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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.5 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 234 mg/m³
Explanation for the modification of the dose descriptor starting point:

No repeated dose inhalation toxicity study is available. Therefore, the DNEL is derived on basis of an OECD TG 422 toxicity study performed in the rat. This oral NOAEL of 1000 mg/kg bw/day for rats was converted to the corresponding air concentration using a standard breathing volume for the rat of 0.38 m³ /kg (for 8 hours exposure of workers). The resulting air concentration was additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). See "Additional Information" for more details.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default assessment factor for subacute to chronic duration extrapolation is used.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The study according to OECD TG 422 was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
4.7 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default assessment factor for subacute to chronic duration extrapolation is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The study according to OECD TG 422 was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

Inhalation

Long term, systemic DNEL – exposure via inhalation (workers)

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is calculated. This worker long-term DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

No repeated dose inhalation toxicity study with the target substance is available. Therefore, it is necessary to obtain a long-term DNEL by route-to-route extrapolation:

An OECD TG 422 study with the target substance is available. Here, daily oral administration of the test item to Wistar rats did not elicit any signs of systemic, reproductive and developmental toxicity up to the highest dose tested. The NOAEL for systemic toxicity, developmental toxicity and fertility was considered to be 1000 mg/kg bw/day. This NOAEL is used as Point of Departure (PoD) for DNEL derivation.

Step 1: PoD: NOAEL = 1000 mg/kg bw/day

Step 2: Modification of PoD:

Standard respiratory volume, human (sRVhuman): 6.7 m³

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human):50 %/100 % (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

= 1000 mg/kg bw/day x 0.5 x 1/0.38 m³/kg bw/day x (6.7 m³/10 m³) x (7/5)

= 1234 mg/m³

Step 3: Overall AF= 75

Intraspecies AF (workers): 5

Interspecies AF, remaining differences: 2.5

Interspecies, allometric scaling: 1 (Covered by route to route extrapolation)

Dose response relationship AF: 1

Exposure duration AF: 6

Whole database AF: 1

In conclusion, long term systemic inhalation DNEL, workers = 16.5 mg/m^3

Acute, systemic DNEL- exposure via inhalation (workers)

There is no short-term or long-term toxicity study via inhalation route available for the test substance.

As the substance is not classified for acute oral toxicity, no effects for acute inhalation are expected, therefore no DNEL was derived.

Long term & acute, local DNEL- exposure via inhalation (workers)

A DNEL long term & acute - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.Therefore, no local irritation or sensitisation of the respiratory system is expected.

Dermal

Long term, systemic DNEL- exposure via dermal route (workers)

No repeated dose dermal toxicity study with the target substance is available. Therefore, it is necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.

The NOAEL of 1000 mg/kg bw/day derived from an OECD TG 422 study performed with the target was used as the PoD.

Step 1: PoD: NOAEL = 1000 mg/kg bw/day

Step 2: Modification into a correct starting point:

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

= 1000 mg/kg bw/day x (7/5)

= 1400 mg/kg bw/day

Step 3: Overall AF= 300

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Dose-response relationship AF: 1

Exposure duration AF: 6

Whole database AF: 1

In conclusion, long term systemic dermal DNEL, workers = 4.7 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (workers)

A DNEL for acute systemic-dermal exposure was not derived since the substance is not classified for oral acute toxicity and in in-vivo studies using dermal application (skin sensitization) no systemic effects were observed.

Long term & acute, local DNEL- dermal exposure (workers)

DNELs for long term & acute - local effects are not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.

Hazard to the eye-local effects (workers)

The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP). Therefore, no hazard has been identified.

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:

Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

No repeated dose inhalation toxicity study is available. The DNEL is derived on basis of an OECD TG 422 study. This oral NOAEL for rats was converted to the corresponding air concentration using a standard breathing volume for the rat of 1.15 m³/kg for 24 hours exposure, and assuming a two-times higher absorption via inhalation than oral absorption (see "Additional Information").

