Registration Dossier
Registration Dossier
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EC number: - | 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:
- 10.6 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):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 264 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Extrapolation from oral to inhalation exposure using route-to-route strategy described in Appendix R.8-2 of R.8 guidance
- AF for dose response relationship:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for differences in duration of exposure:
- 2
- Justification:
- Default value proposed in ECHA R.8 guidance for sub chronic to chronic exposure ( table R 8.6)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling for inhalation studies (Appendix R8.2)
- AF for intraspecies differences:
- 5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for the quality of the whole database:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
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:
- 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):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Extrapolation from oral to dermal exposure using route-to-route strategy described in Appendix R.8-2 of R.8 guidance
- AF for dose response relationship:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for differences in duration of exposure:
- 2
- Justification:
- Default value proposed in ECHA R.8 guidance for sub chronic to chronic exposure ( table R 8.6)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.3)
- AF for intraspecies differences:
- 5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for the quality of the whole database:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
1. Acute/short-term exposure-systemic effects:
Cutaneous route
In the key study (Tuffnell, 1992) no mortality and no local changes were noted at a limit dose of 2000 mg/kg. The dermal LD50 is therefore greater than 2000 mg/kg and ITC 288/S is not classified as hazardous via the dermal route.
No short-term systemic DNEL needs to be derived for cutaneous exposure, (ECHA guidance document R8.1.2.5)
Inhalation route
No data are available for acute short term exposure via this route of administration.
No DNEL could be calculated. However, the Occupational Exposure limits for the inhalable airborne fraction (particles < 100 µm) of 10 mg/m3 which is applied in many countries can be considered as a worst-case since the ITC288/S median particle size is between 106 and 150 µm and the possibility to have the inhalable fraction in the respiratory tractus is very low.
2. Acute/short-term exposure-local effects:
Cutaneous route
ITC 288/S was classified in category 1, H317 ( May cause an allergic skin reaction) according to the CLP regulation (1272/2008) and as a sensitiser to guinea pig skin (Xi, R43) according to the Directive 67/548/EEC based on the sensititisation study conducted according to the Guinea-Pig Maximisation test (see section 7.4).
Considering these data, it is very difficult to derive a threshold and to set a DNEL. Hence, only qualitative assessment can be performed following the approach described in the dossier to define the risk management measures (RMMs) and operational conditions (OCs), (R8 -10, p125).Inhalation route
No data are available for acute short term exposure via this route of administration.
No DNEL could be calculated. However, the Occupational Exposure limits for the inhalable airborne fraction (particles < 100 µm) of 10 mg/m3 which is applied in many countries can be considered as a worst-case since the ITC288/S median particle size is between 106 and 150 µm and the possibility to have the inhalable fraction in the respiratory tractus is very low.
3. Long-term exposure-inhalation route:
3.1 Long-term exposure-inhalation route/Systemic effects
The long-term DNEL inhalation exposure for systemic effects cannot be derived from repeated dose toxicity study by inhalation since this study is not available. However, a route to route extrapolation can be realised from an oral repeated dose toxicity study (OECD 408), selected as a key study for repeated dose toxicity endpoint (Parr, 2014 - reliability 1). There was systemic toxicity identified at the maximal dose tested in the repeated dose study by the oral route,There was a dose-related decrease in body weights and body weight gains in males at all doses which reached statistical significance at 1000 mg/kg/day. At necropsy, test item-related lower mean body weights were noted in males treated at 1000 mg/kg/day. Macroscopic test item-related abnormal growth or irregular color of lower incisor teeth was observed in some males and females treated at 1000 mg/kg/day. The NOAEL /oral/rat = 300 mg/kg bw/day can be considered for a route to route extrapolation to derive a DNEL for inhalation route. The following Table indicates the inhalation DNEL for systemic toxicity calculation
Table 3.1/1 DNEL calculation for long-term exposure by inhalation:
Worker |
Systemic long-term DNEL |
Step a: determination of the critical dose |
|
Key study |
Parr (2014).OECD 408, tested doses: 0, 100, 300 and 1000 mg/kg b.w/day, (Kr: 1). |
Relevant dose descriptor |
NOAEL/oral/rat (males and females) = 300 mg/kg bw/day, ( a slight change in body weight, gross and microscopic findings in teeth) |
Etape b : Correct starting point-factor and route to route extrapolation |
|
NAEC Worker (8h) a factor of 2 is applied due to oral to inhalation absorption difference. |
NOAEL (rat)/0.38*6.7/10 / 2 = 264 mg/kg bw/d |
Step c : assessment factors |
|
Intraspeciesdifferences (worker) |
5
|
Duration extrapolation (sub-chronic to chronic) |
2 |
Remaining uncertainties |
2.5 |
Overall assessment factor |
50 |
DNEL Long-term by inhalation route proposed(mg/m3) |
10,6 |
The
inhalation DNEL long-term for systemic effects is = 10,6 mg/m3 for
workers.
