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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
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.
Diss Factsheets
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EC number: 200-554-5 | CAS number: 63-05-8
- 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:
- 176 µg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 4.41 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The leading health effect after repeated exposure is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to inhalation is possible. The default assumption for differences in bioavailability between the two exposure routes (50 % of the substance will be absorbed after oral compared to inhalation exposure) is employed in this extrapolation. Further uncertainties related to toxicokinetics were taken into account by the factor 2.5 for remaining interspecies uncertainties.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already covered with correction of dose-descriptor.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 5
- Justification:
- For intraspecies variability, the default assessment factor for workers is 5.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 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:
- 50 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- 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:
- 5 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- For androstendione it is not indicated that dermal absorption is higher than oral absorption, since at least acute toxicity studies reveal no findings at all after dermal exposure compared to unspecific and slight findings after oral exposure. Moreover, the leading health effect after repeated exposure is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to dermal route is justified.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- For allometric scaling rat to human the standard factor is 4
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 5
- Justification:
- For intraspecies variability, the default assessment factor for workers is 5.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 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
Andostendione is an endogenous intermediate in steroid hormone synthesis and as such an endogenous precursor of testosterone and estrone, which can be metabolized to estradiol. Consequently, repeated exposure to the substance interferes with the body's hormonal balance (For a discussion on health effects see FDA white paper, Health Effects of Androstendione, 2004).
Subchronic (90-day) animal studies revealed evidence that the effect on fertility is the leading health effect of androstendione (NTP Technical Report 560, NIH Publication No. 10-5901, 2010). The single dermal exposure to the substance at 2000 mg/kg was tolerated without any findings (Schering, 1995), whereas the single oral exposure of 500 mg/kg led to unspecific and slight effects (LD50 > 500 and < 1000 mg/kg; Schering, 1989, 1994). No potential for skin or eye irritation or skin sensitization was concluded based on experimental studies (Schering AG, 1987 and 1995). For androstendione two carcinogenicity studies were available (NTP Technical Report 560, NIH Publication No. 10-5901, September 2010). The one on rats showed equivocal evidence and the one on mice clear evidence for carcinogenic activity. However, it has to be taken into account that steroid hormones in general can promote the growth of specific hormone dependent tissues and tumors. Furthermore, the overall conclusion of the available genotoxicity studies support that androstendione does not act as genotoxic carcinogen (Ames neg., Cytotest Cell Research GmbH, 1996; HPRT neg., Harlan Cytotest Cell Research GmbH, 2013; MNT in vivo, rat - neg., male mouse - neg, female mouse - equivocal, see NTP Technical Report 560, NIH Publication No. 10-5901, 2010). Therefore, despite the evidence of carcinogenic activity a threshold effect is concluded for androstendione and this threshold has to be related to reproductive toxicity/fertility. Consequently, for workers DNELs for long term exposure via inhalation and dermal route have to be derived.
The two available subchronic (90-day) studies that confirmed the effect on fertility as the leading health effect after repeated oral exposure were on rats and mice (NTP Technical Report 560, NIH Publication No. 10-5901, 2010). Whereas the rat study revealed a NOAEL of 5 mg/kg (based on sperm investigations; decreased number of sperm), mice were shown to be less susceptiple to reproductive toxicity of androstendione (based on sperm investigations; decreased sperm motility at 50 mg/kg). Therefore the NOAEL of the rat study was used as point of departure for the delineation of the NOAEL.
DNELsystemic, long-term for workers for hazard via inhalation route:
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 3, Guidance Document R.8, ECHA, 2012):
In case of workers 8h/day exposed:
corrected inhalatory NOAEC =oral NOAEL * sRVrat-1* ABSoral-rat/ABSinh-human* sRVhuman/wRV
= oral NOAEL * (0.38 m³/kg bw)-1* 0.5 * 0.67 = 4.41 mg/m³
sRVrat= default respiratory volume rat, 8 h exposure = 0.38 m³/kg bw
ABSoral-rat/ABSinh-human= the absorption of rats after oral exposure is assumed to be 50 % of the human absorption after inhalation = 0.5
sRVhuman= standard respiratory volume human, 8 h exposure = 6.7 m³/person
wRV = respiratory volume light activity for worker, 8 h exposure = 10 m³/person
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the corrected NOAEC and are summarized in the table below:
Assessment | Assessment Factor
|
For interspecies differences rat vs. human (allometric scaling) | Already covered with correction of dose-descriptor |
1For remaining interspecies differences | 2.5 |
2For intraspecies differences (workers) | 5 |
3Differences in duration of exposure | 2 |
4Dose-response relationship | 1 |
5Quality of whole Database | 1 |
Overall Assessment Factor | 25 |
1A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
2For intraspecies variability, the default assessment factor for workers is 5.
