Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
37 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance with modified AF for differences in duration of exposure
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 850 mg/m³
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected inhalatory No-Observed-Adverse-Effect-Concentration (NOAEC) is a No-Observed-Adverse-Effect-Level (NOAEL) of 1000 mg/kg bw/day as determined in an oral combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in the rat. Corrections for differences in respiratory volumes of laboratory animals and workers (1/0.38 = 2.63), for the respiratory volume in light activity (6.7/10 = 0.67), for the frequency of exposure (7/5 = 1.4) as well as for inhalative and oral bioavailability (0.75) were accounted for.

Corrected inhalatory NOAEC = NOAELoral, rat x (1/sRVrat) x (sRVhuman/wRV) x (ABSoral, rat/ABSinhal., human) x (fexpo, rat/fexpo, worker)

sRV: Standard respiratory volume

wRV: Respiratory volume of workers (8 h)

ABS: Absorption rate (oral absorption is assumed to be 75% of inhalation absorption as default)

fexpo: Frequency of exposure (rat: 7 days/week; workers: 5 days/week)

Corrected inhalatory NOAEC = 1000 x 2.63 x 0.67 x 0.75 x 1.4 = 1850 mg/m3

AF for dose response relationship:
1
Justification:
Default (DNEL calculator), starting point is NOAEL or NOAEC
AF for differences in duration of exposure:
4
Justification:
ECHA default assessment factor (AF) for extrapolation subchronic (90-day) to chronic: 2; ECHA default AF for extrapolation subacute (28-day) to chronic: 6
Dosing duration in OECD 422 study used as basis for DNEL calculation: Males: 29 - 35 days; Females that delivered: 50 - 64 days; Females that failed to deliver: 41 -42 days.
Since most of the test animals were dosed for > 50 days (females that delivered), scaling of the AF for differences in exposure duration is justified.
Scaled AF: (50/28) x 2 = 1.8 x 2 = 3.6. Therefore, an AF of 4 is considered conservative enough to reflect the acutal dosing situation in the OECD 422 study used as basis for the DNEL calculation.
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator), not relevant for inhalatory exposure as already considered in species-specific respiratory volumes
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator), workers
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator), high quality study used to calculate DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
350 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance with modified AF for differences in duration of exposure
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
70 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected dermal No-Observed-Adverse-Effect-Level (NOAEL) is a NOAEL of 1000 mg/kg bw/day as determined in an oral combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in the rat. Corrections for dermal and oral bioavailability (50.0) and differences in the frequency of exposure (7/5 = 1.4) were accounted for.

Corrected dermal NOAEL = NOAELoral, rat x (ABSoral, rat/ABSdermal, human) x (fexpo, rat/fexpo, worker)

ABS: Absorption rate (absorption rate in humans established to be 2%; correction of oral (rat) and dermal (human) bioavailability: 1/0.02 = 50.0)

fexpo: Frequency of exposure (rat: 7 days/week; workers: 5 days/week)

Corrected dermal NOAEL = 1000 x 50.0 x 1.4 = 70000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default (DNEL calculator), starting point is NOAEL or NOAEC
AF for differences in duration of exposure:
4
Justification:
ECHA default assessment factor (AF) for extrapolation subchronic (90-day) to chronic: 2; ECHA default AF for extrapolation subacute (28-day) to chronic: 6
Dosing duration in OECD 422 study used as basis for DNEL calculation: Males: 29 - 35 days; Females that delivered: 50 - 64 days; Females that failed to deliver: 41 -42 days.
Since most of the test animals were dosed for > 50 days (females that delivered), scaling of the AF for differences in exposure duration is justified.
Scaled AF: (50/28) x 2 = 1.8 x 2 = 3.6. Therefore, an AF of 4 is considered conservative enough to reflect the acutal dosing situation in the OECD 422 study used as basis for the DNEL calculation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator), rat
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator), workers
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator), high quality study used to calculate DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.53 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance with modified AF for differences in duration of exposure
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
653 mg/m³
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected inhalatory No-Observed-Adverse-Effect-Concentration (NOAEC) is a No-Observed-Adverse-Effect-Level (NOAEL) of 1000 mg/kg bw/day as determined in an oral combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in the rat. Corrections for differences in respiratory volumes of laboratory animals and the general population (1/1.15 = 0.87) and for inhalative and oral bioavailability (0.75) were accounted for.

