAEC starting point derivation.
- AF for differences in duration of exposure:
- 2
- Justification:
- Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default rat-> human
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor REACH Guidance R8
- AF for intraspecies differences:
- 5
- Justification:
- default factor REACH Guidance R8
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
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
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:
- LOAEL
- Value:
- 100 mg/kg bw/day
- AF for dose response relationship:
- 3
- Justification:
- LOAEL -> NOAEL
- AF for differences in duration of exposure:
- 2
- Justification:
- Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default factor REACH Guidance R8
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor REACH Guidance R8
- AF for intraspecies differences:
- 5
- Justification:
- default factor REACH Guidance R8
- AF for the quality of the whole database:
- 1
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
Introductory Note
There is no sub chronic study available as required by Regulation (EC)1907/2006 (REACH) ANNEX IX section 8.6.2
There is a reliable short term toxicity study (28 days) which was performed according to OECD TG 407 and GLP available In this available 28-day gavage study with rats (0, 100, 300 and 1000 mg/kg bw/day given as suspension in Solutol 15 HS /Ethanol /water = 4 : 1 : 5, Wirnitzer 2013) N,N’-Dimethyldiphenylthiuram disulphide caused significant hemolytic anemia from 100 mg/kg bw/day (LOAEL) onwards increasing in severity with the dose accompanied by histopathological effects in spleen and kidney but not in the liver, discolored feces at mid and high dose rats (both sexes) and reduced body weight development in high dosed rats. Dose-related increasing significant reticulocytosis can be interpreted as adaptive process. A NOAEL was not established.
Based on the severe effects observed a 90-day oral study in rats according to OECD TG 408 and GLP is proposed.
In the mean time, until the results of the sub-chronic studies are available, it is considered important to provide a practical recommendation to the users of Vulkacit I and therefore to propose provisory DNELs (systemic, long term) for which the available subacute oral rat study will be considered. The procedure will be re-assessed as soon as the results of the planned repeated dose oral toxicity study are available
Furthermore, Vulkacit I is not irritating to the skin or mucous membranes. Therefore, no local DNELs will be derived.
Worker
There is no German or European Occupational Exposure Limit (OEL) available which could be used as starting point for derivation of systemic Worker- DNELs for Vulkacit I following dermal and inhalation route of exposure. DNEL for oral exposure has no relevance for the situation of workers.
DNEL (systemic, long term, dermal route)
There is no long term dermal study available. Therefore, the oral LOAEL has to be considered instead. According to ECHA Guidance Document, Chapter R8 Version 2, December 2010, no additional default factors have to be introduced when performing oral-to-dermal extrapolation because it can be assumed that dermal absorption will not be higher than oral absorption.
LOAEL (oral) = LOAEL (dermal) = 100 mg/kg bw/day
Assessment factors:
For LOAEL to NOAEL: 3
For exposure duration : subacute to chronic: 2
Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
For interspecies differences rat vs human: 4
For remaining interspecies differences: 2.5
For intraspecies differences worker 5
For reliablility of dose response: 1
For quality of the whole database: 1
Overall factor: 300
Thus, DNEL (systemic , long term, dermal route): 0.33 mg/kg bw/d
DNEL (systemic, short term, dermal route)
There is no short term study available which could be considered.
Therefore it is proposed for precaution purposes that the DNEL (systemic, long term, dermal route) can be taken as surrogate for the DNEL (systemic, short term, dermal route).
DNEL (systemic, long term inhalation route)
There is no long term study available using the inhalation route. Thus, as starting point for the calculation, the LOAEL of the subacute oral gavage study has to be taken into account. Furthermore, there are no quantitative data on absorption rates for oral or inhalation route available. Vulkacit I has a molecular weight of 364.5 , the log Pow given in IUCLID is > 4 and it is nearly unsoluble in water. Moderate log P values (between (-1 and 4) are favorable for absorption directly across the respiratory tract epithelium by passive diffusion. Any lipophilic compound may be taken up by micellular solubilisation but this mechanism may be of particular importance for highly lipophilic compound (Log P >4) particular those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed. Therefore is can be assumed that inhalation absorption is in the same range as oral absorption and no further default value has to be introduced
LOAEL (oral) = 100 mg/kg bw/day
For LOAEL to NOAEL 3
For extrapolation oral to inhalation 1
Respiratory volume worker 10 m³/ 8h
Body weight worker 70 kg
NOAEC (subacute, inhalation) 234 mg/m³ starting point
For exposure duration : subacute to chronic: 2
For interspecies differences rat vs human: 4
For remaining interspecies differences: 2.5
For intraspecies differences worker 5
For reliablility of dose response: 1
For quality of the whole database: 1
Overall factor: 100
Thus, the DNEL (long term, systemic, inhalation route) is 2.3 mg/m³
DNEL (systemic, short term, inhalation route)
The LC50 (rat) is > 5000 mg/m³/4h. In general, human is more susceptible for toxicological effects by inhalation exposure than rat. Therefore, and since there are no other data available using the inhalation route, it is proposed for precaution purposes that the DNEL (systemic, lomg term, inhalation route) can be taken as surrogate for the DNEL (systemic, short term, inhalation route).