3.2 Long-term exposure-inhalation route/local effects
The Occupational Exposure limits for the inhalable airborne fraction (particles < 100 µm) of 10 mg/m3 which is applied in many countries can be considered as a worst-case since the ITC288/S median particle size is between 106 and 150 µm and the possibility to have the inhalable fraction in the respiratory tractus is very low.
Conclusion:
ITC288/S is a white powder (median particle size between 106 and 150 µm) and is considered as very soluble in water based on
water solubility above 2333 g/L at 20°C. As recommended in the R.8.7.1, p 54, for significantly soluble dusts, if the derived DNEL for inhalation is above the general dust limit (10 mg/m3for the inhalable airborne fraction) might apply. Considering these data and in order to protect the workers, the general dust limit of 10 mg/m3for the inhalable airborne fraction (more conservative) was selected. This general dust limit covers the specific and non-specific effects of the substance.
4. Long-term exposure-dermal route:
4.1 Long-term exposure-systemic effects/dermal route:
No repeated dose toxicity by the dermal route is available. However, no evidence of systemic toxicity was observed in the acute dermal toxicity (Tuffnell, 1992). There was systemic toxicity identified at the maximal dose tested in the repeated dose study by the oral route,There was a dose-related decrease in body weights and body weight gains in males at all doses which reached statistical significance at 1000 mg/kg/day. At necropsy, test item-related lower mean body weights were noted in males treated at 1000 mg/kg/day. Macroscopic test item-related abnormal growth or irregular color of lower incisor teeth was observed in some males and females treated at 1000 mg/kg/day. The NOAEL /oral/rat = 300 mg/kg bw/day can be considered for a route to route extrapolation to derive a DNEL for dermal route. The following Table indicates the dermal DNEL for systemic toxicity calculation
Table 4.1/1 DNEL calculation for long-term exposure by dermal route:
Worker |
Systemic long-term DNEL |
Step a: determination of the critical dose |
|
Key study |
Parr (2014).OECD 408, tested doses: 0, 100, 300 and 1000 mg/kg b.w/day (Kr: 1). |
Relevant dose descriptor |
NOAEL/oral/rat (males and females) = 300 mg/kg bw/day (worst case),( a slight change in body weight, gross and microscopic findings in teeth )
|
Etape b : Correct starting point-factor and route to route extrapolation |
|
Dermal NAEL(corrected) |
NOAEL oral-rat/1 = 300 mg/kg bw/d (On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral to dermal extrapolation) |
Step c : assessment factors |
|
Interspecies differences : - allometric scaling for metabolic rate - remaining differences (toxicokinetics and toxicodynamics) |
4 (rat)
2.5 |
Intraspecies differences |
5 (worker)
|
Duration extrapolation
|
2 (sub-chronic to chronic extrapolation) |
Issues related to dose-response |
1 (NOAEL (worst case)) |
Quality of whole database |
1 |
Overall assessment factor |
100 |
DNEL Long-term by dermal route proposed(mg/kg bw/day) |
3 |
The Dermal DNEL long-term for systemic effects is 3 mg/kg bw/day in the worker. However, no long-term dermal exposure is expected at this high level based on the precautions taken to prevent skin sensitisation effects.