3The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
4When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
5The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore the overall AF (assessment factor) is 25. Corrected inhalatory NOAEC : 25 = 0.176 mg/m³ = 176 µg/m³
DNELsystemic, long-term for workers for hazards via inhalation route = 176 µg/m³
DNELsystemic, long-term for workers for hazard via dermal route:
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 5, Guidance Document R.8, ECHA, 2012):
In case of workers 8h/day exposed:
corrected dermal NOAEL = oral NOAEL * ABSoral-rat/ABSdermal-human = oral NOAEL * 1 = 5 mg/kg
ABSoral-rat/ABSdermal-human= the absorption of rats after oral exposure is assumed to be identical to the absorption of humans after dermal exposure = 1
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the NOAEL and are summarized in the table below:
Assessment | Assessment Factor
|
1For interspecies differences rat vs. human (allometric scaling) | 4 |
2For remaining interspecies differences | 2.5 |
3For intraspecies differences (workers) | 5 |
4Differences in duration of exposure | 2 |
5Dose-response relationship | 1 |
6Quality of whole Database | 1 |
Overall Assessment Factor | 100 |
1For allometric scaling rat to human the standard factor is 4.
2A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
3For intraspecies variability, the default assessment factor for workers is 5.
4The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
5When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
6The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore the overall AF (assessment factor) is 100. Corrected dermal NOAEL : 100 = 0.05 mg/kg = 50 µg/kg
DNELsystemic, long-term for workers for hazards via dermal route = 50 µg/kg bw/day.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 43 µg/m³
- Most sensitive endpoint:
- effect on fertility
- 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:
- 5 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 2.17 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The leading health effect after repeated exposure is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to inhalation is possible. The default assumption for differences in bioavailability between the two exposure routes (50 % of the substance will be absorbed after oral compared to inhalation exposure) is employed in this extrapolation. Further uncertainties related to toxicokinetics were taken into account by the factor 2.5 for remaining interspecies uncertainties.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already covered with correction of dose-descriptor.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 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
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 25 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- 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:
- 5 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- For androstendione it is not indicated that dermal absorption is higher than oral absorption, since at least acute toxicity studies reveal no findings at all after dermal exposure compared to unspecific and slight findings after oral exposure. Moreover, the leading health effect after repeated exposure is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to dermal route is justified.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- For allometric scaling rat to human the standard factor is 4
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 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:
- 25 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- 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:
- 5 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- For allometric scaling rat to human the standard factor is 4
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 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
Andostendione is an endogenous intermediate in steroid hormone synthesis and as such an endogenous precursor of testosterone and estrone, which can be metabolized to estradiol. Consequently, repeated exposure to the substance interferes with the body¿s hormonal balance (For a discussion on health effects see FDA white paper, Health Effects of Androstendione, 2004).