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default assessment factor for subacute to chronic duration extrapolation is used.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The study according OECD TG 422 was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.7 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default assessment factor for subacute to chronic duration extrapolation is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The OECD TG 422 toxicity study performed with the test item was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.7 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default assessment factor for subacute to chronic duration extrapolation is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The study according OECD TG 422 was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

Inhalation

Long term, systemic DNEL – exposure by inhalation (general population)

No repeated dose inhalation toxicity study with the target substance is available. Therefore, it is necessary to obtain a long-term DNEL by route-to-route extrapolation:

An OECD TG 422 study with the target substance is available. Here, daily oral administration of the test item to Wistar rats did not elicit any signs of systemic, reproductive and developmental toxicity up to the highest dose tested. The NOAEL for systemic toxicity, developmental toxicity and fertility was considered to be 1000 mg/kg bw/day. This NOAEL is used as PoD for DNEL derivation.

Step 1: PoD: NOAEL = 1000 mg/kg bw/day

Correction for difference between human and experimental exposure conditions: 7 d rat, 24 h / 7 d, 24 h general population

Step 2: Modification of PoD:

Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m³/kg bw

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50 %/100 % (default)

Corrected NOAEC (inhalation) for general population:

= 1000 mg/kg bw/day x 0.5 x 1/1.15 m³/kg bw/day

= 434.8 mg/m³

Step 3: Overall AF= 150

Intraspecies AF (General population): 10

Interspecies AF, remaining differences: 2.5

Interspecies, allometric scaling: 1

Dose response relationship AF: 1

Exposure duration AF: 6

Whole database AF: 1

In conclusion, long term systemic inhalation DNEL, general population = 2.9 mg/m³

Acute, systemic DNEL- exposure via inhalation (general population)

There is no short-term or long-term toxicity study via inhalation route available for the test substance.

As the substance is not classified for acute oral toxicity, no effects for acute inhalation are expected, therefore no DNEL was derived.

Long term, local DNEL- exposure via inhalation (general population)

A DNEL long term & acute - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008. Therefore, no local irritation or sensitisation of the respiratory system is expected.

Dermal

Long term, systemic DNEL- exposure via dermal route (general population)

No repeated dose dermal toxicity study with the target substance is available. Therefore, it is necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.

The NOAEL of 1000 mg/kg bw/day derived from an OECD TG 422 study performed with the target substance was used as the PoD.

Step 1: PoD: NOAEL= 1000 mg/kg bw/day

Oral absorption of the rat/ dermal absorption of humans (ABS oral-rat / ABS dermal-human): 100 %/ 100 % (default)

Correction for difference between human and experimental exposure conditions: 7 d rat, 24 h/7 d, 24h general population

Step 2: Overall AF= 600

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Dose-response relationship AF: 1

Exposure duration AF: 6

Whole database AF: 1

In conclusion, long term systemic dermal DNEL, general population = 1.7 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (general population)

A DNEL for acute systemic-dermal exposure was not derived since the substance is not classified for oral acute toxicity and in in-vivo studies using dermal application (skin sensitization) no systemic effects were observed.

Long term & acute, local DNEL- dermal exposure (general population)

DNELs for long term & acute - local effects are not established because the substance is not classified dangerous for skin irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.

Oral

Long term, systemic DNEL- exposure by oral route (general population)

A study according OECD TG 422 with the target substance is available. Here, daily oral administration of the test item to Wistar rats did not elicit any signs of systemic, reproductive or developmental toxicity up to the highest dose tested. The NOAEL for systemic toxicity, developmental toxicity and fertility was considered to be 1000 mg/kg bw/day. This NOAEL is used as PoD for DNEL derivation.

Step 1: PoD: NOAEL = 1000 mg/kg bw/day

No modifications were done as same exposure route is considered.

Step 2: Overall AF= 600

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Dose-response relationship AF: 1

Exposure duration AF: 6

Whole database AF: 1

In conclusion, long term systemic oral DNEL, general population= 1.7 mg/kg bw/day

Acute, systemic DNEL- exposure by oral route (general population)

According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, „a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute oral toxicity with the LD50 of >2000 mg/kg. Therefore, the DNEL is not required.

Hazard to the eye-local effects (general population)

The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP).

 

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:

Characterization of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterization, Version 3.0, May 2016