4.2 Long-term exposure-local effects/dermal route:
The sensititisation study was conducted according to the Guinea-Pig Maximisation test (see section 7.4) ans showed positive results for the ITC 288/S (classified as skin sensitizer in Cat.1, H317). Considering these data, it is very difficult to derive a threshold and to set a DNEL. Hence, only qualitative assessment can be performed following the approach described in the dossier to define the risk management measures (RMMs) and operational conditions (OCs), (R8 -10, p125).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.6 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
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 130 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Extrapolation from oral to inhalation exposure using route-to-route strategy described in Appendix R.8-2 of R.8 guidance
- AF for dose response relationship:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for differences in duration of exposure:
- 2
- Justification:
- Default value proposed in ECHA R.8 guidance for sub chronic to chronic exposure ( table R 8.6)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling for inhalation studies (Appendix R8.2)
- AF for intraspecies differences:
- 10
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for the quality of the whole database:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
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:
- 1.5 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
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Extrapolation from oral to dermal exposure using route-to-route strategy described in Appendix R.8-2 of R.8 guidance
- AF for dose response relationship:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for differences in duration of exposure:
- 2
- Justification:
- Default value proposed in ECHA R.8 guidance for sub chronic to chronic exposure ( table R 8.6)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.3)
- AF for intraspecies differences:
- 10
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for the quality of the whole database:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
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:
- 1.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route ro route extrapolation
- AF for dose response relationship:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for differences in duration of exposure:
- 2
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.3)
- AF for intraspecies differences:
- 10
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for the quality of the whole database:
- 1
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value proposed in ECHA R.8 guidance ( table R 8.6)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
1. Acute/short-term exposure-systemic effects:
Cutaneous route
In the key study (Tuffnell, 1992) no mortality and no local changes were noted at a limit dose of 2000 mg/kg. The dermal LD50 is therefore greater than 2000 mg/kg and ITC 288/S is not classified as hazardous via the dermal route.
No short-term systemic DNEL needs to be derived for cutaneous exposure, (ECHA guidance document R8.1.2.5)
Inhalation route
No data are available for this route of administration. However, the acute inhalation study does not need to be conducted as the substance is tested by two routes (oral + dermal), the LD50 oral (rat): > 5000 mg/kg bw and the LD50 dermal (rat): > 2000 mg/kg bw. These results leading to the conclusion that ITC 288/S is not toxic by acute exposure.
Oral route
In the key study (Tuffnell, 1992) no mortality, no signs of systemic toxicity and no abnormalities were noted at necropsy at a limit test of 5000 mg/kg bw. The oral LD50 combined of ITC 288/S was found to be greater than 5000 mg/kg bw, therefore it is not classified as hazardous via the oral route.
No short-term systemic DNEL needs to be derived for oral exposure, (ECHA guidance document R8.1.2.5)
2. Acute/short-term exposure-local effects:
Cutaneous route
ITC 288/S was classified in category 1, H317 ( May cause an allergic skin reaction) according to the CLP regulation (1272/2008) and as a sensitiser to guinea pig skin (Xi, R43) according to the Directive 67/548/EEC based on thesensititisation study conducted according to the Guinea-Pig Maximisation test (see section 7.4).
Considering these data, it is very difficult to derive a threshold and to set a DNEL. Hence, only qualitative assessment can be performed following the approach described in the dossier to define the risk management measures (RMMs) and operational conditions (OCs), (R8 -10, p125).
Inhalation route
General population exposure to ITC 288/S as a dust or in aerosol form is not anticipated. No short-term local DNEL needs to be derived for inhalation exposure.
3. Long-term exposure-inhalation route:
3.1 Long-term exposure-inhalation route/Systemic effects
The long-term DNEL inhalation exposure for systemic effects cannot be derived from repeated dose toxicity study by inhalation since this study is not available. However, a route to route extrapolation can be realised from an oral repeated dose toxicity study (OECD 408), selected as a key study for repeated dose toxicity endpoint (Parr, 2014 - reliability 1).
The NOAEL /oral/rat = 300 mg/kg bw/day can be selected as the relevant dose descriptor, therefore a route to route extrapolation can be made to derive a DNEL for inhalation route.The following Table indicates the inhalation DNEL for systemic toxicity calculation.
Table 3.1/1 DNEL calculation for long-term exposure by inhalation:
General population |
Systemic long-term DNEL |
Step a: determination of the critical dose |
|
Key study |
Parr (2014).OECD 408, tested doses: 0, 100, 300 and 1000 mg/kg b.w/day (Kr: 1). |
Relevant dose descriptor |
NOAEL/oral/rat (males and females) = 300 mg/kg bw/day, (a slight change in body weight, gross and microscopic findings in teeth at the highest tested dose) |
Etape b : Correct starting point-factor and route to route extrapolation |
|
NAEC human (24h) |
NOAEL(rat) /1.15 = 260 mg/ m3 |
Step c : assessment factors |
|
Intraspeciesdifferences (General population) |
10 |
Duration extrapolation (sub-chronic to chronic) |
2 |
Remaining uncertaintites |
5 |
Overall assessment factor |
100 |
DNEL Long-term by inhalation route proposed(mg/m3) |
2,6 |
The inhalation DNEL long-term for systemic effects is = 2.6 mg/m3in the general population. However, general population exposure to ITC 288/S as a dust or in aerosol form is not anticipated.