Subchronic (90-day) animal studies revealed evidence that the effect on fertility is the leading health effect of androstendione (NTP Technical Report 560, NIH Publication No. 10-5901, 2010). The single dermal exposure to the substance at 2000 mg/kg was tolerated without any findings (Schering, 1995), whereas the single oral exposure of 500 mg/kg led to unspecific and slight effects (LD50 > 500 and < 1000 mg/kg; Schering, 1989, 1994). No potential for skin or eye irritation or skin sensitization was concluded based on experimental studies (Schering AG, 1987 and 1995). For androstendione two carcinogenicity studies were available (NTP Technical Report 560, NIH Publication No. 10-5901, September 2010). The one on rats showed equivocal evidence and the one on mice clear evidence for carcinogenic activity. However, it has to be taken into account that steroid hormones in general can promote the growth of specific hormone dependent tissues and tumors. Furthermore, the overall conclusion of the available genotoxicity studies support that androstendione does not act as genotoxic carcinogen (Ames neg., Cytotest Cell Research GmbH, 1996; HPRT neg., Harlan Cytotest Cell Research GmbH, 2013; MNT in vivo, rat - neg., male mouse - neg, female mouse - equivocal, see NTP Technical Report 560, NIH Publication No. 10-5901, 2010). Therefore, despite the evidence of carcinogenic activity a threshold effect is concluded for androstendione and this threshold has to be related to reproductive toxicity/fertility. Consequently, for the general population DNELs for long term exposure via inhalation/dermal/oral route have to be derived.
The two available subchronic (90-day) studies that confirmed the effect on fertility as the leading health effect after repeated oral exposure were on rats and mice (NTP Technical Report 560, NIH Publication No. 10-5901, 2010). Whereas the rat study revealed a NOAEL of 5 mg/kg (based on sperm investigations; decreased number of sperm), mice were shown to be less susceptiple to reproductive toxicity of androstendione (based on sperm investigations; decreased sperm motility at 50 mg/kg). Therefore the NOAEL of the rat study was used as point of departure for the delineation of the NOAEL.
DNELsystemic, long-term for the general population for hazard via inhalation route:
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 3, Guidance Document R.8, ECHA, 2012):
In case of the general population 24h/d exposed:
corrected inhalatory NOAEC =oral NOAEL * sRVrat-1* ABSoral-rat/ABSinh-human
=oral NOAEL * (1.15 m³/kg)-1* 0.5 = 2.17 mg/m³
sRVrat= default respiratory volume rat, 24 h exposure = 1.15 m³/kg
ABSoral-rat/ABSinh-human= the absorption of rats after oral exposure is assumed to be 50 % of the human absorption after inhalation = 0.5
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the corrected NOAEC and are summarized in the table below:
Assessment |
Assessment Factor
|
For interspecies differences rat vs. human (allometric scaling) |
Already covered with correction of dose-descriptor |
1For remaining interspecies differences |
2.5 |
2For intraspecies differences (general population) |
10 |
3Differences in duration of exposure |
2 |
4Dose-response relationship |
1 |
5Quality of whole Database |
1 |
Overall Assessment Factor |
50 |
1A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
2For intraspecies variability, the default assessment factor for the general population is 10.
3The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
4When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
5The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore the overall AF (assessment factor) is 50.Corrected inhalatory NOAEC : 50 = 0.043 mg/m³ = 43.5 µg/m³
DNELsystemic, long-term for workers for hazards via inhalation route = 43.5 µg/m³
DNELsystemic, long-term for the general population for hazard via dermal/oral route:
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 5, Guidance Document R.8, ECHA, 2012):
In case of the general population 24h/day exposed:
corrected dermal NOAEL = oral NOAEL * ABSoral-rat/ABSdermal-human= oral NOAEL * 1 = 5 mg/kg
ABSoral-rat/ABSdermal-human= the absorption of rats after oral exposure is assumed to be identical to the absorption of humans after dermal exposure = 1
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the NOAEL and are summarized in the table below:
Assessment |
Assessment Factor
|
1For interspecies differences rat vs. human (allometric scaling) |
4 |
2For remaining interspecies differences |
2.5 |
3For intraspecies differences (general population) |
10 |
4Differences in duration of exposure |
2 |
5Dose-response relationship |
1 |
6Quality of whole Database |
1 |
Overall Assessment Factor |
200 |
1For allometric scaling rat to human the standard factor is 4.
2A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
3For intraspecies variability, the default assessment factor for the general population is 10.
4The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
5When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
6The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore the overall AF (assessment factor) is 200. Corrected dermal NOAEL or oral NOAEL : 200 = 0.025 mg/kg = 25 µg/kg.
DNELsystemic, long-term for workers for hazards via dermal or oral route = 25 µg/kg bw/day.
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.