Summary
The relevant DNELs for worker are:
DNEL (systemic, dermal route, long term and short term exposure): 0.33 mg/kg bw
DNEL (systemic, inhalation route, long term and short term exposure): 2.3 mg/m³
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.59 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):
- 200
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 117 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There is no long term study available using the inhalation route. Thus, as starting point for the calculation, the LOAEL of the subacute oral gavage study has to be taken into account. Furthermore, there are no quantitative data on absorption rates for oral or inhalation route available. Vulkacit I has a molecular weight of 364.5 , the log Pow given in IUCLID is > 4 and it is nearly unsoluble in water. Moderate log P values (between (-1 and 4) are favorable for absorption directly across the respiratory tract epithelium by passive diffusion. Any lipophilic compound may be taken up by micellular solubilisation but this mechanism may be of particular importance for highly lipophilic compound (Log P >4) particular those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed. Therefore is can be assumed that inhalation absorption is in the same range as oral absorption and no further default value has to be introduced Furthermore, as required in the ECHA guidance document to extrapolate from LOAEC to NOAEC a factor of 3 has to be introduced. Overall: LOAEL: 100 mg/kg bw; body weight worker: 70 kg; air volume inhaled per day: 20 m3; LOAEL -> NOAEL: factor of 3
- AF for dose response relationship:
- 1
- Justification:
- A factor of 3 is already applied in the NOAEC starting point derivation.
- AF for differences in duration of exposure:
- 2
- Justification:
- Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default factor REACH Guidance R8
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor REACH Guidance R8
- AF for intraspecies differences:
- 10
- Justification:
- default factor REACH Guidance R8
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Route of original study:
- Oral
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:
- 0.17 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:
- LOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- There is no long term dermal study available. Therefore, the oral LOAEL has to be considered for derivation of the DNEL (oral) as well as for The DNEL (dermal route). According to ECHA Guidance Document, Chapter R8 Version 2, December 2010, no additional default factors have to be introduced when performing oral-to-dermal extrapolation because it can be assumed that dermal absorption will not be higher than oral absorption. Furthermore, as required in the ECHA guidance document to extrapolate from LOAEL to NOAEL a factor of 3 has to be introduced
- AF for dose response relationship:
- 3
- Justification:
- LOAEL -> NOAEL
- AF for differences in duration of exposure:
- 2
- Justification:
- Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default factor REACH Guidance R8
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor REACH Guidance R8
- AF for intraspecies differences:
- 10
- Justification:
- default factor REACH Guidance R8
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
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:
- 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:
- LOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation has to be performed.
- AF for dose response relationship:
- 3
- Justification:
- LOAEL -> NOAEL
- AF for differences in duration of exposure:
- 2
- Justification:
- Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default factor REACH Guidance R8
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor REACH Guidance R8
- AF for intraspecies differences:
- 10
- Justification:
- default factor REACH Guidance R8
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
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
There is no sub chronic study available. as required by Regulation (EC)1907/2006 (REACH) ANNEX IX section 8.6.2
There is a reliable short term toxicity study (28 days) which was performed according to OECD TG 407 and GLP available In this available 28-day gavage study with rats (0, 100, 300 and 1000 mg/kg bw/day given as suspension in Solutol 15 HS /Ethanol /water = 4 : 1 : 5, Wirnitzer 2013) N,N’-Dimethyldiphenylthiuram disulphide caused significant hemolytic anemia from 100 mg/kg bw/day (LOAEL) onwards increasing in severity with the dose accompanied by histopathological effects in spleen and kidney but not in the liver, discolored feces at mid and high dose rats (both sexes) and reduced body weight development in high dosed rats. Dose-related increasing significant reticulocytosis can be interpreted as adaptive process. A NOAEL was not established.
Based on the severe effects observed a 90-day oral study in rats according to OECD TG 408 and GLP is proposed.