3.2 Long-term exposure-inhalation route/local effects
General population exposure to ITC 288/S as a dust or in aerosol form is not anticipated. No long-term local DNEL needs to be derived for inhalation exposure.
4. Long-term exposure-dermal route:
4.1 Long-term exposure-systemic effects/dermal route:
No repeated dose toxicity by the dermal route is available. However, no evidence of systemic toxicity was observed in the acute dermal toxicity (Tuffnell, 1992). There was systemic toxicity identified at the maximal dose tested in the repeated dose study by the oral route,There was a dose-related decrease in body weights and body weight gains in males at all doses which reached statistical significance at 1000 mg/kg/day. At necropsy, test item-related lower mean body weights were noted in males treated at 1000 mg/kg/day. Macroscopic test item-related abnormal growth or irregular color of lower incisor teeth was observed in some males and females treated at 1000 mg/kg/day. The NOAEL /oral/rat = 300 mg/kg bw/day can be considered for a route to route extrapolation to derive a DNEL for inhalation route.The following Table indicates the dermal DNEL for systemic toxicity calculation
Table 4.1/1 DNEL calculation for long-term exposure by dermal route:
General population |
Systemic long-term DNEL |
Step a: determination of the critical dose |
|
Key study |
Parr (2014).OECD 408, tested doses: 0, 100, 300 and 1000 mg/kg b.w/day (Kr: 1). |
Relevant dose descriptor |
NOAEL/oral/rat (males and females) = 300 mg/kg bw/day (worst case), ( a slight change in body weight, gross and microscopic findings in teeth at the highest tested dose )
|
Etape b : Correct starting point-factor and route to route extrapolation |
|
Dermal NAEL(corrected) |
NOAEL oral-rat/1 = 300 mg/kg bw/d (On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral to dermal extrapolation) |
Interspecies differences : - allometric scaling for metabolic rate - remaining differences (toxicokinetics andtoxicodynamics) |
4 (rat)
2,5 |
Intraspecies differences |
10(General population)
|
Duration extrapolation
|
2 (sub-acute to chronic extrapolation) |
Issues related to dose-response |
1 (NOAEL (worst case)) |
Quality of whole database |
1 |
Overall assessment factor |
200 |
DNEL Long-term by dermal route proposed(mg/kg bw/day) |
1,5 |
The Dermal DNEL long-term for systemic effects is = 1,5 mg/kg bw/day in the general public. However, no long-term dermal exposure is expected at this high level based on the precautions taken to prevent skin sensitisation effects.
4.2 Long-term exposure-local effects/dermal route:
The sensititisation study was conducted according to the Guinea-Pig Maximisation test (see section 7.4) ans showed positive results for the ITC 288/S. Considering these data, it is very difficult to derive a threshold and to set a DNEL. Hence, only qualitative assessment can be performed following the approach described in the dossier to define the risk management measures (RMMs) and operational conditions (OCs), (R8 -10, p125).
5. Long-term exposure-oral route:
5.1 Long-term exposure-systemic effects/oral route:
One study is available as a OECD 408 compliant GLP study (Parr, 2014).
Table 5.1/1 DNEL calculation for long-term exposure by oral route:
General population |
Systemic long-term DNEL |
Step a: determination of the critical dose |
|
Key study |
Parr (2014).OECD 408, tested doses: 0, 100, 300 and 1000 mg/kg b.w/day (Kr: 1) |
Relevant dose descriptor |
NOAEL/oral/rat (males and females) = 300 mg/kg bw/day, (worst case), (a slight change in body weight, gross and microscopic findings in teeth at the highest tested dose) |
Step c : assessment factors |
|
Interspecies differences (rat/human) |
4x1* |
Intraspecies differences (General population) |
10 |
Duration extrapolation (sub-chronic to chronic) |
2 |
Remaining differences |
2,5 |
Study quality |
1 |
Overall assessment factor |
200 |
DNEL Long-term by oral route proposed (mg/kg b.w/day) |
1,5 |
The Oral DNEL long-term for systemic effects is = 1,5 mg/kg bw/day in the general public.
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.