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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

In a GLP-compliant guideline 90-day oral study with rats, combined with reproductive/developmental toxicity screening, the lowest tested level of 1 mg/kg bw/day was considered to be a LOAEL, based on the presence of granulomatous inflammation of the mesenteric lymph nodes with central necrosis at all dose levels with dose-related increase in severity.

The corrected 8 hr inhalation LOAEC for workers is LOAEL(1 mg/kg) * 1/0.38 * 6.7/10(light exercise) * 5/7(correction dosing 7days/wk) = 1,234 mg/m3.

Additionally, the default factor of 2 to address uncertainty with respect to possible differences in absorption between inhalation and oral route has been applied.

AF for dose response relationship:
3
Justification:
Extrapolation from LOAEL to NOAEL. The severity of the foamy macrophages in the mesenteric lymph nodes at 1 mg/kg bw is at the high end of what sometimes is seen in control groups. However, in three animals the observed minimal to slight central necrosis is considered adverse. But further extrapolation with a factor 3 to dose levels of 0.33 mg/kg bw/d, would indicate a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
4.67 µg/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:
LOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a GLP-compliant guideline 90-day oral study with rats, combined with reproductive/developmental toxicity screening, the lowest tested level of 1 mg/kg bw/day was considered to be a LOAEL, based on the presence of granulomatous inflammation of the mesenteric lymph nodes with central necrosis at all dose levels with dose-related increase in severity.

The corrected 8 hr dermal LOAEL for workers is LOAEL(1 mg/kg) * 5/7(correction dosing 7days/wk) = 1.4 mg/kg bw/day.

AF for dose response relationship:
3
Justification:
Extrapolation from LOAEL to NOAEL. The severity of the foamy macrophages in the mesenteric lymph nodes at 1 mg/kg bw is at the high end of what sometimes is seen in control groups. However, in three animals the observed minimal to slight central necrosis is considered adverse. But further extrapolation with a factor 3 to dose levels of 0.33 mg/kg bw/d, would indicate a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

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:
2.47 µg/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:
LOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
0.37 mg/m³
Explanation for the modification of the dose descriptor starting point:

In a GLP-compliant guideline 90-day oral study with rats, combined with reproductive/developmental toxicity screening, the lowest tested level of 1 mg/kg bw/day was considered to be a LOAEL, based on the presence of granulomatous inflammation of the mesenteric lymph nodes with central necrosis at all dose levels with dose-related increase in severity.

The corrected 24 hr inhalation LOAEC for general population is LOAEL(1 mg/kg) * 1/1.35 mg/m3 = 0.74 mg/m3. Subsequently, the default factor 2 for route extrapolation from oral to inhalation has been applied resulting to a NOAEC for general population of 0.74 / 2 = 0.37 mg/m3.

AF for dose response relationship:
3
Justification:
Extrapolation from LOAEL to NOAEL. The severity of the foamy macrophages in the mesenteric lymph nodes at 1 mg/kg bw is at the high end of what sometimes is seen in control groups. However, in three animals the observed minimal to slight central necrosis is considered adverse. But further extrapolation with a factor 3 to dose levels of 0.33 mg/kg bw/d, would indicate a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation.
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results
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:
1.67 µg/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:
LOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a GLP-compliant guideline 90-day oral study with rats, combined with reproductive/developmental toxicity screening, the lowest tested level of 1 mg/kg bw/day was considered to be a LOAEL, based on the presence of granulomatous inflammation of the mesenteric lymph nodes with central necrosis at all dose levels with dose-related increase in severity.

AF for dose response relationship:
3
Justification:
Extrapolation from LOAEL to NOAEL. The severity of the foamy macrophages in the mesenteric lymph nodes at 1 mg/kg bw is at the high end of what sometimes is seen in control groups. However, in three animals the observed minimal to slight central necrosis is considered adverse. But further extrapolation with a factor 3 to dose levels of 0.33 mg/kg bw/d, would indicate a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results.
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:
1.67 µg/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:
LOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a GLP-compliant guideline 90-day oral study with rats, combined with reproductive/developmental toxicity screening, the lowest tested level of 1 mg/kg bw/day was considered to be a LOAEL, based on the presence of granulomatous inflammation of the mesenteric lymph nodes with central necrosis at all dose levels with dose-related increase in severity. No modification for dose descriptor for route to route extrapolation is needed.

AF for dose response relationship:
3
Justification:
Extrapolation from LOAEL to NOAEL. The severity of the foamy macrophages in the mesenteric lymph nodes at 1 mg/kg bw is at the high end of what sometimes is seen in control groups. However, in three animals the observed minimal to slight central necrosis is considered adverse. But further extrapolation with a factor 3 to dose levels of 0.33 mg/kg bw/d, would indicate a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results
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

No exposure of the general population to Diamine methylated is foreseen based on the uses indicated in this dossier that are limited to industrial use as intermediate.

However, to allow for evaluation from indirect exposures via the environment, DNELs have been derived for systemic toxicity from long term exposures via all routes.