In the mean time, until the results of the sub-chronic studies are available, it is considered important to provide a practical recommendation to the users of Vulkacit I and therefore to propose provisory DNELs (systemic, long term) for which the available subacute oral rat study will be considered. The procedure will be re-assessed as soon as the results of the planned repeated dose oral toxicity study are available
Furthermore, Vulkacit I is not irritating to the skin or mucous membranes. Therefore, no local DNELs will be derived.
General public
DNEL (systemic, long term, oral route and dermal route)
There is no long term dermal study available. Therefore, the oral LOAEL has to be considered for derivation of the DNEL (oral) as well as for the DNEL (dermal route). According to ECHA Guidance Document, Chapter R8 Version 2, December 2010, no additional default factors have to be introduced when performing oral-to-dermal extrapolation because it can be assumed that dermal absorption will not be higher than oral absorption.
LOAEL (oral) = LOAEL (dermal) = 100 mg/kg bw/day
For LOAEL to NOAEL 3
NOAEL( subacute, oral route and dermal route): 33 mg/kg bw/day starting point
For exposure duration : subacute to chronic: 2
Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
For interspecies differences rat vs human: 4
For remaining interspecies differences: 2.5
For intraspecies differences (general public) 10
For reliablility of dose response: 1
For quality of the whole database: 1
Overall factor: 200
Thus, DNEL (systemic , long term, oral route): 0.17 mg/kg bw/d
Thus, DNEL (systemic, long term, dermal route): 0.17 mg/kg bw/d
DNEL (systemic, short term, oral route and dermal route)
The LD50 (oral is > 5000 mg/kg bw and no mortality and no clinical signs of intoxication were observed. Therefore is is proposed for precaution purposes that the DNEL(systemic , long term, oral route can be taken as surrogate for the DNEL (systemic, short term, oral route). as the considerations for the long term dermal DNEL apply also for the respective short term DNEL is is proposed that also the DNEL (systemic, long term, dermal route) can be taken as surrogate for the DNEL (systemic, short term, dermal route)
DNEL (systemic, long term inhalation route)
There is no long term study available using the inhalation route. Thus, as starting point for the calculation, the LOAEL of the subacute oral gavage study has to be taken into account. Furthermore, there are no quantitative data on absorption rates for oral or inhalation route available. Vulkacit I has a molecular weight of 364.5 , the log Pow given in IUCLID, is > 4 and it is nearly unsoluble in water. Moderate log P values (between (-1 and 4) are favorable for absorption directly across the respiratory tract epithelium by passive diffusion. Any lipophilic compound may be taken up by micellular solubilisation but this mechanism may be of particular importance for highly lipophilic compound (Log P >4) particular those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed. Therefore is can be assumed that inhalation absorption is in the same range as oral absorption and no further default value has to be introduced
LOAEL (oral) = 100 mg/kg bw/day
Corrected inhalatory LOAC= oraler LOAEL x 70 : 20
For LOAEC to NOAEC 3
NOAEC (subacute): 117 mg/m³ startring point
For exposure duration : subacute to chronic: 2
Hemolytic anemia with accompanied by histopathological effects in spleen and kidney are observed at all doses tested in the sub-acute toxicity study. Hemolytic anemia that accompany methaemoglobinaemia or haemolysis is considered to be an acute effect (e.g. see The MAK-Collection Part I: MAK Value Documentations, Aniline, Vol. 26. DFG, 2011). Since there are fundamental physiological differences between rats and humans and disorders observed in humans that accompany methaemoglobinaemia or haemolysis, is not expected that these effects occur in human spleens. Based on the effects observed a test proposal is included in the dossier for a 90-day oral study in rats according to OECD TG 408. In the meantime a provisional DNEL is calculated taking into account a time extrapolation factor of 2. This factor will be reconsidered once the data from the 90 day study become available.
For interspecies differences rat vs human: 4
For remaining interspecies differences: 2.5
For intraspecies differences genral public 10
For reliablility of dose response: 1
For quality of the whole database: 1
Overall factor: 200
Thus the DNEL (systemic, long term, inhalation route) is 0.59 mg/m³
DNEL (systemic, short term, inhalation route)
The LC50 (rat) is > 5000 mg/m³/4h. It is proposed for precaution purposes that the DNEL (systemic, long term, inhalation route) can be taken as surrogate for the DNEL (systemic, short term, inhalation route).
Summary
The relevant DNELs for general public are:
DNEL (systemic, oral route, long term and short term exposure): 0.17 mg/kg bw
DNEL (systemic, dermal route, long term and short term exposure): 0.17 mg/kg bw
DNEL (systemic, inhalation route, long term and short term exposure): 0.59 mg/m³
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.