Corrected inhalatory NOAEC = NOAELoral, rat x (1/sRVrat) x (ABSoral, rat/ABSinhal., human)

sRV: Standard respiratory volume

ABS: Absorption rate (oral absorption is assumed to be 75% of inhalation absorption as default)

Corrected inhalatory NOAEC = 1000 x 0.87 x 0.75 = 653 mg/m3

AF for dose response relationship:
1
Justification:
Default (DNEL calculator), starting point is NOAEL or NOAEC
AF for differences in duration of exposure:
4
Justification:
ECHA default assessment factor (AF) for extrapolation subchronic (90-day) to chronic: 2; ECHA default AF for extrapolation subacute (28-day) to chronic: 6
Dosing duration in OECD 422 study used as basis for DNEL calculation: Males: 29 - 35 days; Females that delivered: 50 - 64 days; Females that failed to deliver: 41 -42 days.
Since most of the test animals were dosed for > 50 days (females that delivered), scaling of the AF for differences in exposure duration is justified.
Scaled AF: (50/28) x 2 = 1.8 x 2 = 3.6. Therefore, an AF of 4 is considered conservative enough to reflect the acutal dosing situation in the OECD 422 study used as basis for the DNEL calculation.
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator), not relevant for inhalatory exposure as already considered in species-specific respiratory volumes
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator), general population
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator), high quality study used to calculate DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
125 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance with modified AF for differences in duration of exposure
Overall assessment factor (AF):
400
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected dermal No-Observed-Adverse-Effect-Level (NOAEL) is a NOAEL of 1000 mg/kg bw/day as determined in an oral combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in the rat. A correction for dermal and oral bioavailability (50.0) was accounted for.

Corrected dermal NOAEL = NOAELoral, rat x (ABSoral, rat/ABSdermal, human)

ABS: Absorption rate (absorption rate in humans established to be 2%; correction of oral (rat) and dermal (human) bioavailability: 1/0.02 = 50.0)

Corrected dermal NOAEL = 1000 x 50.0 = 50000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default (DNEL calculator), starting point is NOAEL or NOAEC
AF for differences in duration of exposure:
4
Justification:
ECHA default assessment factor (AF) for extrapolation subchronic (90-day) to chronic: 2; ECHA default AF for extrapolation subacute (28-day) to chronic: 6
Dosing duration in OECD 422 study used as basis for DNEL calculation: Males: 29 - 35 days; Females that delivered: 50 - 64 days; Females that failed to deliver: 41 -42 days.
Since most of the test animals were dosed for > 50 days (females that delivered), scaling of the AF for differences in exposure duration is justified.
Scaled AF: (50/28) x 2 = 1.8 x 2 = 3.6. Therefore, an AF of 4 is considered conservative enough to reflect the acutal dosing situation in the OECD 422 study used as basis for the DNEL calculation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator), rat
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator), general population
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator), high quality study used to calculate DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance with modified AF for differences in duration of exposure
Overall assessment factor (AF):
400
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
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required as the oral long-term DNEL for systemic effects is based on a No-Observed-Adverse-Effect-Level (NOAEL) of 1000 mg/kg bw/day as determined in an oral combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in the rat.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator), starting point is NOAEL or NOAEC
AF for differences in duration of exposure:
4
Justification:
ECHA default assessment factor (AF) for extrapolation subchronic (90-day) to chronic: 2; ECHA default AF for extrapolation subacute (28-day) to chronic: 6
Dosing duration in OECD 422 study used as basis for DNEL calculation: Males: 29 - 35 days; Females that delivered: 50 - 64 days; Females that failed to deliver: 41 -42 days.
Since most of the test animals were dosed for > 50 days (females that delivered), scaling of the AF for differences in exposure duration is justified.
Scaled AF: (50/28) x 2 = 1.8 x 2 = 3.6. Therefore, an AF of 4 is considered conservative enough to reflect the acutal dosing situation in the OECD 422 study used as basis for the DNEL calculation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator), rat
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator), general population
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator), high quality study used to calculate DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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