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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
1.23 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
30.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 25 mg/kg bw /day was determined for the registered substance in an oral sub-chronic toxicity study in rats (OECD TG 408, GLP).

This value was converted into the corrected inhalatory NOAEC taking into account the standard respiratory factor of 1/0.38 m³/kg/day, the absorption rates (based on ECHA Guidance R.8 the absorption rate of the starting route is by the factor of 2 lower than the one of the end-route in case of route to route extrapolation from oral to inhalation) and the standard respiratory volume in humans/ worker respiratory volume (6.7 m³ (8 h) / 10 m³ (8 h)) and the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4.

NOAEC corrected = 25 mg/kg bw/day * 1/0.38 m³/kg/day * 0.5 * (6.7 m³/10 m³) * 1.4 = 30.8 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
39.2 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
125
Dose descriptor starting point:
other: LD0
Value:
175 mg/kg bw/day
Modified dose descriptor starting point:
other: LC0
Value:
4 900 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is experimental data for acute toxicity by the oral and inhalatory route. The acute DNEL is derived from the acute oral and acute inhalation toxicity study. The most conservative DNEL is then selected.

Oral acute toxicity as starting point

The oral LD0 of 175 mg/kg bw was converted into a corrected inhalatory LC0 taking into account the standard respiratory factor for 15 min of 1/0.012 m³/kg (0.0008 m³/min/kg bw * 15 min), the absorption rates (oral 50 %, inhalation 100 %) and the standard respiratory volume in humans/ worker respiratory volume (0.21 m³/person in 15 min / 0.3125 m³ (15 min)). For details on underlying assumtions and calculations see below.

Guidance R8 Table R8 -2:

Respiratory volume (standard) in rat : 0.8 L/min/kg bw converted to 0.0008 m³/min/kg

Respriatory volume (standard) in human, 8h: 6.7 m³/person / 480 (8h * 60 min) *15 min; Respiratory volume light acitvity 8h: 10m³/person / 480 (8h*60min) *15 min

LC0 corrected = 175 mg/kg bw * 1/(0.012 m³/kg) * 50/100 * (0.21 m³/0.3125 m³) = 4900 mg/m³

Inhalation acute toxicity as starting point

The inhalative LC0 of 5220.8 mg/m³ was converted into a corrected inhalatory LC0 by applying the Haber's Law to correct for the study duration.

Haber's Law: Cn * t = k,

where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant; a default value of n=3 for extrapolating from longer to shorter exposure durations is used.

(C³ x t) = (C') ³ x t', giving C' = C x (t/t')0.333333. C' is the sought concentration. C' = 5220.8 mg/m³ x (4h/0.25h)0.3333333 = 13155.6 mg/m³. The concentration of 13155.6 mg/m³ was adjusted for the differences in the respiratory rates by normal conditions and by light activity: 0.21 m³/0.3125 m³

LC0 corrected = 13155.6 mg/m³ * 0.21 m³/0.3125 m³ = 8770.4 mg/m³

AF for dose response relationship:
10
Justification:
The LC0 is considered as LOAEC. To account for the uncertainties for the use of an acute toxicity study to derive a NOAEC the highest assessment factor of 10 for the LOAEL to NOAEL extrapolation proposed by the ECHA Guidance R.8 is used.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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):
100
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 25 mg/kg bw /day was determined for the registered substance in a sub-chronic oral toxicity study in rats (OECD TG 408, GLP). This value was converted into the corrected NOAEL taking into account the absorption rates (based on the physicochemical properties and toxicological profile of the registered substance, an oral absorption rate of 100 % and a dermal absorption rate of 10 % are assumed as worst-case assumptions) and the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4.

NOAEL corrected = 25 mg/kg bw/day * 100/10 * 1.4 = 350 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.218 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
10.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 25 mg/kg bw /day was determined for the registered substance in a sub-chronic oral toxicity study in rats (OECD TG 408, GLP).

This value was converted into the corrected inhalatory NOAEC taking into account the standard respiratory factor of 1/1.15 m³/kg/day and the absorption rates (based on ECHA Guidance R.8 the absorption rate of the starting route is by the factor of 2 lower than the one of the end-route in case of route to route extrapolation from oral to inhalation).

NOAEC corrected = 25 mg/kg bw/day * 1/1.15 m³/kg/day * 0.5 = 10.9 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29.2 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
250
Dose descriptor starting point:
other: LD0
Value:
175 mg/kg bw/day
Modified dose descriptor starting point:
other: LC0
Value:
7 291.67 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is experimental data for acute toxicity by the oral and inhalatory route. The acute DNEL was derived from the acute oral and acute inhalation toxicity study. The most conservative DNEL is then selected.

Oral acute toxicity as starting point

The oral LD0 of 175 mg/kg bw was converted into a corrected inhalatory LC0 taking into account the standard respiratory factor for 15 min of 1/0.012 m³/kg (0.0008 m³/min/kg bw * 15 min) and the absorption rates (oral 50 %, inhalation 100 %).  For details on underlying assumtions and calculations see below.

Guidance R8 Table R8 -2:

Respiratory volume (standard) in rat : 0.8 L/min/kg bw converted to 0.0008 m³/min/kg

Respriatory volume (standard) in human, 8h: 6.7 m³/person / 480 (8h * 60 min) *15 min;

LC0 corrected = 175 mg/kg bw * 1/0.012 m³/kg * 50/100 = 7291.67 mg/m³

Inhalation acute toxicity as starting point

The inhalative LC0 of 5220.8 mg/m³ was converted into a corrected inhalatory LC0 by applying the Haber's Law to correct for the study duration.

Haber's Law: Cn * t = k,

where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant; a default value of n=3 for extrapolating from longer to shorter exposure durations is used.

(C³ x t) = (C') ³ x t', giving C' = C x (t/t')0.333333. C' is the sought concentration. C' = 5220.8 mg/m³ x (4h/0.25h)0.3333333 = 13155.6 mg/m³.

LC0 corrected = 13155.6 mg/m³

AF for dose response relationship:
10
Justification:
The LC0 is considered as LOAEC. To account for the uncertainties for the use of an acute toxicity study to derive a NOAEC the highest assessment factor of 10 for the LOAEL to NOAEL extrapolation proposed by the ECHA Guidance R.8 is used.
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database

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:
1.25 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 25 mg/kg bw /day was determined for the registered substance ina sub-chronic oral toxicity study in rats (OECD TG 408, GLP). This value was converted into the corrected NOAEL taking into account the absorption rates (based on the physicochemical properties and toxicological profile of the registered substance, an oral absorption rate of 100 % and a dermal absorption rate of 10 % are assumed as worst-case assumptions).

NOAEL corrected = 25 mg/kg bw/day * 100/10 = 250 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.125 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 25 mg/kg bw /day was determined for the registered substance in a sub-chronic oral toxicity study in rats (OECD TG 408, GLP).

This value does not have to be corrected as the oral absorption rate of rats and humans are considered to be identical (100 % as worst-case assumption).

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.625 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population